IMCY-0098 Starts a Phase-I Clinical Trial

I always enjoy blogging about a clinical trial for a new treatment, done by a new company, which hopes to cure type-1 diabetes. As I understand it, Imcyse, the company doing this research, has a method for creating peptides (small pieces of a protein) which will generate a type of immune cell that is able to destroy the immune cells of the body responsible for the disease. If this works, they can specifically target the cells that are causing autoimmune diseases. The company is going after Type-1 Diabetes (first), Multiple Sclerosis (second), and several other diseases after that. IMCY-0098 is the code name for their peptide targeting T1D.

IMCY-0098 Starts a Phase-I Clinical Trial

This study started in Aug 2017 and they hope to finish in Dec 2018.  They will enroll a total of 40 adult honeymooners (within 6 months of diagnosis) divided up into three groups. In addition to their regular insulin treatments, each group will get a total of 4 injections over 2 months (just below the skin, like an insulin injection).  One group will get low dose injections, one group medium dose injections, and the third group will get high dose injections; and each group will contain some controls who will get a placebo.  Patients will be followed for 6 months.  The researchers will track safety issues, effectiveness (C-peptide, A1c, etc.), and changes in the immune system.

They are currently recruiting in Belgium, Denmark, Cardiff and Oxford, and plan to start soon in France, Germany and additional location in the UK.  The list is long, and you can see the exact locations in their clinical trial record: https://clinicaltrials.gov/ct2/show/NCT03272269

Company Web Site: http://www.imcyse.com/en
Trial Web Pages (in different languages):
http://www.bdronline.be/index.php?n=169&id=267&sid=267&taal=F&mnav=2
http://www.bdronline.be/index.php?n=164&id=265&sid=265&taal=N&mnav=2
Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03272269
Most recent full paper / Results In NOD Mice:
http://www.imcyse.com/upload/documents/publications/Abrahimians-2016.pdf
Some more web sites:
https://www.type1diabetesresearch.org.uk/current-trials/ (Exalt study)
http://www.address2.org/t1d-studies/ (Exalt study)

Discussion

The company's web site includes this page:
http://www.imcyse.com/en/technology-platform
which discusses how they are developing their treatments.  Unfortunately, it is too technical for me to understand.  But for readers with a background in immunology, this page might be valuable.

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.

Possible Cures for Type-1 in the News (November)

Merck Cancels "Smart Insulin" (MK-2640) After Unsuccessful Phase-I Trial

This is the news everyone hoped we would not get.  After completing a phase-I trial of "Smart Insulin" (also known as MK-2640), Merck has decided not to move forward with it.  They have not published the results, but have published this: "MK-2640 was discontinued due to lack of efficacy".

News report:  http://www.pharmaceutical-journal.com/news-and-analysis/features/towards-a-smarter-insulin/20203828.article

Discussion

This was the first (and so far only) glucose responsive insulin to be tested in humans.  However, there are several "smart insulins" being tested in animals, not to mention "smart artificial cells" and "smart membrane" based technologies, all aimed at automatically regulating the amount of insulin in the blood stream.  I expect some of these to enter human trials in the next few years.  So "smart insulin" may yet be a trail blazer, even if it itself was unsuccessful.

If results from this study are ever published, I'll blog on them here.  However, there is nothing forcing Merck to publish these results if they don't want to.

Phase-II T-Rex Trial Update

Caladrius Biosciences recently announced that they had enrolled the 70th patient (out of 111) in their clinical trial of CLBS03 for T1D.  So it has taken them roughly 18 months to recruit 2/3 of the patients they need.  If they can keep up that pace, they will finish recruiting in the third quarter of 2018, and finish collecting data in the third quarter of 2019, and publish in 2020.

Previous Blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/Polyclonal%20Tregs

A quick summary of this treatment is as follows: remove one specific type of T regulator cell (called "CD4(+)CD25(+)CD127(lo)") from a person with type-1 diabetes.  Grow them out so you have about 500 times more, and then put them back in the same person.  Since regulatory T cells naturally regulate the body's immune system, and the patient now has more of them, the hope is that they will prevent the autoimmune attack which causes type-1 diabetes.

They are recruiting patients in about 15 locations all over the US, so read the clinical trial registry to get a complete list and some contact information.

News Report: https://www.caladrius.com/press-release/caladrius-biosciences-announces-enrollment-of-the-70th-subject-in-the-phase-2-t-rex-clinical-trial-of-clbs03-for-type-1-diabetes/
Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT02691247

SIMPONI (Golimumab) Starts A Phase-I Trial In Pre-Symptomatics

Golimumab (sold as Simponi) is an immune system modulator, which has been approved in the United States and many other countries for treatment of several autoimmune diseases, so testing it on type-1 diabetes makes a lot of sense.  This is the second trial underway for this drug.  (The other one is called T1GER, and is for honeymooners.)  Simponi has already been approved to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and ankylosing spondylitis.

This study is recruiting people who have two autoimmune antibodies (but no other symptoms of type-1 diabetes). They are recruiting 30 kids (aged 6-21), and will follow them for 17 months. Each kid will get 26 weekly injections.  Half the patients will get Simponi and the other half will get a placebo.  They hope to finish this study in mid 2021.

This study is current recruiting in Linkoping University Hospital, Linkoping, Sweden, SE 58185.
Study contact: 844-434-4210 JNJ.CT@sylogent.com
They hope to start recruiting at other locations in Sweden and Finland soon.

The unusual thing about this trial is that they will not measure any effectiveness data at all.  The only data gathered will be safety and side effect data.  No C-peptide data, no A1c, or insulin usage.  That's very unusual for a type-1 diabetes study.  In my experience, even the phase-I studies gather some effectiveness data.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT03298542
Previous Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02846545

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 Phase-I Clinical Trial of Proinsulin Peptide Vaccine in Honeymooners (MonoPepT1De)

For over 10 years there has been a research group at Cardiff University (UK) working on creating vaccine-like treatments to cure or prevent type-1 diabetes, and this blog posting covers their recent results.

As background: one of the autoantibodies that is associated with type-1 diabetes targets insulin molecules [d1]. Therefore, there is a theory that giving people with T1D a protein fragment from insulin might prevent or delay the onset of type-1 diabetes.  It would train the body not to produce this autoantibody. The process is vaguely similar to giving small amounts of peanut proteins to people with peanut allergies [d2].  These researchers are using a peptide (a small part of a protein) from proinsulin, which is a precursor of insulin.

Results From Phase-I Clinical Trial of Proinsulin Peptide Vaccine in Honeymooners

This trial involved 27 people divided into three groups.  One group got a placebo and was a control group, the other two groups got the Proinsulin Peptide injections for 6 months.  One group got the peptide every 2 weeks, the other every 4 weeks.  The people were adult, honeymoon diabetics (within 100 days of first insulin injection).  They will be followed for 3 years, although this publication only covers the first year after treatment.

The untreated group went through a normal honeymoon period, where over time they gradually generated less and less of their own insulin, and had to inject more and more.  However, the treated people (on average) held steady in their ability to generate their own insulin, and did not lose their ability to generate insulin for the time covered. So this meant that the treated group did better than the untreated group over time, and the difference was statistically significant.  Also, there were no safety issues.

JDRF funded this trial specifically, and this whole line of research, in general.

News Coverage:
http://www.medicalnewstoday.com/articles/318899.php
http://www.latimes.com/science/sciencenow/la-sci-sn-diabetes-immunotherapy-20170809-story.html
Abstract: http://stm.sciencemag.org/content/9/402/eaaf7779
Full Paper: http://stm.sciencemag.org/content/9/402/eaaf7779.full
Clinical Trial Record:  https://clinicaltrials.gov/ct2/show/NCT01536431

Discussion

I think there are three important points for this research:

First, these results are good enough to spur a phase-II trial, and the Cardiff researchers have already made it clear they hope to run a phase-II trial starting in 2018.  Two of the authors of this paper are consultants to UCB Pharma to help design that trial.  So that is good.

These results join a growing number of treatments with what I call "medium good" results in honeymooners.  "Medium good" means that the treated group did not get worse, but did not improve either.  This is in comparison to the untreated group which did get worse.  (During the honeymoon phase, people with type-1 diabetes get worse: they gradually lose the ability to generate insulin.  They go from generating a little insulin, to generating none.)  I think there are about half a dozen treatments which have phase-I or phase-II? results of this type.  So it's better than nothing, but because none of these treatments have moved forward to even better results, I'm not not particularly excited about them.  I'm still hoping for better results in future trials.

These "medium good" results may become even more valuable in the future, if they can be applied to people in the earliest stages of type-1 diabetes, when they have two autoantibodies, yet are not showing any other symptoms.  I'm hopeful that preserving insulin generation at that level could delay or prevent needing injections completely.

Second, this same research group is working on another clinical trial closely related to this one, but it has not gotten as far along the development path: https://clinicaltrials.gov/ct2/show/NCT02837094  (This is an 8 person clinical trial without a control group.)

Finally, this same research group is working on a similar treatment, but based on many peptides, rather than just one.  That trial is called MultiPepT1De:
https://clinicaltrials.gov/ct2/show/NCT02620332
They completed recruiting on 3 July 2017, so should finish gathering data about the end of 2017.

Details

[d1] Autoantibodies are the malfunctioning antibodies which cause the immune system to attack beta cells. There are five autoantibodies associated with type-1 diabetes, and there may be more that we haven't discovered yet. The five we know about are:
* micro insulin autoantibodies (mIAA or just IAA)
* islet-cell antibodies (ICA)
* glutamic acid decarboxylase (GAD) antibodies
* islet antigen-2 (IA-2) antibodies
* zinc-transporter 8 (ZnT8) autoantibodies

[d2] It is important to realize that type-1 diabetes is NOT a conventional allergy to insulin. It is similar to allergies in that it is the body's immune system overreacting to something that it should not react to, but other than that, is quite different. Allergies involve the immune system overproducing histamines. These histamines attempt to get physical irritants, like pollen, out of your body. You can counter this histamine reaction by taking antihistamines. Type-1 diabetes involves the immune system overproducing malfunctioning killer T-cells (or perhaps under producing regulatory T-cells). These malfunctioning killer T-cells mistakenly kill beta cells, thinking they are foreign cells (ie. living creatures like viruses, that have invaded the body). So the mechanism is different (histamines vs. T-cells), and the mistaken target is different (physical things, like pollen or wheat vs. living organisms, like viruses).

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.