Dompé Starts GLADIATOR, a Phase-III Clinical Trial of Ladarixin

Ladarixin is a drug being develop by Dompé (an Italian company).  It inhibits activity on parts of the immune system called the IL-8 receptor (which has two subtypes: IL-8a and IL-8b).  Dompé hopes that this will stop the progression of type-1 diabetes. 

Before I discuss the phase-III study, I want to say something very important: A previous phase-II study, done by the same company (Dompé) of the same drug (Ladarixin) was successful when measured at 6 months, but unsuccessful when measured at 12 months (and 12 months was the primary end point).  I discuss previous results below.  However, the previous study gave people about 3 months of treatment, but the new study gives them about 12 months, a much longer treatment protocol.

The Phase-III Study

This is a big study.  Phase-III studies for T1D are usually about 300 people, and this one is 327.  Also, 2/3s of the people in the study will get the treatment; only 1/3 are controls who get the placebo.  It started near the end of 2020, and they plan to finish in mid 2025.

This study will enroll honeymooners (within 180 days of diagnosis).  About 200 will be children (aged between 14 and 17), and about 127 will be adults (between 18 and 45).

Ladarixin is a pill which people will take twice a day for two weeks, and then not take for two more weeks, and then they will repeat this cycle for a year.  They will then be followed for an additional year.  The primary results are C-peptide and A1c measurements after the year of treatment, and secondary results include these same measures throughout the 2 year trial and several more interesting outcomes.  These include time in range, low blood glucose episodes, and patients not requiring injected insulin (!).

An interesting design point of this study is that it is fully blinded for the first 18 months.  This will cover the primary end point, and 6 months after that for all of the people enrolled, since it is measured from the last person enrolled, not the first.  After that the blinding is lifted.  I assume this will lead to faster publication (especially of the primary end points), since they will not need to wait the full 24 months to start the data analysis.

First person given Ladarixin: https://www.dompe.com/en/media/press-releases/domp%C3%A9-announces-first-patient-enrolled-in-phase-3-trial-of-ladarixin-an-oral-investigational-cxcr1-2-inhibitor-in-new-onset-type-1-diabetes-t1d
US Clinical Trial: https://www.clinicaltrials.gov/ct2/show/NCT04628481
Europe Clinical Trial: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001926-71/DE

Recruiting Locations

This study is recruiting from 58 different locations, all over the world and the United States.  It is a large endeavor.  I can not list them all here, but they are listed on the clinical trial record: https://www.clinicaltrials.gov/ct2/show/NCT04628481

If you are in Northern California, contact info is: Center of Excellence in Diabetes & Endocrinology (CEDE) , Sacramento, California, United States, 95821-2123, Contact: Gnanagurudasan Prakasam, MD       prakasg@sutterhealth.org 

United States locations include:  Arizona, California, Colorado, Delaware, Florida, Georgia, Illinois, Indiana, Kansas, Kentucky, Massachusetts, New York, North Carolina, Pennsylvania, Texas, and Virginia.

International locations include: Belgium, Georgia, Germany, Israel,  Italy, Serbia, and Slovenia (many sites in most countries).

Results From A Phase-II Study

The results of this study were published as a paper, here:
https://pubmed.ncbi.nlm.nih.gov/35589610/
and here are the key results:

Copyright 2022.
Provided for educational purposes only.

You can see that the people who got the drug (blue line) did better than the people who did not (brown or orange line).  However, the P value is too high to be statistically significant (.12 versus .05 or lower).  But also notice that even for the treated group, the value was never higher than it started.  To me, that suggests that this drug might have stopped beta cell destruction for a few months, but never led to beta cell regeneration.  This result has been seen in the past for other drugs, but - so far - has not led to effective treatments. 

Press Release: https://www.biospace.com/article/releases/dompe-presents-phase-ii-clinical-trial-results-for-ladarixin-in-new-onset-type-1-diabetes-at-the-american-diabetes-association-s-scientific-sessions/

Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT02814838

The results of this study were published as a poster in the ADA 2020 conference: https://diabetesjournals.org/diabetes/article/69/Supplement_1/249-OR/56830/249-OR-A-Randomized-Double-Blind-Phase-2-Trial-of

Discussion

The big discussion point here is: why is Dompé running a phase-III study when their previous phase-II study was unsuccessful at the primary end point?  There are three answers to that question and they are all important in their own way:

First, although the results were unsuccessful at 12 months, the same measurements were successful at 6 months.  An optimist would say that the treatment worked, just not in the time frame that had previously been selected as the primary outcome.  By giving the treatment for a longer period of time (12 months instead of 3), the researchers hope to have a successful outcome.  In real life, the important time frame is not 6 months or 12 months, but a lifetime, so quibbling over exactly when a treatment is measured may not be productive.

Second, Dompé may know something that no one else knows, or they may be focusing on some specific results which they think is important to improving future results.  Remember, they have been developing this drug for years.  They also may have data from the earlier study which was not published, but which gives them hope not obvious to the rest of us.  In fact, their ADA poster reporting on their previous results included this quote:

Although primary endpoint was not met, secondary and subgroup analyses suggest further investigation of LDX [Ladarixin] in new onset T1D may be warranted.

This quote certainly covers the 6 month results (which were a secondary result), but could be referring to other results which give Dompé more hope of success in the future.

Third,  there is no requirement (legal, scientific, medical, or any other) that previous clinical trials must be successful in order to run more clinical trials on the same drug.  As I'm fond of saying, in order to run the first clinical trial for a new drug, you need three things: a researcher who wants to run it, money to run it, and (in the US) a new drug approval from the FDA.  However, the new drug approval only needs to show safety, not success of any kind.  For a second clinical trial, you already have the new drug approval, so all you really need is a researcher and money.

In the past, this has lead to both good and bad results.  In the case of Teplizumab, an early company chose bad end points, and had an unsuccessful clinical trial because of it.  However, the researchers were able, years later, to get another company involved with different end points and have a successful trial.  This led eventually to FDA approval.  On the other hand, in the case of BCG, Faustman's lab ran unsuccessful trial after unsuccessful trial, using them as fundraising opportunities, but not (in my opinion) progress towards cure success.

My personal view is that Dompé's result is more like Teplizumab than like BCG.  Also, giving the drug for longer seems like a direct way to convert the previous unsuccessful result to successful.  So I'm optimistic about the overall chance of being successful in the primary outcome in the future.  I'm much more curious as to the size of the result.  It appeared that the untreated group's insulin production dropped (as expected during the honeymoon), but the treated group's insulin production stayed flat.  Results similar to this have been seen before, but it remains a challenge to convert these types of results into a cure or a delay.  Hopefully, this drug will do better.

Another interesting point about this study is that there is a secondary end point, which is (to me) incredibly aggressive.   If this end point shows any response, it would be great news.  It is "Percentage of patients not requiring insulin therapy", which - in a certain sense - is a measure of a practical cure.  They are hoping that some people will not need to inject insulin at all.

More To Read

Baylor participation: https://www.bcm.edu/healthcare/clinical-trials/h-49339

Phase-II Poster: https://diabetes.diabetesjournals.org/content/69/Supplement_1/249-OR

Phase-II Press Release: https://www.prnewswire.com/news-releases/dompe-presents-phase-ii-clinical-trial-results-for-ladarixin-in-new-onset-type-1-diabetes-at-the-american-diabetes-associations-scientific-sessions-301076774.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 JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates 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.

T1D Research News (Quick Bits from April)

This blog covers three pieces of news which do not apply directly to cure focused research, but which I found interesting anyway.

• Tight Honeymoon Control Does Not Improve Long Term Insulin Production
• Insulin Price Drops
• Sanofi Buys Provention
  

Tight Honeymoon Control Does Not Improve Long Term Insulin Production

For many decades, there has been a theory that sugar itself was toxic to beta cells, and that tight blood glucose control during the honeymoon phase would result in longer beta cell survival, more natural insulin production, and therefore better long term results.  I don't think this was ever the majority belief, but some people definitely did believe it, and they advocated for very tight controls in recently diagnosed people.

The study reported on below compared C-peptide production in people who used a hybrid closed loop at diagnosis to those who did not.  Those with the hybrid closed loop were in range 14% more than those who did not, showing better control.  However, this did not affect C-peptide production.

https://jamanetwork.com/journals/jama/fullarticle/2801975

Insulin Price Drops

The retail cost of insulin has been going up for decades, even as the manufacturing cost has been dropping (relative to inflation).  However, that is ending as Sanofi, Eli Lilly, and Novo Nordisk have all announced huge price cuts in the United States.   See https://www.cnn.com/2023/03/16/health/sanofi-insulin-price-reduction/index.html (and many other news sites) for details. 

Why Is This Happening?  

This is happening now because these companies are about to face a new competitor, who they have never faced before.  In March 2022, JDRF announced that they would work with a non-profit, Civica to manufacture low cost insulin.  In June, California announced that it would manufacture low cost insulin.  Finally, in March 2023 California  announced that they had signed a contract with Civica to manufacture insulin which would be distributed by CalRx for $30.  During this same time, the US Senate passed a law capping insulin copays at $35/month for medicare patients, and several states also passed laws limiting insulin costs in various ways.

So the three commercial insulin manufacturers had little choice and dropped their prices by 90%. 

Discussion

A full discussion of this will take much more space than I have here. However, the very quick summary is that we have seen a huge "market distortion" for decades in the price of insulin. The insulins available have not changed in decades, their manufacturing has not changed, and yet their price (adjusted for inflation) has gone up very steeply and steadily. This is the exact opposite of what a market economy should do.  If you look at the price changes (shown below) it is pretty clear that the companies involved have realized that they can make more money by raising prices when their "competition" does, rather than actually competing with them. 

But now we have a non-profit, with seed funding from the state of California, and the support of JDRF, competing with the three existing corporate insulin manufacturers.  Just a few months after this competition was announced, all three of the corporate manufacturers have announced huge price cuts.  My guess is that California (as a state) will end up cash positive before they even start distributing their insulin.  The citizens of California will already have saved more money on insulin than California used to fund Civica.  JDRF will be in even better shape, since their "cost" was only in publicity, lobbying, and coordinating, but (again) their membership will save real money every month.

For me, this is an interesting experiment.  The last few decades have shown very clearly that the free market does not work for life-saving products when there are only a small number of manufacturers.  Even economists understand that the free market does not work when there is a monopoly, but it is clear from the price of insulin, that it does not work for 3 companies, either.  With 3 manufacturers, they learn that they can make a lot more money by not competing, than by competing.  So that is what they do.  As we move forward, we will see if 3 for-profit manufacturers and 1 non-profit/public-good manufacturer create a better market for society as a whole.

The big insulin manufacturers themselves claim that their profits motivate new breakthroughs and better products.  This is obviously untrue for insulin.  No actual improvements in insulin have been marketed in over a decade.  Lantus was approved in 2000; Levemir in 2005, Humalog in 1996, and  Novolog in 2000.  

From California:
https://www.healthcaredive.com/news/California-manufacture-insulin/626916/
https://www.gov.ca.gov/2023/03/18/governor-newsom-announces-30-insulin-through-calrx/
From JDRF:
https://www.jdrf.org/press-releases/jdrf-announces-support-of-civica-to-manufacture-and-distribute-low-cost-insulin/

Sanofi Buys Provention (And Other Tzield News)  

Provention is the company that just got FDA marketing approval for Teplizumab / Tzield for people at risk of T1D.  The new news is that Sanofi is buying Provention. Obviously, Sanofi is a very large "big pharma" company, and Provention is a small "boutique" drug development company.  I'll leave it to the business analysts to comment on this, but it is very common for big pharma companies to buy boutique drug developers when they have a successful product, so this should not surprise anyone.  I would not expect anything to change for Teplizumab, but only time will tell with certainty.  

In the long term I think this is good for T1D cure creation in general.  Sanofi is paying good money for Provention, and that will motivate future investors and future executives to try to find disease modifying treatments for T1D.  These guys made a huge pot of money doing exactly that.  The stock price went up about 350%.  That should motivate people!

One comment I've often heard in the years since I started the blog, is that companies that make a lot of money off of T1D are not going to invest in cures.  This is not exactly that, but it is pretty close.  Sanofi makes a lot of money off of insulin (see above), and Tzield should delay the start of that revenue stream in people who use it, and yet they still were willing to put a lot of money in Provention.  And if they now kill it, that will be pretty obvious and very public.   Sure they could do it, but not in secret.

Put another way, over the last 6 years, about 1/2 billion dollars have been invested in Provention, and it is now worth about 3 billion.  That is great return on investment!  Those investors will want to do that again, if they get the opportunity.

News coverage: https://www.reuters.com/markets/deals/frances-sanofi-acquire-us-based-provention-bio-29-bln-2023-03-13/

Other Provention/Tzield News

I've learned a few more things about Tzield:

• A few people have gotten the Tzield in the Sacromento area, and a few people are about to get it in the San Francisco area.  In all cases, the treatment was covered by their insurance.
  
• About half the people who get it get "flu like" symptoms, which last a few weeks.
• Because it requires an infusion every day for 14 days, and these are done in clinics, you need to have access to a clinic which is open 7 days a week, and you need the time and transportation to get there. 
  

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 daughter has type-1 diabetes and participates 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.

 

Results from a Phase-II Verapamil Study

Verapamil is a drug which has been used in the US since 1982 for high blood pressure, migraines, and heart problems.  It also lowers levels of a protein called TXNIP.  Some researchers believe this is important because they believe TXNIP kills beta cells as part of the onset of type-1 diabetes.  So giving Verapamil should lower TXNIP which should improve beta cell survival, and stop type-1 diabetes.  In addition TXNIP is pro-inflammatory, so lowering it should lower inflammation, which could also have a good effect on type-1 diabetes. Verapamil has already undergone phase-II trials for T1D in the United States, which I discuss below.

You can read my previous blogging on Verapamil here:
https://cureresearch4type1diabetes.blogspot.com/search/label/Verapamil

What Were The Results?

The summary is that, after one year, people who got Verapamil generated 30% more insulin, than people who did not.  However, it is important to remember, that one year after diagnoses, most people with T1D are generating almost no insulin at all.   So 30% of almost nothing is a pretty small difference between the Verapamil and non-Verapamil groups.

Over the years that I have been following honeymoon clinical trials, there have been a couple of treatments which, when measured after a year, the treated people were generating twice as much insulin as the untreated people.  So a bigger difference than seen here.  However, twice a very small amount is still a very small amount, and none of these treatments have become successful from such a small starting point.

JDRF's report: https://www.jdrf.ca/exciting-news-new-drug-in-clinical-trials-shows-slowed-type-1-diabetes-progression-in-newly-diagnosed-children-and-teens/?utm_source=ENTwitterVerapamil

News Coverage:
https://www.medscape.com/viewarticle/988806?src=soc_tw_230228_mscpedt_news_endo_diabetes&faf=1
https://jamanetwork.com/journals/jama/fullarticle/2801974

This Study: https://www.clinicaltrials.gov/ct2/show/NCT04233034

Other Verapamil Studies

A previous, smaller study found that Verapamil treated people generated 40% more insulin after a year.  So pretty similar to these findings.

Previous Verapamil Study: https://www.clinicaltrials.gov/ct2/show/results/NCT02372253

There is a third study underway, covering 138 people and expected to finish in February 2024.  I blogged about that one last year:
https://cureresearch4type1diabetes.blogspot.com/2022/02/verapamil-sr-starts-phase-ii-trial-ver.html

Another Verapamil Study: https://www.clinicaltrials.gov/ct2/show/study/NCT04545151

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 daughter has type-1 diabetes and participates 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.

Influenza Vaccination Starts a Phase-II? Clinical Trial

This is a straight forward clinical trial: people recently diagnosed with type 1 diabetes (in their honeymoon phase) will be given a standard flu vaccine to see if they will generate more of their own insulin as compared to people who don't get the vaccine.  They are using a Sanofi Pasteur vaccine, VaxigripTetra™, which has been used for over 6 years in people 3 years and older.  Previous versions of this vaccine have been in widespread use for decades.

They are recruiting 100 children (between 7 and 17) who have been recently diagnosed with T1D.  This study is a standard, high quality study: it is blinded, randomized, and has a placebo control group.  The primary end point is a C-peptide measurement (showing how much insulin the person is naturally producing), and there are several secondary and tertiary end points covering both patient results and internal immunology results.

They plan on gathering almost all of their data in the first year, but will monitor participants for safety issues for 5 years.  This study started in Dec-2022 and they hope to finish in June-2026. 

They are recruiting at four hospitals in Denmark: Aarhus University Hospital, Aarhus, Aalborg University Hospital, Randers and Gødstrup regional hospitals.

Contact: Ole Frøbert, MD, PhD ole.fro@clin.au.dk
(There is additional contact information in the clinical trial registry.)

More Information

Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT05585983

Discussion

For me, there are two interesting discussion points (and one uninteresting discussion point).

The obvious question is: why do the researchers think it will work? 

The researcher, Ole Frøbert, recently published a study showing that flu vaccine administered shortly after a heart attack reduces the ongoing risk of death.  Heart attacks come with high levels of inflammation and he believes that flu vaccination lowers this inflammation, causing the good outcome he saw.  While flu vaccination raises immune response in general, it also lowers specific inflammation signalling. It is well known that in T1D inflammation is an important path for the destruction of beta cells, causing the start of the disease (or at least the start of the symptoms and the need to inject insulin).  This researcher believes that flu vaccination lowers inflammatory signaling for the specific targets which are doing the damage in T1D.  These targets are discussed in the following paper:  https://pubmed.ncbi.nlm.nih.gov/34326232/

I have not found any previous research testing if flu vaccines have any impact on existing T1D.

But there is good evidence that people with T1D get flu more than others, which is why people with T1D should get yearly flu vaccinations.  A recent summary is here:  https://www.frontiersin.org/articles/10.3389/fimmu.2021.667889/full and recommendations to do so from the CDC and the ADA are linked here: https://www.healthline.com/health/diabetes-and-flu-shot.

There are also many studies showing that flu vaccines do not cause T1D and are safe for people with T1D.  I have summarized these studies here:
https://cureresearch4type1diabetes.blogspot.com/2015/10/seasonal-flu-vaccine-and-type-1-diabetes.html
and here is the statement from the US National Academies of Science, with many supporting links:
https://www.nationalacademies.org/based-on-science/is-it-possible-for-the-flu-shot-to-cause-type-1-diabetes

The big issue for me, for this trial is: should I blog on it?  Is this research aimed at a cure or are they just hoping for better control, maybe using less insulin?  I blog on the first kind of research, but not the second.

When it is not clear if the researchers are aiming for a cure or a treatment, I look at what they are measuring as their primary result.  C-peptides are a measure of insulin production, so if that goes up, it can (at least potentially) lead to a cure.  On the other hand, blood glucose levels, A1c, and insulin usage are all treatment-oriented measures.  For this study, the primary outcome measure is C-peptides, so I'm treating it as cure focused.  They are also measuring blood glucose, A1c, and insulin levels, so if it turns out to have results that help treatment (but not cure), then I'll stop covering it.

The investigators certainly do not expect that the influenza vaccination will cure type 1 diabetes in this trial.  However, even a modest improvement in insulin generation would suggest a new research direction into a possible, future, vaccine based, cure.

The uninteresting discussion point is this: will it work?  

The answer is simple: we don't know; that is the whole purpose of this trial.  Since the trial is fully funded and underway, there is no reason to speculate as to whether or not it will work.  All we need to do is wait and see.  Guessing as to outcomes is a waste of time.

Note: I classify this study as phase-II? because it is the size of a phase-II study, but the treatment has never been tested on people with T1D.  Therefore, there is no T1D data available from a phase-I study, so I call it "phase-II?".  Officially, it is phase-IV, because it is being done after the vaccine is on the market. 

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 daughter has type-1 diabetes and participates 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.

 

Ixekizumab (Taltz) Starts a Phase-II? Trial In Honeymooners

Ixekizumab, sold under the trade name Taltz, blocks a specific part of the immune system called Interleukin 17 (IL-17).  It has been approved since 2016 in the US and the EU as a treatment for Plaque Psoriasis and Psoriatic Arthritis in people 6 years old or older.  Over 120,000 people have used it.

The researchers believe that Type 1 Diabetes and Psoriasis are similar diseases, and since Ixekizumab has been effective in treating Psoriasis, they hope it will be effective for T1D as well.  This is a quote from their clinical trial registration: 

Psoriasis share several aspects with T1D, e.g. the patchy inflammatory infiltrate consisting of tissue-resident memory (TRM) T cells, leaky blood vessels that facilitate leukocyte migration and the increased risk for systemic conditions. Moreover, interleukin (IL)-17 has shown to be increased in both persons with psoriasis and T1D. Activation of IL-17/IL-22 pathway is viewed to be both a hallmark of psoriasis and human T1D. Ixekizumab, an anti-IL17 biological agent, has shown marked therapeutic value in the treatment of subjects with psoriasis in several randomized trials and is currently an approved clinical therapy. Due to the many similarities in the current view of pathogenesis and manifestation of T1D and psoriasis it is possible that Ixekizumab can also influence the disease process of T1D.

The Study

This study is open to adults (18-35) who are in their honeymoon phase (within 100 days of diagnosis).  They plan to enroll 127 people, and the study will follow them for a year to get primary data, but then continue to follow them for an additional 3 years for extended data.

Patients will get two injections (subcutaneous, much like insulin) the first week, and then one injection every other week for 12 weeks, and then monthly injections for the rest of the year.

The primary end point is C-peptide, which measures how much insulin a person is producing.  Secondary end points include insulin dosage, A1c, time spent in range, and time spent low.  There are 13 other end points being measured as well.

They are recruiting in Sweden at 4 sites right now (Södra Älvsborg Hospital, Sahlgrenska University Hospital, NU-Hospital Group, and Uppsala Academic Hospital), but plan on expanding to 19.  There are two contacts:

• Marcus Lind, MD, PhD       +46(0)766-183142    marcus.lind@gu.se
• Shilan Seyed Ahmadi, MD                                    shilan.seyed.ahmadi@vgregion.se   

This study started in November 2022 and they hope to finish in 2027.

Clinical trial registry: https://clinicaltrials.gov/ct2/show/NCT04589325

Discussion

One question that comes up with research on commonly used drugs, like this one, is "T1D is relatively common, so if it helps, and it has been used on so many people, why hasn't anyone noticed?"  There are two answers to this question:

The first answer, at least in the United States, is that there is no central database of medical records, so there is no easy way to see if this is happening, and it is unlikely any doctor would notice in their own patients.  For example, if 120,000 people have used this drug in the world, then maybe 40,000 of them are in the US.  If about 1 in 400 people in the US have T1D, then this drug has been used on about 100 people with T1D.  

For an individual doctor, they are unlikely to have more than 1 patient who has T1D and is taking this medicine, so unless the results are really extreme, the doctor will see it as just the natural variability of the disease.  They are unlikely to see a pattern, because they are unlikely to have even 2 patients in the same situation.  After all, there are only about 100 such patients in the whole of the US. 

However, there is no way to get get medical data on these 100 people, not even anonymously, and there is no way to even find out which 100 people it is.  Some European countries do have these kinds of medical record databases, and they sometimes do publish this kind of research.  However, their populations are much smaller, so the number of people reported on would be smaller as well. 

In the last few years, we have moved, slowly, toward better medical record databases.  For example, I have seen studies based on Kaiser's medical record database.  Kaiser is unusual in that it is both an insurance company and a medical provider with its own hospitals, clinical, and staff.  Therefore, it has the medical records, the motivation for improvement, the infrastructure, and the large scale, needed for this kind of record based research.  

The second answer is that this is not likely to be a sudden cure at the standard dosage.  Because that would, indeed, be too obvious.  If people took the standard dose and were suddenly cured, even just once, some doctors would notice.  However, it still may be true that this helps T1D, that it encourages insulin production, and can lead to a cure in a different dosage than currently given.  

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 daughter has type-1 diabetes and participates 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.

 

OPT101 Starts A Phase-I Trial in Adults with Established T1D

OPT101 is a peptide derived from mouse CD154.  What does that mean?  A peptide is a small part of a protein.  CD154 is a protein found on some immune cells in both mice and people.  CD154 is also called CD40L, but must not be mixed up with CD40. CD154 and CD40 work together to regulate parts of the immune system.

You can think of the immune system as being a large collection of different cells, often with CD or IL names.  These cells interact in various ways to attack (or ignore) certain cells.  Many immune responses are controlled by a balance between two different types of cells.  This is the relationship between CD154 cells and CD40 cells.  They balance each other so the the immune system is aggressive enough to attack foreign cells, but not so aggressive as to attack the body's own cells. 

The researchers involved have been looking at the balance between CD154 and CD40 as part of the  pathway to T1D for at least 20 years.  There is a lot of research showing that CD154 (and the relationship between CD154 and CD40) is important to the path that leads to T1D.   Therefore, it makes a lot of sense to test drugs that impact CD154.

The Clinical Trial

This is a Phase-I study of 18 people, but blinded, randomized, and placebo controlled study (so high quality).  I think of it as the size of a Phase-I trial, but the design/quality of a phase-II trial.  2/3s of the people will get the OPT101 treatment, 1/3 a placebo.  People in the study must be adults under 60 years old, who have had T1D for 20 years or less.  This trial is for people with established T1D, not just honeymooners.

The study is divided into two groups, which differ by dosage.  The second group will get about twice as much as the first group.  Each group will have 6 people who get the treatment and 3 who get the placebo. 

This study started in Sept-2022.  The paperwork says they hope to finish by Oct-2022, but that is obviously a mistake.  If they run both of their groups at the same time, they might be done by mid 2023, or by early 2024 if they run them one after the other.

They are currently recruiting at two locations on the US West Coast:
Contact: Lisa Boswell, MS     303-503-9954     LB@op-t.com    

Diablo Clinical Research Center, Walnut Creek, California, United States, 94598
Contact: Meaghan Saint, PA-C, CDCES       msaint@diablolclinical.com   
Contact: Catherine Morimoto       cmorimoto@diabloclinical.com   

Rainier Clinical Research Center, Renton, Washington, United States, 98057
Contact: Sarah Holtz    425-251-1720 ext 309    sholtz@rainier-research.com   
Contact: Tina Mitchell, RN    425-251-1720 ext 313    tinam@rainier-research.com  

Discussion

Two quick points:

The thing I like most about this trial is, because they are gathering data for only 3 months, we will have results quickly.

Another company, Eledon Pharmaceuticals, is also targeting CD154 (which they refer to as CD40L), and they registered two clinical trials for AT-1501.  However they withdrew the registration before the studies started, and in any case, they were targeted at helping islet cell transplants and not directly curing T1D.  

More Information

Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT05428943
Company Web Site: http://op-t.com/
Background: https://www.frontiersin.org/articles/10.3389/fendo.2017.00208/full

 

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 daughter has type-1 diabetes and participates 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.

 

Youtube Video Describing How JDRF Makes Funding Decisions

If you care about research aimed at curing type-1 diabetes, then you should care about JDRF's research funding.  Year after year, they fund more than 2/3s of the research in clinical trials aimed at curing type-1 diabetes. (See my yearly "JDRF Funding for a Cure" blogs for details.)

This Youtube video:
https://www.youtube.com/watch?v=ARbbeAe8ky8
is an official JDRF video describing (at a high level) how they make decisions about what research to fund.  It is well worth 35 minutes of your time.  Do not stop watching when the DEI section starts.  That section is interesting in its own right, but also, after it is another section going into more details about JDRF decision making.

 

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 daughter has type-1 diabetes and participates 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.