A Study to Investigate the Safety, Tolerability, and Efficacy of SAR446268, an Adeno-associated Viral Vector-mediated Gene Therapy in Participants Aged 10 to 55 Years of Age With Non-congenital Myotonic Dystrophy Type 1 (BrAAVe)

May 29, 2026 updated by: Sanofi

A Phase 1/Phase 2 Open-label Single Arm Study With Dose Escalation (Part A), and Dose Expansion (Part B) Parts to Evaluate the Safety, Tolerability, and Efficacy of SAR446268, an Adeno-associated Viral Vector-mediated Gene Therapy in Participants 10 to 55 Years Old With Non-congenital Myotonic Dystrophy Type 1

This is a Phase 1/Phase 2 open-label single arm, multicenter, and multinational study with SAR446268 for treatment of male and female participants 10 to 55 years old with non-congenital myotonic dystrophy (DM) type 1 (DM1).

The purpose of this study is to evaluate the safety and efficacy of SAR446268 in knocking down dystrophia myotonica protein kinase (DMPK) messenger ribonucleic acid (mRNA) levels and improving neuromuscular function in DM1 participants receiving a single intravenous (IV) administration of SAR446268. The study consists of a dose escalation part (Part A) during which single ascending doses of SAR446268 will be evaluated in 3 distinct cohorts and an optional fourth dose cohort. Once a safe and effective dose is identified, additional participants will be treated in Part B, the dose expansion phase of the study.

The study duration will be 112 weeks (approximately 2 years) for each participant in Parts A and B respectively and includes an optional pre-screening period, approximately 8-week screening phase and a 104-week follow-up period post-SAR446268 administration.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Each participant meeting the eligibility criteria for each of the study parts will receive a single dose administration of SAR446268.

Study Type

Interventional

Enrollment (Estimated)

32

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trial Transparency email recommended (Toll free for US & Canada)
  • Phone Number: option 6 800-633-1610
  • Email: contact-us@sanofi.com

Study Locations

  • Argentina
      • Buenos Aires, Argentina, 1181
        • Recruiting
        • Hospital Italiano de Buenos Aires, Juan Domingo Peron 4190 - Site Number: 0320001
        • Contact:
        • Principal Investigator:
          • Ventura Simonovich
  • Australia
    • Queensland
      • Brisbane, Queensland, Australia, 4029
        • Recruiting
        • Investigational Site Number : 0360001
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Recruiting
        • The Montreal Neurological Institute and Hospital, 3801 rue University - Site Number: 1240001
        • Contact:
        • Principal Investigator:
          • Dr. Erin O'Ferrall
  • Israel
      • Ramat Gan, Israel, 5262100
        • Recruiting
        • Investigational Site Number : 3760002
  • United Kingdom
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Recruiting
        • Investigational Site Number : 8260002
  • United States
    • Florida
      • Gainesville, Florida, United States, 32601
        • Recruiting
        • University of Florida, 2004 Mowry Road - Site Number: 8400005
        • Contact:
        • Principal Investigator:
          • Dr. Subramony
      • Tampa, Florida, United States, 33612
        • Recruiting
        • University of South Florida - Neuromuscular Research, 13330 USF Laurel Drive - Site Number: 8400001
        • Principal Investigator:
          • Dr. Tuan Vu
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center - Neurological Institute, 710 W. 168th, 2nd floor, suite 204 - Site Number : 8400003
        • Contact:
        • Principal Investigator:
          • Dr. Christina Ulane
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Recruiting
        • Virginia Commonwealth University Medical Center- Site Number : 8400006

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

  • For Part A, participants must be 18 to 55 years of age inclusive, at the time of signing the informed consent.

  • For Part B, participants must be as follows:

    • 10 to 17 years of age inclusive, at the time of signing the informed consent or,
    • 18 to 55 years of age inclusive, at the time of signing the informed consent.
  • Participants with non-congenital onset DM1
  • Participants presenting with signs of DM1 including myotonia and muscle weakness, as diagnosed previously by a clinician based on medical history.
  • Participants with genetic diagnosis of DM1 [cytosine-thymine-guanine (CTG) repeat length ≥50 in one allele from medical history]
  • Participants who can walk independently for at least 10 meters at screening (orthoses and ankle braces allowed).

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  • Participants with neutralizing antibodies against the AAV.SAN011 capsid
  • Participants with left ventricular ejection fraction <50%

  • Participants with liver or biliary disease defined as having at least one of the following:

    • ALT >3 x ULN and AST >3 x ULN
    • Alkaline phosphatase >3 x ULN
    • Total bilirubin >1.5 x ULN (unless has a genetically confirmed diagnosis of Gilbert's syndrome)
    • Direct bilirubin ≥1.5 x ULN
    • Participants with International normalized ratio >1.5

  • Participants with renal disease defined as:

    • Serum creatinine >1.5 x ULN and/or estimated glomerular filtration rate <60 mL/min/1.73 m2 as determined by Chronic Kidney Disease Epidemiology Collaboration (2021) for those age ≥18 years and Bedside Schwartz Equation for those <18 years

  • Participants with chronic respiratory insufficiency and on long term/hull-time ventilatory assistance requiring at least 6 hours per day for at least 21 consecutive days.
  • Participants with contraindication to corticosteroid or with conditions that could worsen in the presence of corticosteroids, as determined by the Investigator.
  • Participants with active hepatitis B or C infection; HBsAg (+), or HCV RNA (+), or current antiviral therapy for either.
  • Participants with HBcAb (+) who are not amenable for prophylactic anti-HBV therapy or pre-emptive therapy guided by serial HBV DNA monitoring during the corticosteroids therapy.
  • Participants at high risk for tuberculosis reactivation during the corticosteroids therapy as determined by the Investigator.
  • Participants with a known HIV infection
  • Participants with serious intercurrent illness that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival.
  • Participants with recent history of or current drug or alcohol abuse in the past 12 months prior to screening.
  • Participants with history of tibialis anterior biopsy within 12 weeks from Day 1 or planning to undergo tibialis anterior biopsies during the duration of this clinical trial.
  • Participants with significant developmental delay, intellectual disability, or behavioral neuropsychiatric manifestations as determined by the Investigator.
  • Participants with previous systemic corticosteroids treatment at doses of >5 mg/day within 15 days of Day 1
  • Participants with previous treatment with anti-myotonic medication within 15 days of Day 1
  • Participants not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
  • Participants who have been classified as severe cardiac risk by the Investigator.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SAR446268
Participants will receive a single dose of SAR446268 on Day 1
Biological: SAR446268
Pharmaceutical form: Solution for infusion; Route of administration: IV infusion
Other Names:
  • SAR466268

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A and Part B: Incidence of treatment-emergent adverse events (TEAEs) following SAR446268 administration
Time Frame: Baseline to Week 52
Number of TEAEs post-SAR446268 administration
Baseline to Week 52
Part B: Proportion of participants with at least 40% DMPK mRNA knockdown in muscle biopsy at Weeks 12 and 52 following SAR446268 administration
Time Frame: Weeks 12 and 52
Weeks 12 and 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Change in 10-meter walk-run test from baseline to Weeks 26 and 52 following SAR446268 administration
Time Frame: Baseline to Week 26 and 52
The 10-meter walk-run test is a mobility test that measures how fast a participant can traverse 10 meters with or without assisted devices.
Baseline to Week 26 and 52
Part A: Change in myotonia from baseline to Weeks 26 and 52 following SAR446268 administration as measured by the hand opening time (middle finger)
Time Frame: Baseline to Week 26 and 52
This test for myotonia measures how quickly a participant can open his/her hand after making a tight fist.
Baseline to Week 26 and 52
Part A: Change in bilateral hand grip test from baseline to Weeks 26 and 52 following SAR446268 administration
Time Frame: Baseline to Week 26 and 52
This test for strength of the hand muscles measures the maximum force generated by a participant's hand grip using a dynamometer.
Baseline to Week 26 and 52
Part A: Proportion of participants with at least 40% DMPK mRNA knockdown in muscle biopsy at Weeks 12 and 52 following SAR446268 administration
Time Frame: Weeks 12 and 52
Weeks 12 and 52
Part A: Change in DMPK mRNA levels in muscle biopsy from baseline to Weeks 12 and 52 following SAR446268 administration
Time Frame: Baseline to Week 12 and 52
Baseline to Week 12 and 52
Part A: Change in RNA splicing index in muscle biopsy from baseline to Weeks 12 and 52 following SAR446268 administration
Time Frame: Baseline to Week 12 and 52
Baseline to Week 12 and 52
Part A: Assessment of the duration of AAV vector shedding of SAR446268 in sampling of urine, saliva, and semen at 4-week intervals following SAR446268 administration
Time Frame: Baseline, Weeks 4, 8, and 12
Baseline, Weeks 4, 8, and 12
Part B: Change in 10-meter walk-run test from baseline to Weeks 26 and 52 following SAR446268 administration
Time Frame: Baseline to Week 26 and 52
The 10-meter walk-run test is a mobility test that measures how fast a participant can traverse 10 meters with or without assisted devices.
Baseline to Week 26 and 52
Part B: Change in myotonia from baseline to Weeks 26 and 52 following SAR446268 administration as measured by the hand opening time (middle finger)
Time Frame: Baseline to Week 26 and 52
This test for myotonia measures how quickly a participant can open his/her hand after making a tight fist.
Baseline to Week 26 and 52
Part B: Change in bilateral hand grip test from baseline to Weeks 26 and 52 following SAR446268 administration
Time Frame: Baseline to Week 26 and 52
This test for strength of the hand muscles measures the maximum force generated by a participant's hand grip using a dynamometer.
Baseline to Week 26 and 52
Part B: Change in DMPK mRNA knockdown in muscle biopsy from baseline to Weeks 12 and 52 following SAR446268 administration
Time Frame: Baseline to Week 12 and 52
Baseline to Week 12 and 52
Part B: Change in RNA splicing index in muscle biopsy from baseline to Weeks 12 and 52 following SAR446268 administration
Time Frame: Baseline to Week 12 and 52
Baseline to Week 12 and 52
Part B: Assessment of the duration of AAV shedding of SAR446268 in sampling of urine, saliva, and semen at 4-week intervals following SAR446268 administration
Time Frame: Baseline, Weeks 4, 8, and 12
Baseline, Weeks 4, 8, and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2025

Primary Completion (Estimated)

February 28, 2029

Study Completion (Estimated)

April 27, 2032

Study Registration Dates

First Submitted

February 19, 2025

First Submitted That Met QC Criteria

February 19, 2025

First Posted (Actual)

February 25, 2025

Study Record Updates

Last Update Posted (Actual)

June 1, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DFI17808
  • U1111-1290-9594 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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