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!
