Siplizumab Starts Two Trials in Honeymoon T1D (DESIGNATE and STRIDE)

Siplizumab (MEDI-507, TCD601) is an monoclonal antibody which targets CD2 cells in the immune system.  It is being developed by ITB-MED.  It has an active research program for several different diseases with about 20 clinical trials in process.  There are currently two clinical trials targeting Type 1 Diabetes, so I'll discuss each in turn.

Part of the motivation to test Siplizumab was a previously good result from Alefacept.  I blogged about that result here:
https://cureresearch4type1diabetes.blogspot.com/2016/02/alefacept-reports-on-phase-ii-results.html
You can read my conclusions in the previous blog posting, but the company that made Alefacept stopped marketing the drug, which had been approved for Psoriasis, because of newer drugs in the field.  The hope is that Siplizumab will work in the same way and have similar results.

DESIGNATE: Phase-IIΔ Siplizumab in [Mostly] Honeymooners

This trial was started by the US government (National Institutes of Health, National Institute of Allergy and Infectious Diseases) and is being run by the Immune Tolerance Network.  It started in April-2023 and they are enrolling 120 people, which is a lot.

Initially adults were enrolled, but later the study started enrolling children as young as 8.  Everyone is within 18 months of diagnosis.  This is an open label trial, where each person will get one of four different doses of Siplizumab.  No placebo or control group.

The primary end points for this study look at changes in immune cells, so they are measuring how the treatment changes the immune system.  The secondary end points include adverse effects, C-peptides, and insulin use, and so cover both safety and effectiveness.

This study is in a pause right now.  They are evaluating the results from the first couple of people, and may change the study slightly based on what they learn.  When it moves forward, they will be recruiting at 20 locations all over the US, which will be listed in the links below:

Trial Web Page: https://www.designate-study.org/
Clinical trial registry: https://clinicaltrials.gov/study/NCT05574335

STRIDE: Phase-IIΔ Siplizumab in Honeymooners

This trial was started by a company (ITB-Med LLC), and is run by INNODIA.  It started in Jan-2023 and expects to finish in Jan-2025.  They are enrolling 96 adults. 

People must be within 100 days of diagnosis to be enrolled.  I think that there are four treatment groups, with one getting a placebo and the other three each getting a different dose of Siplizumab.  Nowhere are the doses listed.  Patients will get the treatment for 12 weeks; I think 1 dose per week, and will be followed for a year total. 

Although the description is a little vague, I think this study measures C-peptide as its primary end point, and adverse reactions as its secondary end point.  The first covers effectiveness and the second covers safety.

This study is still recruiting in Europe (Belgium, Germany, Italy, Poland, UK).  You can see the exact locations in the clinical trial registry: https://clinicaltrials.gov/study/NCT06025110

Eudract number: https://www.clinicaltrialsregister.eu/ctr-search/trial/2022-001713-39/SE

Discussion

These clinical trials have a lot in common.  The differences I do see are:

1. The STRIDE study recruits people within 100 days of diagnosis, while DESIGNATE recruits people within 18 months of diagnosis.
2. The STRIDE study recruits adults only, while DESIGNATE started out recruiting adults, but later added children.
3. STRIDE is single blind, DESIGNATE is open label. 
4. My understanding is that the two studies use different dosing techniques. 
   

An obvious question is: why did two different studies start at almost the same time, which are so similar?  I don't know the answer.  Both studies were motivated by the same company, the one producing the drug, and I'm always in favor of doing more studies, more quickly.  I'm happy they are moving forward along two separate paths at the same time.

One issue in the DESIGNATE trial is the recruitment cut off of 18 months after diagnosis.  I don't understand that.  The honeymoon time period is generally accepted to end after 12 months or a little earlier, so this means that DESIGNATE will include some honeymooners and some non-honeymooners.  I can only hope that they will analyze the data for both people recruited in their honeymoon phrase and separately for people who are not, just in case it works at one time but not at the other.

I'm not sure of the details of the history of Siplizumab, but I think it was originally developed by MedImmune,which was later bought by AstraZeneca.  However, the rights were later bought by ITB-Med, who are responsible for testing the drug on people with T1D. 

The Immune Tolerance Network, which is running DESIGNATE, is a collaborative network for clinical research, funded by the National Institute of Allergy and Infectious Diseases, part of the [United States] National Institutes of Health (especially through the special type 1 diabetes appropriation), and JDRF.

INNODIA, which is running STRIDE is a European non-profit network dedicated to preventing and curing type 1 diabetes.  It is funded by the European Commission’s Innovative Medicines Initiative (IMI-JU Joint Undertaking), The Hemsley Charitable Trust, JDRF, and EFPIA partners.

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 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!

Why I Don't Blog On How To Vote For T1D (part 1)

This whole blog posting is very US (and US politics) focused, but the issues are similar in other countries.  Also, this blog is trying to describe the existing situation, not argue that the current situation is good, bad, or should be changed.  It is just describing how things are.

When I first starting blogging, over 15 years ago, I thought it might be a useful idea to have a "Voter's Guide To T1D" style blog.  I would discuss who to vote for if all you cared about was T1D, why one candidate was the best for T1D research, how your vote would impact T1D research, and so on.  I never quite got around to it.  Since then, I've changed my opinion and decided that such a blog could never be written because T1D should not effect how people voted.

As people affected by T1D, we should want two things from our government, which means two things to consider when we vote.  One is the best possible care for T1D and the other is the best possible research into finding a cure for T1D.  Some people are more care focused, and others more cure focused, but those are the biggest T1D issues out there.

The democratic way to view this is to ask the question:  "if T1D is important to me, who should I vote for to improve these things."  The idea is that your vote should be directed by what you care about.  My insight is that is not true, because your vote is actually about how to solve problems, not what problems are important.

For example, consider research.  In the US, more liberal people think that research can be encouraged by funding research.  More conservative people, by lowering regulation of research. Neither of these groups are for or against research, they differ on how to encourage it.

Obviously, the perfect person to vote for is someone who cares about T1D and who has the same political leanings as you, and obviously the worse person to vote for is someone who doesn't care about T1D and has the opposite political leanings as you. 

However, in choosing between someone who has your political leanings, but does not care about T1D and someone who does not have your political leanings, but cares a lot about T1D, who should you vote for?  The answer is: you should choose the person with your politics.  (And this is true even if you are a single issue voter, and that issue is T1D.)

Why?  Because the person who does not share your politics will do things that they think will help T1D, but you will not agree with, even for T1D.  For example, if you are a liberal who cares about T1D, but vote for a conservative because they care a lot about T1D, they are going to lower government regulations on big businesses.  And you are going to think, it just encourages businesses to fleece me and not do any more research. 

Therefore, you should vote your own politics and not vote for who "cares" more about T1D, unless it is a primary and both politicians have your politics in general, and it is just a question of more or less T1D.  If you have that luxury, definitely vote more T1D!  However, that assumes the choice is between to people who otherwise share your views.

In the past, there might have been politicians who were generally liberal, but conservative on T1D research, or the other way around, so you might want to vote for them because they matched your T1D views, even if they did not match your more general views.  But I think those politicians are rare to nonexistent today.  Today, politicians are either liberal about nearly everything or conservative about nearly everything.

So therefore, blogging about a particular politicians positions on T1D is a waste of time.  The important thing is their general politics, and others can blog on that much better than I can.

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 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.