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.
For Part A, participants must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
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 with neutralizing antibodies against the AAV.SAN011 capsid
Participants with left ventricular ejection fraction <50%
ALT >3 x ULN and AST >3 x ULN
Alkaline phosphatase >3 x ULN
Single group
SAR446268
Biological/VaccinePharmaceutical form: Solution for infusion; Route of administration: IV infusion
Part A and Part B: Incidence of treatment-emergent adverse events (TEAEs) following SAR446268 administration
Number of TEAEs post-SAR446268 administration
Part B: Proportion of participants with at least 40% DMPK mRNA knockdown in muscle biopsy at Weeks 12 and 52 following SAR446268 administration
Part A: Change in 10-meter walk-run test from baseline to Weeks 26 and 52 following SAR446268 administration
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.
Part A: Change in myotonia from baseline to Weeks 26 and 52 following SAR446268 administration as measured by the hand opening time (middle finger)
This test for myotonia measures how quickly a participant can open his/her hand after making a tight fist.
Part A: Change in bilateral hand grip test from baseline to Weeks 26 and 52 following SAR446268 administration
This test for strength of the hand muscles measures the maximum force generated by a participant's hand grip using a dynamometer.
Part A: Proportion of participants with at least 40% DMPK mRNA knockdown in muscle biopsy at Weeks 12 and 52 following SAR446268 administration
