SAR446268 gene therapy for non-congenital myotonic dystrophy type 1

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 will try a single intravenous dose of SAR446268 gene therapy to lower toxic DMPK mRNA and improve muscle function in people aged 10 to 55 with non‑congenital myotonic dystrophy type 1.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 10 Years to 55 Years
• Sex: All
• Sponsor: Sanofi (industry)
• Locations: 9 sites (Gainesville, Florida and 8 other locations)
• Trial ID: NCT06844214 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm, multicenter Phase 1/2 study gives a single IV dose of SAR446268 to participants with non‑congenital DM1 to test safety, tolerability, DMPK mRNA knockdown, and neuromuscular outcomes. Part A uses a dose‑escalation design with three (and an optional fourth) ascending-dose cohorts to identify a safe and active dose, and Part B is a dose-expansion phase treating additional participants at the selected dose. Each participant receives one administration and is followed for approximately 112 weeks with scheduled clinical, laboratory, and functional assessments. The trial enrolls males and females aged 10–55 who can walk at least 10 meters and have genetically confirmed non‑congenital DM1.

Who should consider this trial

Good fit: Ideal candidates are people aged 10–55 with genetically confirmed non‑congenital DM1 (CTG repeat ≥50) who can walk independently for at least 10 meters.

Not a fit: Patients with congenital-onset DM1, CTG repeat counts below 50, those unable to walk independently, or individuals with contraindications to AAV-based gene therapy may not receive benefit from this intervention.

Why it matters

Potential benefit: If successful, the treatment could lower toxic DMPK mRNA and produce measurable improvements in muscle strength, myotonia, and functional ability.

How similar studies have performed: Related gene-silencing and gene‑therapy approaches have shown promise in preclinical models and some early-phase neuromuscular studies, but AAV-mediated DMPK knockdown in humans is largely novel.

Eligibility criteria

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 \>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.
* 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.

Where this trial is running

Gainesville, Florida and 8 other locations

• University of Florida, 2004 Mowry Road - Site Number: 8400005 — Gainesville, Florida, United States (RECRUITING)
• University of South Florida - Neuromuscular Research, 13330 USF Laurel Drive - Site Number: 8400001 — Tampa, Florida, United States (RECRUITING)
• Columbia University Medical Center - Neurological Institute, 710 W. 168th, 2nd floor, suite 204 - Site Number : 8400003 — New York, New York, United States (RECRUITING)
• Virginia Commonwealth University Medical Center- Site Number : 8400006 — Richmond, Virginia, United States (RECRUITING)
• Hospital Italiano de Buenos Aires, Juan Domingo Peron 4190 - Site Number: 0320001 — Buenos Aires, Argentina (RECRUITING)
• Investigational Site Number : 0360001 — Brisbane, Queensland, Australia (RECRUITING)
• The Montreal Neurological Institute and Hospital, 3801 rue University - Site Number: 1240001 — Montreal, Quebec, Canada (RECRUITING)
• Investigational Site Number : 3760002 — Ramat Gan, Israel (RECRUITING)
• Investigational Site Number : 8260002 — Newcastle upon Tyne, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Trial Transparency email recommended (Toll free for US & Canada)

Conditions: Myotonic Dystrophy