OPT101 Starts a Phase-II Clinical Trial

OPT101 is a small peptide (a type of protein) designed to target CD40, which plays a central role in the inflammatory autoimmune response that damages the insulin-producing beta cells in people with T1D.  The drug is given by subcutaneous injection, meaning it is injected just under the skin, like insulin.

The researchers hypothesize that by regulating inflammation related to CD40 immune cells (called Th40 cells), they can protect or restore the function of pancreatic beta cells, which would improve a person’s ability to produce their own insulin. 

The Study

This is a Phase 2, randomized, placebo-controlled trial testing the safety and early efficacy of OPT101. The study is not a single, uniform experiment, but is divided into three parts (A, B, and C).

Part A is an open-label phase where 18 adults will receive escalating doses of OPT101 (1.0, 1.5, or 2.0 mg/kg) three times a week for two weeks to evaluate tolerance and how the drug is processed by the body.   Parts B and C will be the core, placebo-controlled portions. In these parts, participants will be randomized to receive either the highest tolerated dose from Part A or a placebo for 48 weeks . The study plans to enroll a total of 72 participants across all parts.  In each group, twice as many people will get the treatment as get the placebo.

Everyone enrolled will be between 18 and 50 years old, but the time since diagnosis varies by part.  Part A allows diagnosis within the last 20 years, Part B is for people diagnosed between 1 and 10 years prior, and Part C is for those diagnosed within the last year.  So parts A and B include both honeymooners and people with established T1D, while part C only includes honeymooners.

The primary objective of the study is to measure the "Change in C-peptide" from baseline to the end of the 48-week treatment period. C-peptide is a direct and reliable indicator of a person's own insulin production. The secondary endpoints are designed to gather more detailed information and include measuring various pharmacokinetic parameters (i.e. to understand how the drug behaves in the body). 

The clinical trial officially began recruiting patients in April 2026, with a primary completion date estimated for May 2026 and a final study completion date in August 2028.

For people interested in learning more or potentially participating, the global contact for the study is Lisa Boswell, who can be reached by phone at 303-503-9954 or via email at lb@op-t.com.

The study is being conducted at several locations across the United States. The recruiting sites include the University of Alabama at Birmingham, the Diablo Clinical Research Center in California, the Barbara Davis Center at the University of Colorado Anschutz Medical Campus, the University of Chicago Medical Center, and the Rainier Clinical Research Center in Washington.

The trial is sponsored by Op-T LLC, the company developing OPT101.  Support for the research into OPT101's mechanism of action has also been provided by a grant from the National Institutes of Health (NIH).

Discussion

The previous Phase 1 trial, presented at the ENDO 2025 meeting of the Endocrine Society, reported an increase in C-peptide in T1D subjects who had undetectable levels of it at the start of the study. This is a good result, and motivated this phase-II study.  The results also indicated that the drug was effective in reducing inflammatory biomarkers like Th40, IFNγ, and TNFα.

The current trial introduces several changes based on the Phase 1 study. The most significant change is the route of administration, moving from an intravenous infusion to a subcutaneous injection. Intravenous infusions requires medical supervision (often by a nurse), while subcutaneous injection is the way insulin is injected (so anyone can do it).  

Phase 1 studies are more focused on testing safety, and while this one generated preliminary data on  efficacy, the current Phase 2 trial is designed to provide a more definitive answer on whether the drug works. This larger, longer, and placebo-controlled study will be critical to understanding the true potential of OPT101.

More Information

- ClinicalTrials.gov listing: https://clinicaltrials.gov/study/NCT06964087

- Previous Phase 1b study on ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05428943

- Sponsor Company: Op-T LLC

- NIH Grant Information: https://taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R01DK131196&arg_ProgOfficeCode=119

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Allogeneic CD7-Targeted CAR-T Cell (RD13-02) Starts Second Phase-I Clinical Trial

RD13-02 uses specially engineered immune cells designed to remove certain immune cells believed to drive the autoimmune attack that damages insulin-producing beta cells. Researchers hope that by removing these harmful immune cells, the immune system may stop attacking the pancreas and allow remaining beta cells to continue working.  This is a CAR-T therapy.  CAR-T is a genetic engineering technique which has been generating a lot of excitement recently.  A specific type of immune cell (called T cells) are taken from a healthy donor and then genetically engineered in the laboratory to attack a specific target.  They are then grown in large quantities and used for treatment.

RD13-02 targets a protein called CD7, which is found on the surface of most T cells and natural killer cells (both of these cells are parts of the immune system). In T1D, some T cells mistakenly attack insulin-producing beta cells in the pancreas.  The hope is that RD13-02 will attack these bad T-cells, and have a good impact on T1D.  Since these are foreign cells, RD13-02 also carries two engineered inhibitory receptors that help it evade rejection by the host's immune system, as well as other modifications designed to prevent the donor cells from attacking the patient's tissues.

RD13-02 was developed by Nanjing Bioheng Biotech Co., Ltd., a Chinese biotechnology company that operates internationally under the name Imviva Biotechnologies.  

This Study

There is a single treatment group of nine people, and no control group, so everyone enrolled receives the RD13-02 infusion. Participants must be between 18 and 40 years old and either be at-risk of T1D  (with two measured autoantibodies) or in their honeymoon phase.  RD13-02 is given as a single intravenous infusion.

The primary outcomes of the trial focus on safety and preservation of beta cell function via C-peptide levels during a mixed meal tolerance test. C-peptide levels are used to evaluate how well the pancreas continues to produce insulin.

Secondary outcomes examine several aspects of glucose control and disease progression. These include changes in insulin dose requirements, changes in HbA1c, fasting blood glucose levels, and time in range measured by continuous glucose monitoring. Another goal is to measure how long the infused RD13-02 cells persist and multiply inside the body after treatment.

Recruitment started in April 2026, with primary data collection expected to be complete by December 2027 and the study finishing by April 2028.

For those interested in participating or learning more, the study contact is:

Jingjing Jiang, MD, PhD  

Zhongshan Hospital, Fudan University, Shanghai, China  

Phone: 86-021-64041990  

Email: jiang.jingjing@zs-hospital.sh.cn

The trial is being conducted at a single site: Zhongshan Hospital, Fudan University, Shanghai, China.

Discussion

The key issues for all treatments aimed at removing the "bad" T-cells is how selective they are.  Do they remove the bad T-cells but leave the good ones.  Either extreme, getting rid of too many good T-cells or too few bad ones, will fail.  That is why treatments like this one need to be tested.

This is not the first human trial of RD13-02 in T1D. A separate, smaller pilot study (NCT07142161) run directly by Nanjing Bioheng Biotech enrolled three participants with autoimmune T1D.  That study has not yet finished, and results have not been published.  Also it was very strictly a safety study, with no data gathered on efficiency.  However, I assume it informed the design of the current, larger Shanghai trial.

RD13-02 has been tested in blood cancers including these studies:

• NCT06732492: A Phase 1 study of RD13-02 in patients with relapsed or refractory CD7-positive natural killer/T-cell malignancies, planned enrollment of 10 patients, currently recruiting.
• NCT06622694: A Phase 1 study in hematologic malignancies, 15 patients, currently recruiting.
• NCT05716113: Completed Phase 1 study in T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma, 20 patients, results presented at ASH 2024.  

More Information

• ClinicalTrials.gov listing (this study): https://clinicaltrials.gov/study/NCT07528105
• ClinicalTrials.gov listing (previous study): https://clinicaltrials.gov/study/NCT07142161
• Imviva Biotechnologies (Nanjing Bioheng Biotech international site): https://www.bioheng.com/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

SAB-142 From SAb Biotherapeutics Starts a Phase II Trial (SAFEGUARD)

Back in April, I blogged about a Phase-II study called "Anti-Thymocyte Globulin and Verapamil Start A Phase-2 Clinical Trial" (NCT06455319).  I should have included this trial at the same time, since they are closely related, but I didn't so I'm publishing this blog, now.

Both studies are testing ATG in honeymooners.  The previous study was testing either just ATG or ATG and Verapamil.  This study is testing a specific form of ATG produced by a specific company, SAb Biotherapeutics.  See the discussion section for details of how SAB-142 and ATG differ.  The first study is sponsored by a University, the second by a company, however I would not read too much into that, since the University was were many of the people involved in the company worked or continue to work.

About the SAFEGUARD Trial

SAFEGUARD (NCT07187531) is a randomized, double-blind, placebo-controlled Phase 2b study. It has two parts. Part A is an open-label, parallel-arm dose-ranging portion to confirm the dosing approach in adults; Part B, which is the main double-blind portion, will randomize participants to one of three groups — high-dose SAB-142, low-dose SAB-142, or placebo. The trial is enrolling approximately 159 participants total. All participants receive two treatment courses six months apart, and all are eligible for a 12-month long-term extension study after the main study ends.

To be eligible, participants must be between 5 and 40 years old (Part A is adults 15–40; Part B includes children from age 5), must weigh at least 16 kg, and must have been diagnosed with T1D within the prior 100 days according to American Diabetes Association criteria. They must have residual beta cell function (a random C-peptide of at least 0.2 nmol/L) and at least one T1D-related autoantibody (GAD65, IA-2, ZnT8, or insulin autoantibodies). People who have previously received teplizumab or any anti-CD3 treatment, or who have significant uncontrolled medical conditions, are excluded.

The primary endpoint for Part A is safety: specifically, the incidence of treatment-emergent adverse events, adverse events of special interest, and serious adverse events through four weeks after dosing. The primary endpoint for Part B is the change from baseline in C-peptide measured after a two-hour mixed meal tolerance test at 12 months — the same gold-standard measure of beta cell function used in all prior T1D immunotherapy trials. Secondary endpoints include continuous glucose monitoring measures (time in tight range, time in range, time above and below range), HbA1c levels, daily exogenous insulin use, hypoglycemia rates, and several composite measures of beta cell function and partial remission. SAB-142 drug levels and immunogenicity will also be tracked throughout.

SAB-142 is given by intravenous infusion — a drip into a vein, lasting roughly four to six hours, on two consecutive days. In the SAFEGUARD trial, participants receive two such treatment courses, six months apart.

The trial is supported in part through the Type 1 Diabetes Clinical Research Network (T1DCRN) and the Australasian Type 1 Diabetes Immunotherapy Collaborative (ATIC), both of which are supported by Breakthrough T1D (formerly JDRF). SAB BIO raised $175 million in a private placement in 2025 to fund the SAFEGUARD trial through completion.

To contact the SAFEGUARD study team:

    Phone: 1-844-763-1890

    Email: SAFEGUARD@sab.bio

Trial sites are located in:

United States: 

San Francisco, CA; Aurora, CO; Gainesville, FL; Miami, FL; Atlanta, GA; Indianapolis, IN; Boston, MA; Kansas City, MO; Buffalo, NY; Chapel Hill, NC; Fargo, ND; Philadelphia, PA; Fort Worth, TX; Houston, TX; Charlottesville, VA; Seattle, WA; Tacoma, WA

Elsewhere:

Australia: Brisbane, Nedlands (Perth), Parkville (Melbourne) ×2, St Leonards (Sydney), Westmead (Sydney), Austria: Graz ×2, Innsbruck, Vienna ×2, Belgium: Jette (Brussels), Leuven, Liège, Denmark: Herlev, Finland: Helsinki, Turku, France: Paris ×2, Germany: Augsburg, Hanover, Oberschleißheim (Munich), Italy: Milan, Turin, Verona, Lithuania: Kaunas, New Zealand: Auckland ×2, Christchurch, Dunedin, Hamilton, Wellington, Poland: Opole, Poznań, Warsaw ×3, Slovenia: Ljubljana, Spain: Barakaldo, Málaga, Seville, United Kingdom: Cambridge, Cardiff, Edinburgh, Liverpool, London ×2, Nottingham, Oxford

Discussion

What makes SAB-142 different from previous forms of ATG is how it is made. Most ATG currently used in medicine is derived from rabbits (called rabbit ATG or rATG): rabbits are immunized with human immune cells, and their resulting antibodies are collected and purified. SAB-142, by contrast, is produced using genetically engineered cattle — specifically cows that have been given a human artificial chromosome so that their immune systems generate fully human antibodies rather than rabbit antibodies. The drug is made by SAb Biotherapeutics, Inc. (also known as SAB BIO), a clinical-stage pharmaceutical company based in Miami.

There was a Phase-I clinical trial of SAB-142 done in 2025 in Australia.  I have not found a scientific journal article for these results, but SAb has published them at conferences.  It tested single ascending doses up to 4.5 mg/kg in healthy volunteers, and a 2.5 mg/kg dose in a small cohort of six adults with established T1D.  These showed that all four T1D participants who received SAB-142 at 2.5 mg/kg demonstrated preservation of C-peptide relative to baseline at Day 120, with three of the four showing C-peptide actually stayed at or above the baseline level. Those three participants also showed increases in average blood glucose time in range (from 73% to 85%) without any increase in injected insulin use. The placebo-treated participant with T1D showed the expected decline in C-peptide over the same period.  I consider these results to be good, but not great.  Certainly good enough to motivate a Phase-II trial, and that is where we are now.

Follow-up work from the same group, confirmed sustained immunomodulation and better metabolic control in a subset of participants. More recently, the MELD-ATG trial (NCT04509791), run by Universitaire Ziekenhuizen KU Leuven as part of the INNODIA network in Europe, enrolled 114 participants aged 5 to 25 to explore the minimum effective dose of rATG — that study completed in December 2024 and results are being analyzed.

There are several clinical trials (both past and present) testing ATG in various forms and in various ways:

• NCT01106157 was a 25 person, phase-I clinical trial of a combination or ATG and G-CSF.  Showed a small improvement in C-peptide
• NCT04291703 was a smaller, longer term follow on study to NCT01106157.   No strong results.
• NCT02215200 was a 89 person, phase-II, follow on to NCT01106157.  It found that GCSF did not improve results, but that ATG did improve C-peptide production. 
• NCT07216391 is an in-progress, 60 person clinical trial directly comparing ATG to Teplizumab in delaying the onset of T1D in people who are at risk (preventing people who already have two or more autoantibodies from progressing to T1D symptoms).
• The WAVE T1D trial (NCT07061574), is an in-progress, 120 person phase-II study at the City of Hope Medical Center.  I've blogged on it previously.  It is testing whether low-dose rATG followed by either adalimumab or verapamil preserves insulin secretion over two years in people aged 9 to 20 with new-onset T1D.  They hope to have results in 2030.
• The MELD-ATG trial (NCT04509791) completed enrollment of 114 participants in Europe in December 2024.  It found a small improvement in C-peptide results. 

Breakthrough T1D has provided support for the SAFEGUARD trial through its funding of the ATIC clinical trials network in Australia and the T1DCRN network. 

More Information

• ClinicalTrials.gov listing (NCT07187531): https://clinicaltrials.gov/study/NCT07187531
• Phase-I SAB-142 Results: https://ir.sab.bio/static-files/d6f0e78d-2429-4f5f-97e1-0b3b930f8c3c
• SAFEGUARD study website for participants: https://safeguardstudy.com/
• SAB BIO company website: https://www.sab.bio
• Press release: First patient dosed: https://ir.sab.bio/news-releases/news-release-details/first-patient-dosed-sab-bios-safeguard-clinical-trial-sab-142
• Press release: Phase 1 data:  https://www.globenewswire.com/news-release/2026/04/22/
• Breakthrough T1D Australia article on SAFEGUARD opening in Australia:  https://www.breakthrought1d.org.au/research/clinical-trials/
• T1D Fund (Breakthrough T1D venture arm) on SAB-142 IND clearance:  https://t1dfund.org/news/fda-provides-clearance-to-ind-application-for-type-1-diabetes-therapy-sab-142-by-sab-biotherapeutics/
• NCT04509791 publication: https://pubmed.ncbi.nlm.nih.gov/40976248/
• NCT04291703 publication: https://pmc.ncbi.nlm.nih.gov/articles/PMC8173803/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Rezpegaldesleukin (or NKTR-358) Starts A Phase-IIΔ Clinical Trial on Honeymooners (RESET T1D)

A new clinical trial is testing Rezpegaldesleukin, also known as NKTR-358, or REZPEG, as a potential treatment to slow or stop T1D in honeymooners.  Rezpegaldesleukin is a modified form of interleukin-2 (IL-2), which plays a key role in regulating the immune system. 

The drug is given by subcutaneous injection, similar to an insulin injection, once every two weeks. It has been studied across nine completed Phase 1 and Phase 2 trials in a total of approximately 746 participants for conditions including lupus, atopic dermatitis, psoriasis, and ulcerative colitis. It is not yet approved for any disease, anywhere in the world. 

Reminder: "Phase IIΔ" is my name for a trial that is the size of a phase II trial, but there has been no phase I trial of the treatment being tested, so in some ways it is like phase I (first in humans) but in other ways more like phase II (in size).

The Study

This is a randomized, double-blind, placebo-controlled Phase 2 trial enrolling 66 participants at three sites.  Participants are assigned in a 2:1 ratio — approximately 44 to Rezpegaldesleukin and 22 to a placebo.  Eligible participants must be between 8 and 45 years old, and diagnosed with T1D within the previous 100 days. Treatment consists of biweekly subcutaneous injections for 26 weeks, followed by a 6-month observation period, for a total follow-up of 12 months.

The primary goal of the study is to measure the change in C-peptide levels from the start of the study to the 1 year mark. C-peptide is used as a reliable indicator of how much insulin the body is naturally producing, which is essential for determining if the treatment is successfully protecting beta cells. Secondary goals include monitoring changes in A1c levels and the total amount of daily insulin required by participants. These endpoints provide a measure of whether the treatment is improving the long-term management of the disease and preserving the body's natural metabolic function.

Contact: Jessica Conaty — 813-396-9234 — Jessica.Conaty@epi.usf.edu

Locations:

• University of Pittsburgh, Pittsburgh, Pennsylvania (recruiting)
• Vanderbilt University, Nashville, Tennessee (not yet recruiting)
• University of British Columbia, Vancouver, British Columbia, Canada (not yet recruiting)

Primary completion is estimated for May 2028.

The trial is sponsored by the NIH and conducted by TrialNet. TrialNet is supported by  BreakthroughT1D (formerly known as JDRF). Nektar Therapeutics, the company developing Rezpegaldesleukin, is supplying the drug and providing support for pharmacokinetic analyses.

Discussion

The central idea behind Rezpegaldesleukin is that type 1 diabetes results in part from a failure of immune regulatory cells.  Researchers have known for many years that low doses of interleukin-2 can increase these cells and sometimes improve autoimmune diseases.  If you go to my blog and search for "IL-2" you will find a lot of previous clinical trials.  

In particular, a series of dose-finding trials carried out by researchers at Assistance Publique – Hôpitaux de Paris, including the DF-IL2 trial (NCT01353833) and the DFIL2-Child trial (NCT01862120), demonstrated that low-dose interleukin-2 could selectively expand regulatory T cells in both adults and children with T1D without triggering significant side effects, and this trial is built on that research. 

However, standard interleukin-2 has a short lifetime in the body and can also stimulate other immune cells that may worsen inflammation. Rezpegaldesleukin was engineered to overcome those problems by selectively activating regulatory T cells and remaining active longer after injection.

Rezpegaldesleukin is being developed by Nektar Therapeutics, a clinical-stage biotechnology company based in San Francisco. From 2017 until 2023, Nektar shared development rights with Eli Lilly and Company, which co-sponsored a large Phase 2 trial in lupus (the ISLAND trial, NCT04433585). That 291-patient trial was unsuccessful. Therefore, Eli Lilly chose not to continue development of the drug for lupus, and Nektar reacquired full rights to the program and continued the research in other diseases. 

More Information

• ClinicalTrials.gov listing: https://clinicaltrials.gov/study/NCT07142252
• Nektar Therapeutics company website: https://www.nektar.com
• Nektar Therapeutics pipeline page: https://www.nektar.com/our-pipeline/
• Wikipedia page for Rezpegaldesleukin: https://en.wikipedia.org/wiki/Rezpegaldesleukin
• Scientific paper describing earlier Rezpegaldesleukin trials: https://doi.org/10.1038/s41467-024-53384-1
• Earlier Trial: https://clinicaltrials.gov/study/NCT01353833
• Results: https://pubmed.ncbi.nlm.nih.gov/24622415/
• Another Earlier Trial: https://clinicaltrials.gov/study/NCT01862120
• Results: https://pubmed.ncbi.nlm.nih.gov/32607749/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Phase-I Clinical Trial of Islet Transplantation Into Eye

Pancreatic islet transplantation is an approach designed to restore the body’s ability to produce insulin by transplanting beta cells (insulin-producing cells) from a donor pancreas.  I don't consider most of these to be cures, because they require taking immune suppression drugs for the rest of the person's life.  For me, that is just trading one disease for another.

However, part of the eye (the anterior chamber) is what immunologists call an "immune-privileged" site — meaning the immune system is naturally less aggressive there than elsewhere in the body.  This trial is testing transplanting beta cells into the eye, rather than into the abdomen.  Instead of taking systemic anti-rejection drugs that affect the entire body, participants receive localized immune-suppressing treatment in the form of eye drops applied directly to the eye.  Because the immune suppression is localized rather than systematic (whole body), the risks are far less.  For me, that is a big advantage and means this might really be a cure.

The transplantation procedure is expected to take about twenty to thirty minutes. 

The Study

This is an old study that I have not previously blogged on.  It started in 2019, just before COVID and they hope to finish at the end of 2026 (but see below).

This is a small (2 person) Phase 1 trial where everyone gets the treatment.  There is no control group. To be eligible, participants must be between 18 and 75 years old and have T1D or type 2 diabetes (with or without insulin dependence). Most importantly, they must be legally blind in at least one eye — meaning the transplant goes into an eye that has already lost most or all useful vision, so the participant's sight is not put at additional risk.

The trial's three primary endpoints are all assessed at 24 months after transplantation. The first two focus on safety, but the third is effectiveness related: C-peptide in the fluid of the transplanted eye and direct visualization of the islet graft using standard eye examination tools and imaging. 

To learn more or inquire about participation, contact:

Midhat H. Abdulreda, Ph.D.

Diabetes Research Institute, University of Miami

Phone: 305-243-9871

Email: mabdulreda@miami.edu

Trial locations:

• Bascom Palmer Eye Institute, Miami, Florida, USA
• Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, USA

Discussion

The clinical trial registry claims they will finish collecting data from patients at the end of 2026 and publish results in 2027.  However, that is obviously not correct, because they are still recruiting, and need to follow patients for 2 years.  So obviously the clinical trial registry has not been updated.  I don't know if they have stopped recruiting and the completion dates are correct or if they are still recruiting and the completion dates are wrong.

No matter what is published, however, this study only includes 2 people, so even if the results are very positive, several more studies will be required.

Because the transplantation is in the eye, doctors can observe the transplanted cells directly using imaging tools that are already widely used in by eye doctors. In theory, this could allow researchers to monitor graft health and immune reactions in ways that are not possible when islets are transplanted elsewhere.

The scientific foundation for this trial was laid over many years in baboons. Animal studies were published in 2011, 2019, and 2020, by the same researchers involved in this trial.  These studies showed C-peptide creation, successful immune tolerance without whole body immune suppression, and general safety.

More Information

• ClinicalTrials.gov (US FDA registry): https://clinicaltrials.gov/study/NCT02846571
• Diabetes Research Institute — study page for participants: https://diabetesresearch.org/intraocular-islet-transplant/
• University of Miami Miller School of Medicine — announcement of the trial:  https://news.med.miami.edu/miller-school-diabetes-trial-eye-pancreatic-islet-transplant
• CellR4 publication on intraocular islet transplantation: http://www.cellr4.org/article/2120

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Anti-Thymocyte Globulin and Verapamil Start A Phase-2 Clinical Trial

Researchers at the University of Florida are launching a new Phase 2 clinical trial to evaluate a combination therapy for individuals recently diagnosed with type 1 diabetes. This study, titled "Precision Administration of Anti-Thymocyte Globulin (ATG) With or Without Verapamil," aims to preserve the body's ability to produce its own insulin by combining two different types of medication. The first is anti-thymocyte globulin, which is a protein-based drug designed to modify the immune system by targeting T cells. The second is verapamil, a pill commonly used to treat high blood pressure. By using these two treatments together, investigators hope to stop the immune system's attack on the pancreas while simultaneously reducing the stress on the remaining insulin-producing cells.

As I’ve discussed in past blog posts, both treatments have shown early promise, but not success.  Here are two on ATG:

https://cureresearch4type1diabetes.blogspot.com/2023/05/low-dose-atg-preserves-beta-cell.html

https://cureresearch4type1diabetes.blogspot.com/2018/05/results-from-phase-ii-atg-and-gcsf.html

and here is one on Verapamil:

https://cureresearch4type1diabetes.blogspot.com/2022/11/verapamil-preserves-beta-cell-function.html

.

The Study

This is a phase 2 randomized controlled trial involving 60 participants aged 6 to 35 who have been diagnosed with type 1 diabetes within the last 100 days. Participants will be randomly assigned to receive either ATG or a placebo infusion. After one year, they will be re-randomized to receive either Verapamil or no additional treatment for a second year.

The primary goals of the study are to measure the difference in C-peptide levels (a marker of insulin production) between the ATG and placebo groups at 12 months, and to compare how these levels change over the first 6 months. Secondary goals include exploring the mechanisms behind how these treatments might work together to preserve beta cell function.

This research is supported by BreakthroughT1D (formerly known as JDRF).

For those interested in more information or participation, the global contact for the trial is:

Jennifer L. Hosford, MPH Phone: 352-294-5760 Email: jennifer.hosford@peds.ufl.edu

The trial is currently recruiting participants at the following locations in the US:

• University of Florida, Gainesville, Florida
• Barbara Davis Center for Diabetes, Aurora, Colorado
• University of Miami, Miami, Florida (Collaborating Institution)

Discussion

Previous research in Anti-Thymocyte Globulin research has already shown a small effect to preserve C-peptide for a year or two. This is why the addition of Verapamil is interesting. In a mice study, the combination led to a reversal of T1D.   Both of these treatments have a solid safety record for people.

Verapamil has also shown promise in preserving beta cell function. A 2018 study by Ovalle and colleagues at the University of Alabama found that verapamil helped maintain C-peptide levels in adults with recently diagnosed type 1 diabetes.

More Information

The FDA Clinical Trials Registry: https://clinicaltrials.gov/study/NCT06455319

Cancelled Study: https://clinicaltrials.gov/study/NCT07061574

The University of Florida Diabetes Institute: https://diabetes.ufl.edu/

Wikipedia page for Anti-thymocyte globulin: https://en.wikipedia.org/wiki/Anti-thymocyte_globulin

Wikipedia page for Verapamil: https://en.wikipedia.org/wiki/Verapamil

DiaTribe article on Verapamil: https://diatribe.org/diabetes-medications/verapamil-and-type-1-diabetes

The 2018 Haller study in Diabetes Care: https://pubmed.ncbi.nlm.nih.gov/30012675/

The 2025 Degroote study in Diabetologia: https://doi.org/10.1007/s00125-025-06490-8

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

GentiBio starts a Phase-I Clinical Trial on GNTI-122 in Honeymooners (POLARIS)

GentiBio, Inc. is sponsoring a clinical trial known as POLARIS, which aims to evaluate a cell therapy called GNTI-122 in honeymoon adults.  It is created specifically for each participant using their own blood cells.  GNTI-122 is administered as a single dose. 

GNTI-122 is designed to modify regulatory T cells - immune cells that help prevent the body from attacking its own tissues. By enhancing the function of these cells, the treatment may help protect the remaining beta cells.  

The Study

The POLARIS study (NCT06919354) is a 78-week, single-arm, multi-center, Phase 1 trial.  Everyone gets the treatment; there is no control group and no blinding.  The study is organized into three cohorts. The first two, each with three participants, will receive GNTI-122 alone at a low dose (Cohort 1) and a high dose (Cohort 2), respectively. The third cohort, consisting of 10 participants, will receive a high dose of GNTI-122 in combination with rapamycin. 

This study is open to adults between 18 and 45 years old who have been recently diagnosed with T1D (within 120 days of screening). They must test positive for at least one T1D-associated autoantibody, be on insulin therapy, and carry a specific genetic marker called HLA-DRB1*04:01. This treatment uses an IV line to collect blood cells from the person being treated, for the therapy's manufacture.

This trial will primarily be looking at safety issues and measuring how the engineered cells behave in the body, but they will also measure C-peptide, which indicates the body's natural insulin production.

Individuals interested in learning more about the POLARIS clinical trial can contact Kristin M Neff at GentiBio, Inc. The phone number provided is 857-327-5483, and the email address is clinical_ops@GentiBio.com.

The POLARIS study is being conducted at nine locations across the United States:

• Duarte, California: City of Hope Medical Center
• San Diego, California: University of California – San Diego
• San Francisco, California: University of California – San Francisco
• Gainesville, Florida: University of Florida – Gainesville
• Miami, Florida: University of Miami, Diabetes Research Institute
• Boston, Massachusetts: Joslin Diabetes Center
• New York, New York: Icahn School of Medicine at Mount Sinai
• Chapel Hill, North Carolina: University of North Carolina at Chapel Hill (currently recruiting)
• Durham, North Carolina: Duke University (currently recruiting)

Discussion

One unusual aspect of the POLARIS study is its use of rapamycin in combination with GNTI-122. Rapamycin is an immunosuppressant drug that has been used for decades to prevent organ transplant rejection. In this study, it is being tested to see if it can help the modified cells survive longer in the body.

More Information

• ClinicalTrials.gov Registry: https://clinicaltrials.gov/study/NCT06919354
• GentiBio, Inc. (Sponsor): https://gentibio.com/
• GentiBio POLARIS Study Page: https://www.gentibio.com/polaris-study

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Results From An Omega-3 and Vitamin D Clinical Trial In People With Long Standing T1D

Researchers at the University of Miami are exploring whether a combination of two well-known supplements—omega-3 fatty acids and vitamin D—might help preserve insulin production in people with type 1 diabetes. The study, called POSEIDON, is testing whether high doses of these supplements, taken together, can slow the progression of the disease by protecting the remaining beta cells in the pancreas.  These substances are classified as nutritional supplements rather than traditional pharmaceutical drugs.  In the USA this means that there is no approval process required to show they are safe or effective.

The results for this trial were uploaded to the US FDA's clinical trial registration web site.  However, I cannot find them published in a journal.  Since the trial was unsuccessful, they might not have been published.  An "after the trial" analysis was published, which I discuss below.  

Results

The primary outcome results focused on the change in C-peptide levels, after eating a meal, over one year.  C-peptide levels declined in both groups over the course of the year, which is the typical progression of the disease.  C-peptide levels dropped about the same amount in treated people as in untreated people (there was no statistically significant difference), so the trial was unsuccessful.  

This trial was randomized, open-label format, meaning both the researchers and the participants knew which treatment they were receiving. The study enrolled 27 participants who were divided into groups based on their age and how long they had lived with the disease. This included both children (ages 6 to 17) and adults (ages 18 to 65), as well as individuals with a new diagnosis (within six months) and those with established T1D (up to 10 years).

Discussion

Post-Hoc  (After The Study) Analysis

The phrase "post-hoc" refers to studies that use the data collected from one study, but are designed knowing what that data is.  They are not blinded, but quite the opposite, publish results that only come apparent with analysis done knowing the data.  

These studies are generally not used for drug or device approvals, because it is easy to design a study that shows good things, by carefully crafting it to avoid the bad things that the researcher knows are in the data.  However, they can show interesting directions for future work, or results that were not even under consideration when the study was originally designed.

These researchers published a post-hoc analysis which suggested that at the time of diagnosis, people with lower Vitamin D levels also had lower fasting C-peptide levels, but no difference in post meal C-peptide levels.  I found these results uninteresting for a couple of reasons.  The biggest is that there have been much larger studies looking at Vitamin D and T1D diagnosis.  The second is that in other studies that I've seen have fasting and post-meal C-peptides tightly related (going up and down for the same reasons).  So I think seeing an effect in one, but not the other is likely a random effect. 

Words vs. Reality

This is how AI chatbots describe the two treatments tested here:

Omega-3 fatty acids, found in fish oil, have been studied for their potential to reduce inflammation and support heart health. Vitamin D, plays a role in immune function and may help regulate autoimmune responses. When taken together, these supplements might offer a dual benefit for people with T1D by reducing inflammation and supporting beta cell survival.

That sounds positive, but shouldn't.  Notice the use of weasel words: "studied for their potential", "support", "help regulate", "might offer", and "might benefit".  In fact, neither Omega-3 nor Vitamin D has been found to help inflammation or immune function in clinical trials such that they could be approved for use in the US.  It is important to remember that these words are widely used in blogs, news reports, and sales literature to trick people into thinking these treatments help in some way.  (Their widespread use on the web causes them to seep into AI chat bot results.)  The unsuccessful results from this clinical trial, and several other clinical trials, show that they do not work, or at the very least, we do not have evidence that they work, and their promoters are speculating on future results which may never come.

I want to stress that this is not a simple minded failure of AI.  It is a simple minded failure of the world wide web.  AI is accurately repeating the mistake made by the web and people on the web, which is to treat opinions (and especially opinions designed to attract viewers) on an equal footing to data from scientific studies.  To put it bluntly: 1000 bloggers saying Vitamin D is a wonder cure is less substantive than one well done study showing it is not.  In a sense, general AI is implementing the thought process of a random person who can hear volumes and count sources, but can not evaluate anything.

More Information

FDA Clinical Trials Registry: https://clinicaltrials.gov/study/NCT03406897

Trial Description: https://diabetesresearch.org/poseidon/

Trial Details: https://www.cellr4.org/wp-content/uploads/sites/2/2018/04/2018-03-POSEIDON-Protocol-Consent-Assent-2.pdf

The research publication related to the study's rationale: https://pubmed.ncbi.nlm.nih.gov/27467009

Post-Hoc Analysis: https://academic.oup.com/jes/article/9/6/bvaf061/8110156

VITAL Results: https://www.vitalstudy.org/findings.html

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Open Letter: Focus On Hidden Transplanted Beta Cells

An open letter to everyone who cares about research aimed at type 1 diabetes cures.

I've been blogging on research aimed at curing type 1 diabetes for almost 20 years, but I've never sent out a message like this before.  However, for me, the results from a single person clinical trial of Sana Biotechnology's UP421 treatment should motivate a change in how we all think about research to cure T1D.

Until now, I've taken a "diversification of research" point of view.  At any time, there are 20 or 30 

active research projects aimed at curing T1D, and I supported all of them, based on their results to date.  I did not favor one over another based on what I thought would happen in the future.  My policy was that we don't know which one will succeed, so we need to support all of them and see which one actually does succeed.

But now, I'm starting to change my point of view.  I'm starting to see that one approach is working better; is moving to the front of the competitive pack, and deserves more support and more optimism, than the others.

Sana's UP421 study gave one person a small dose of genetically engineered beta cells.  The genetic engineering (using the CRISPR-Cas9 gene editing technology) is designed to render the cells invisible to the immune system in order to avoid the need for any immune suppression, both to prevent foreign organ rejection and to prevent autoimmune attacks.  C-peptides were generated and immune suppression was not needed.  Six month results were published in the New England Journal of Medicine, and they have released one year results at an investor's conference.  Sana is planning on a follow up product, SC451 to start clinical trials in 2026.

Obviously, this result has important limitations: one person, less than one year, a small dose, and a small effect.  It used cadaver beta cells and Sana is switching to a different cell source for the future.  However, what it did show was invisibility to the immune system, and steady generation of insulin for the first 6 months of data.  It did generate less insulin for the next six months, dropping to about half of its initial high point, and that will need to be investigated.

The reason I am excited about this result is that the required scientific breakthrough(s) have already happened.  The genetic engineering required to hide the transplanted beta cells appears to be successful in this one person study.  Much of the study's results were aimed at confirming this invisibility.  The remaining work is much more engineering development than scientific breakthrough.  Sana needs to 

transplant more cells, they need to be tested for longer, and (especially) in more, different people. 

I think that all organizations working to cure type 1 diabetes, should do the following for the next few years, and I think that we, as a community that cares about T1D research should be encouraging them to:

1. Establish a focus on genetically engineering beta cells which evade the immune system, as a potential cure for type 1 diabetes.
2. Put 5% of their research funds into helping Sana's SC451 product (or successors) progress down the path towards general availability.
3. Start advocating with the FDA now to smooth the approval process for this treatment when it is available, and to ensure insurance coverage for this treatment.
4. Put an additional 5% (or a little more) into adjacent research, non-Sana projects to use genetic engineering to hide beta cells.

Research is about the unknown, and I'm not saying that Sana is going to cure T1D, but I think they are close enough so that we should focus more on them and their research area (generically engineering beta cells to avoid the immune system).  I don't think spending 10% of our research money on this one area is extreme right now. 

BreakthroughT1D's Project ACT (Accelerate Cell Therapies), which they started in 2024, is already a step in this direction.  It's focus is wider than beta cells genetically engineered to hide from the immune system, but it certainly covers them.  In addition, the T1D Fund (BreakthroughT1D's venture capital business fund) is already funding Sana .  There is also a Swedish foundation which is focused on funding this research in a university setting.  These are all great steps, but the entire T1D community needs to "put a brick on the accelerator" for this.  

My thinking here is similar to BreakthroughT1D's (then JDRF's) policy on the Artificial Pancreas.  I believe that JDRF's actions there sped up availability of an Artificial Pancreas by several years, and I think we can do the same now, but this time with a cure.  

I have often said that the first signal we will get that a cure for type 1 diabetes will occur

is that one person will be cured in a clinical trial.  Sana's 2025 result is not quite that, but it is on the path.  

None of this means that I'm going to stop following (or even slow down following) other research areas.  I continue to believe that limiting ourselves to one one path to a cure is a dangerous form of scientific extremism.  So while I am calling on more focus and more support for genetic engineering to hide transplanted beta cells from the body's immune system, I'm not going to exclude other research paths from my blog.  I will continue to report on all cure focused research.

Note: There is also another company called Sana which does AI work.  This research is being done by Sana Biotechnology.

More Information on Sana Biotechnology's results:

News Coverage: https://www.medscape.com/viewarticle/transplanted-islet-cells-survive-without-immune-suppression-2025a1000kqt

My Blogging: https://cureresearch4type1diabetes.blogspot.com/2025/04/sana-biotechnology-reports-first.html

Publication: https://www.nejm.org/doi/abs/10.1056/NEJMoa2503822

Clinical Trial: https://www.clinicaltrials.gov/study/NCT06239636

Press Release: https://ir.sana.com/news-releases/news-release-details/sana-biotechnology-announces-publication-new-england-journal

Foundation created to support the university side of this research:

https://www.uu.se/en/news/2025/2025-11-14-new-foundation-shortens-pathway-to-a-cure-for-type-1-diabetes

About Project ACT:

https://www.breakthrought1d.org/project-act/

https://www.thejdca.org/publications/report-library/archived-reports/2025-reports/breakthrough-t1ds-project-act-a-dedicated-cure-initiative.html

https://www.thejdca.org/publications/report-library/archived-reports/2025-reports/an-update-on-project-act.html

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions.  I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs.  I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately.  My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here.  I am obese and right on the border of T2D and therefore may be taking drugs for those conditions.  My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog! 

SAR442970/Brivekimig Starts a Phase IIΔ Trial In Honeymooners (T1D OBTAIN)

The treatment being tested is called Brivekimig (previously SAR442970). It is a type of biologic drug known as a bispecific nanobody. It is a small, engineered protein designed to bind to and block two specific molecules in the immune system simultaneously: Tumor Necrosis Factor-alpha (TNF-alpha) and OX40 Ligand (OX40L). 

TNF-alpha and OX40L are two of the chemical messengers that help coordinate and sustain the autoimmune attack which starts off T1D. By blocking both of these messengers at the same time, the drug aims to interfere with the autoimmune process, potentially protecting the remaining beta cells from further destruction and preserving the body's ability to produce some of its own insulin.  TNF-α is a well-known driver of inflammation, while OX40L plays a role in activating immune cells that attack beta cells. By targeting both, researchers hope to protect beta cells from destruction while avoiding the broad immune suppression seen with some other treatments.

SAR442970 is given as a subcutaneous injection, similar to how insulin is administered.

Reminder: Phase IIΔ is my name for a trial that is the size of a phase II trial, but there has been no phase I trial of the treatment being tested, so in some ways it is like phase I (first in humans) but in other wase like phase II (in size).

The Trial

This is a randomized, double-blind, placebo-controlled trial, meaning participants are randomly assigned to receive either SAR442970 or a placebo, and neither they nor the researchers know who is getting which treatment. The study includes 84 participants aged 12 to 35 who were diagnosed with T1D within the last 90 days.

The trial is divided into two parts: Part A includes adults (18–35 years old), and Part B includes adolescents (12–21 years old). Participants will be treated for 52 weeks, followed by a 26-week follow-up. The primary goal is to measure changes in C-peptide levels at 26 weeks. Secondary outcomes include changes in insulin requirements, A1c levels, and other measures of diabetes management.

Participants will be randomly assigned, in a 3-to-1 ratio, to receive either SAR442970 or a placebo. This means for every four people who join, three will receive the active drug and one will receive the placebo. 

The primary goal, or primary endpoint, of the study is to measure the change in C-peptide levels after 26 weeks of treatment. C-peptide is released along with insulin and serves as a reliable marker of how much insulin a person's body is still making. Preserving C-peptide is the main objective of therapies like this one. Secondary endpoints include looking at C-peptide levels after a full year, as well as changes in A1c, daily insulin requirements, and time spent in the target glucose range. The study will also carefully monitor the safety and tolerability of the drug over the entire treatment and follow-up period.

For more information about participating in this trial, you may contact Sanofi by phone at 800-633-1610 (extension 6) or by email at contact-us@sanofi.com.

The trial is being conducted at multiple locations across several countries, including the US, Argentina, Australia, Brazil, Canada, Chile, Israel, and Saudi Arabia.

Discussion

A noteworthy aspect of the T1D OBTAIN trial is its use of a bispecific nanobody. Unlike traditional antibodies, nanobodies are smaller and can be engineered to hit multiple targets at once. This dual-target strategy, aiming at both TNF-alpha and OX40L, represents a more complex approach than simply blocking a single immune pathway, which has been the focus of most past research in this area.

This treatment was developed by Sansofi, and they are running several different clinical trials to test it on different diseases: Crohn’s disease (Colitis ulcerative), Hidradenitis Suppurativa, Focal Segmental Glomerulosclerosis, and Minimal Change Disease.  I'm not sure why they chose those diseases.  The first is an autoimmune disease, similar in some ways to T1D, the second is an immune disease (but not autoimmune), while the causes of the third and fourth are not really known, and might be a lot of things.

The summary of the running trials is this: The Hidradenitis Suppurativa phase-II trial ended successfully, and they started a larger phase-II trial.  The other trials are still ongoing.  These are all roughly 90 person, phase-II trials and are expected to end in the next year or two.  Because Hidradenitis Suppurativa is an immune disease, but not an autoimmune disease (like T1D), I don't think we should read much into the good results seen in that study. 

More Information

• ClinicalTrials.gov Listing: https://clinicaltrials.gov/study/NCT06812988
• World Health Organization ICTRP Listing: U1111-1307-7268
• Sanofi Plain Language Summary Page for this Study: https://sanofi.trialsummaries.com/Study/StudyDetails?id=26518&tenant=MT_SNY_9011
• EU Summary of Trials: https://clinicaltrials.eu/drug/sar442970/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Rituximab and Treg Cells Starts a Phase IIΔ Trial In Youth At Risk Of Diabetes

A new clinical trial is exploring whether two different immune therapies, used alone or in combination, can delay or prevent the onset of  T1D in people who are at high risk, but have not yet been diagnosed with T1D. The study will test a cell-based therapy using a patient's own cells (regulatory T cells) and and a drug called rituximab.

It involves drawing a person’s blood, isolating a specific type of immune cell, multiplying these cells in a laboratory, and then infusing them back into the same person. These regulatory T cells are the body’s natural “peacekeepers,” responsible for preventing the immune system from attacking its own tissues.  Rituximab is a well-established prescription medication that works by targeting and removing a different type of immune cell, known as a B cell. B cells play a role in the autoimmune attack that causes T1D.

The regulatory T cells will be administered through an infusion, while rituximab will be given as an injection. The trial will involve multiple infusions and injections over a period of time. This is not a new treatment; both regulatory T cells and rituximab have been used in other diseases. However, combining them to prevent type 1 diabetes is novel.

Rituximab has been approved by the FDA for many years to treat other autoimmune conditions, such as rheumatoid arthritis, as well as certain types of cancer.  Its safety profile is well understood from its use in these other conditions. Treg therapy is still experimental and not approved for general use. However, it has been studied in human clinical trials for more than a decade for T1D and other autoimmune diseases. To date, these studies have generally shown it to be safe.

The Study

This study is a randomized, controlled trial, participants will be randomly assigned to different treatment groups. The trial will include approximately 150 children aged 6 to 16 who already have two autoantibodies associated with type 1 diabetes and therefore are at very high risk of developing type 1 diabetes. They will be followed for five years.

There will be four groups in the trial, which cover all the combinations of treatment and  placebo:

1. Group I will receive both regulatory T cells and Rituximab.

2. Group II will receive regulatory T cells and a placebo.

3. Group III will receive Rituximab and a placebo.

4. Group IV will receive two placebos, one simulating Rituximab, the other the cell infusion.

The primary endpoints of the study are the number of days from the start of the treatment to the first signs of high blood sugar levels and the number of adverse events reported. 

The secondary endpoints include C-peptide levels, daily insulin dose, and the number of participants in remission. 

Families interested in the trial can contact the study team for more information:

Marta Druch, Clinical Trial Director  Email: m.druch@poltreg.com  Phone: +48 731 471 845

Grzegorz Orlik, Medical Director  Email: g.orlik@poltreg.com  Phone: +48 790 680 020

The trial is being conducted at eight locations across Poland:

• Bialystok, Poland (Recruiting)
• Gdansk, Poland (Not yet recruiting)
• Katowice, Poland (Not yet recruiting)
• Lodz, Poland (Not yet recruiting)
• Lublin, Poland (Not yet recruiting)
• Opole, Poland (Not yet recruiting)
• Rzeszów, Poland (Not yet recruiting)
• Wroclaw, Poland (Not yet recruiting)

More details, including full eligibility criteria, are available on the clinical trial registry: https://clinicaltrials.gov/study/NCT06688331  

https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505226-33-00

This trial is funded by PolTREG S.A., a company specializing in cellular therapies.

Discussion

One thing that I like about this study is that they are testing two different treatments, but all the possibilities (both treatments, one treatment, the other treatment, and no treatments).  This means it should be easy to see if either treatment is helpful and if the treatments help each other be more effective than either alone.  

Running a clinical trial on children ages 6 to 16 is also good, since that is the age that most people with T1D are diagnosed. 

The long duration of the trial, five years, means we will be waiting a long time for results.  This is unfortunate, but if the goal is prevention, I do not see any other way to run the clinical trial. 

Related Trials

Study NCT00279305, a Phase 2 study which completed in 2009 with 87 honeymooner T1D participants aged 8-45, investigated Rituximab. The study found that rituximab preserved C-peptide generation as compared to placebo.

Study NCT01280682, completed in 2018 in China.  It enrolled 120 honeymooner T1D patients aged 8-70.  This trial showed that rituximab treatment slowed the decline in C-peptide compared to insulin-only treatment and resulted in lower HbA1c levels at six months.

Study NCT03929601 is an ongoing Phase 2 study with 74 honeymooner T1D participants aged 8-45. This study compares sequential Rituximab and Abatacept therapy to Rituximab alone, aiming to improve C-peptide response at 24 months. Secondary endpoints include safety, insulin use, and HbA1c. It is expected to finish in March 2029.

Previous blogging: https://cureresearch4type1diabetes.blogspot.com/2024/08/combo-of-rituximab-and-abatacept-starts.html

Study NCT07041268, an ongoing Phase 2 trial recruiting an estimated 116 honeymooner T1D adolescents (12-17 years old) in Russia, is examining repeated Rituximab. The primary endpoint is the change in mean C-peptide levels, with secondary goals including insulin dose and HbA1c. This study anticipates completion by March 2028.

More Information

For more information about this clinical trial, you can visit the following links:

• FDA's Clinical Trials Registry: https://clinicaltrials.gov/study/NCT06688331
• EU Clinical Trials Registry: https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505226-33-00
• Company Website: https://www.poltreg.com
• Press Release Announcing the Start of This Clinical Trial: https://poltreg.com/poltreg-doses-first-patient-in-phase-ii-trial-for-pre-symptomatic-type-1-diabetes-with-ptg-007/
• Web Page Created by the Researchers to Explain the Study to Participants: https://www.poltreg.com/study-explanation
• Wikipedia Page for Rituximab: https://en.wikipedia.org/wiki/Rituximab
• DiaTribe Article on This Treatment: https://diatribe.org/rituximab-and-regulatory-t-cells-for-type-1-diabetes
• JDCA Article on This Treatment: https://www.jdca.org/rituximab-and-regulatory-t-cells-for-type-1-diabetes

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions.  I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs.  I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately.  My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here.  I am obese and right on the border of T2D and therefore may be taking drugs for those conditions.  My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!