SAR446268 for Myotonic Dystrophy

(BrAAVe Trial)

Recruiting at 6 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sanofi

Must not be taking: Antivirals, Corticosteroids, Anti-myotonics

Disqualifiers: Liver disease, Renal disease, Respiratory insufficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SAR446268 for individuals with myotonic dystrophy type 1 (DM1). Researchers aim to determine if a single dose can safely lower certain protein levels linked to DM1 and improve muscle function. The trial includes different groups receiving increasing doses to identify the safest and most effective amount. Individuals diagnosed with DM1, who experience muscle stiffness and weakness, and can walk 10 meters independently might be suitable candidates. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that participants stop taking anti-myotonic medications and systemic corticosteroids at doses greater than 5 mg/day at least 15 days before starting the study. If you are on these medications, you will need to stop them before participating.

Is there any evidence suggesting that SAR446268 is likely to be safe for humans?

Research has shown that SAR446268 holds promise in early testing. In studies with animals similar to humans, the treatment was well-tolerated and successfully lowered levels of a specific protein linked to myotonic dystrophy. This finding suggests the treatment might also be safe for humans.

The FDA has fast-tracked this treatment for non-congenital myotonic dystrophy type 1. While this does not guarantee safety, it indicates potential and hope for quicker development due to early promising results.

This clinical trial is in both Phase 1 and Phase 2 stages, focusing primarily on the safety of SAR446268 for humans. These phases are designed to monitor side effects closely and ensure the treatment's safety. Although detailed human data is not yet available, ongoing research is essential to confirm the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

SAR446268 is unique because it offers a new approach to treating myotonic dystrophy, a condition traditionally managed with symptomatic treatments like physical therapy and medications for pain and fatigue. This investigational drug is exciting because it targets the underlying genetic causes of the disease, potentially altering its progression rather than just alleviating symptoms. Researchers are optimistic about SAR446268 because it could provide more effective and long-term relief, improving the quality of life for those affected by this condition.

What evidence suggests that SAR446268 might be an effective treatment for myotonic dystrophy?

Research shows that SAR446268, the investigational treatment in this trial, may help treat non-congenital myotonic dystrophy type 1 (DM1). Earlier studies found that SAR446268 can lower levels of DMPK mRNA, a molecule linked to DM1 symptoms. High levels of this molecule can cause muscle problems in people with DM1. SAR446268 aims to reduce these levels, potentially improving muscle function. The treatment has received a Fast Track designation, highlighting its potential and the need for effective DM1 treatments. Initial results suggest it is safe and effective, but further research is needed to confirm these findings. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for males and females aged 10 to 50 with non-congenital myotonic dystrophy type 1 who can walk at least 10 meters. They must have a genetic diagnosis of DM1, show signs like muscle weakness, and may have a pacemaker or ICD if they're in Part A of the study. Those under age restrictions or with certain cardiac risks are excluded.

Inclusion Criteria

I have been diagnosed with DM1, showing symptoms like muscle stiffness and weakness.

My DM1 condition developed after birth.

I have a genetic diagnosis of DM1 with a CTG repeat length of 50 or more.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive a single intravenous (IV) administration of SAR446268

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SAR446268

Trial Overview The trial tests SAR446268, a gene therapy delivered through IV to reduce DMPK mRNA levels and improve neuromuscular function in DM1 patients. It includes dose escalation (Part A) to find an effective dose followed by expansion (Part B), lasting approximately two years per participant.

How Is the Trial Designed?

Group I: SAR446268 Experimental Treatment 1 Intervention

Participants will receive a single dose of SAR446268 on Day 1

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Citations

1. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-09-23-05-00-00-3154388

Press Release: Sanofi's SAR446268 earns US fast track ... Sanofi's SAR446268 earns US fast track designation for the treatment of non-congenital myotonic dystrophy type 1.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06844214

NCT06844214 | A Study to Investigate the Safety, ... The purpose of this study is to evaluate the safety and efficacy of SAR446268 in knocking down dystrophia myotonica protein kinase (DMPK) messenger ribonucleic ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40903903/

Development of an AAV-delivered microRNA gene therapy ... Our data provide evidence of the efficacy and safety of SAR446268. Keywords: AAV; DM1; DMSXL; RNAi; gene therapy; muscular dystrophies ...

4. rheumatologyadvisor.com rheumatologyadvisor.com/news/gene-therapy-fast-tracked-for-non-congenital-myotonic-dystrophy-type-1/

Gene Therapy Fast Tracked for Non-Congenital Myotonic ... The FDA has granted Fast Track designation to SAR446268 for the treatment of non-congenital myotonic dystrophy type 1.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625007245

Development of an AAV-delivered microRNA gene therapy ... Our data provide evidence of the efficacy and safety of SAR446268. ... Outcome Measure for Clinical Trials Efficacy in Myotonic Dystrophy Type 1.

6. musculardystrophynews.com musculardystrophynews.com/news/dm1-gene-therapy-trial-seeks-patients-ages-10-50/

DM1 gene therapy trial seeks patients ages 10-50 SAR446268 is designed to reduce levels of DMPK mRNA in muscle cells. The development and preclinical testing of the therapy were described in ...