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 50 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 4th 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 110 weeks (approximately 2 years) for each participant in Parts A and B respectively and includes a 6-week screening phase and a 104-week follow-up period post-SAR446268 administration.
Each participant meeting the eligibility criteria for each of the study parts will receive a single dose administration of SAR446268.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Pharmaceutical form: Solution for infusion; Route of administration: IV infusion
University of Florida, 2004 Mowry Road - Site Number: 8400005
Gainesville, Florida, United States
RECRUITINGUniversity of South Florida - Neuromuscular Research, 13330 USF Laurel Drive - Site Number: 8400001
Tampa, Florida, United States
RECRUITINGColumbia University Medical Center - Neurological Institute, 710 W. 168th, 2nd floor, suite 204 - Site Number : 8400003
New York, New York, United States
RECRUITINGHospital Italiano de Buenos Aires, Juan Domingo Peron 4190 - Site Number: 0320001
Buenos Aires, Argentina
RECRUITINGInvestigational Site Number : 0360001
Brisbane, Queensland, Australia
RECRUITINGThe Montreal Neurological Institute and Hospital, 3801 rue University - Site Number: 1240001
Montreal, Quebec, Canada
RECRUITINGInvestigational Site Number : 3760002
Ramat Gan, Israel
RECRUITINGInvestigational Site Number : 8260002
Newcastle upon Tyne, United Kingdom
RECRUITINGPart A and Part B: Incidence of treatment-emergent adverse events (TEAEs) following SAR446268 administration
Number of TEAEs post-SAR446268 administration
Time frame: 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
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.
Time frame: 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)
This test for myotonia measures how quickly a participant can open his/her hand after making a tight fist.
Time frame: Baseline to Week 26 and 52
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.
Time frame: 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
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
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
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
Part B: 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.
Time frame: 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)
This test for myotonia measures how quickly a participant can open his/her hand after making a tight fist.
Time frame: Baseline to Week 26 and 52
Part B: 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.
Time frame: 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
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
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
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