SAR446268 gene therapy for non-congenital myotonic dystrophy type 1

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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.

Where it's running

• 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
• Penn Medicine: University of Pennsylvania Health System- Site Number : 8400009
  Philadelphia, Pennsylvania, 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

Study contacts

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

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Quantitative MRI measurement of muscle changes in myotonic dystrophy

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• Portable markerless video system to measure walking in adults with neuromuscular conditions or healthy volunteers.

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• Assessing Readiness and Endpoints for Pediatric Myotonic Dystrophy

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• Once-daily prolonged-release mexiletine for myotonic dystrophy types 1 and 2 (HERCULES)

  This study will test whether once-daily prolonged-release mexiletine can reduce myotonia in people aged 16 and older with genetically confirmed myotonic dystrophy type 1 or 2.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.