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

NCT06844214 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: DFI17808U1111-1290-9594
• Study Type: interventional
• Target: 32
• Locations: 6 countries
• Sites: 9

Brief Summary

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.

Conditions

Myotonic Dystrophy

Outcome Measures

Primary Outcomes (2)

• Part A and Part B: Incidence of treatment-emergent adverse events (TEAEs) following SAR446268 administration

  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

  Weeks 12 and 52

Secondary Outcomes (13)

• Part A: Change in 10-meter walk-run test from baseline to Weeks 26 and 52 following SAR446268 administration

  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)

  Baseline to Week 26 and 52

• Part A: Change in bilateral hand grip test from baseline to Weeks 26 and 52 following SAR446268 administration

  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

  Weeks 12 and 52

• Part A: Change in DMPK mRNA levels in muscle biopsy from baseline to Weeks 12 and 52 following SAR446268 administration

  Baseline to Week 12 and 52

Study Arms (1)

SAR446268

EXPERIMENTAL

Participants will receive a single dose of SAR446268 on Day 1

Biological: SAR446268

Interventions

SAR446268 BIOLOGICAL

Pharmaceutical form: Solution for infusion; Route of administration: IV infusion

SAR446268

Eligibility Criteria

• Age: 10 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• to 17 years of age inclusive, at the time of signing the informed consent or,
• 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).

You may not qualify if:

• 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 \>2 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (9)

University of Florida, 2004 Mowry Road - Site Number: 8400005

Gainesville, Florida, 32601, United States

RECRUITING

University of South Florida - Neuromuscular Research, 13330 USF Laurel Drive - Site Number: 8400001

Tampa, Florida, 33612, United States

RECRUITING

Columbia University Medical Center - Neurological Institute, 710 W. 168th, 2nd floor, suite 204 - Site Number : 8400003

New York, New York, 10032, United States

RECRUITING

Virginia Commonwealth University Medical Center- Site Number : 8400006

Richmond, Virginia, 23219, United States

RECRUITING

Hospital Italiano de Buenos Aires, Juan Domingo Peron 4190 - Site Number: 0320001

Buenos Aires, 1181, Argentina

RECRUITING

Investigational Site Number : 0360001

Brisbane, Queensland, 4029, Australia

RECRUITING

The Montreal Neurological Institute and Hospital, 3801 rue University - Site Number: 1240001

Montreal, Quebec, H3A 2B4, Canada

RECRUITING

Investigational Site Number : 3760002

Ramat Gan, 5262100, Israel

RECRUITING

Investigational Site Number : 8260002

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Related Links

• DFI17808 Plain Language Results Summary

MeSH Terms

Conditions

Myotonic Dystrophy

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Trial Transparency email recommended (Toll free for US & Canada)

CONTACT

800-633-1610; contact-us@sanofi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: February 25, 2025
• Study Start: July 23, 2025
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): April 27, 2032
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AR (1); IL (1); GB (1); US (4); AU (1); CA (1)