Natural History of Duchenne Muscular Dystrophy

A Prospective, Interventional, Baseline Study In Young Male Subjects Aged From 4 to 9 Years

Baseline Study on Duchenne Muscular Dystrophy (DMD) in view to collect data on the natural disease course in a cohort in young male subjects aged from 4 to 9 Years over a period of 6 to 36 months using disease appropriate evaluations.

Study duration from FPFV: Q1 2019 to LPLV: Q4 2026

Primary Ojectives:

• To assess the natural disease course using standardized and disease appropriate evaluations in a cohort of young male subjects aged from 4 to 9 years at inclusion and diagnosed for Duchenne Muscular Dystrophy (DMD).
• To record a baseline period prior to rolling over into a gene therapy phase I/II/III clinical study.

Secondary Objectives:

• To identify clinical, imaging and/or laboratory parameters that could be predictive indicators of the disease course in DMD, within the selected range of age.
• To identify the best outcome measure(s) for further clinical trial assessments.

Inclusion Criteria:

1. Male

2. 4 to 9 years old inclusive

3. Body-weight ≤ 95th percentile or the BMI scale ≤ 95th percentile (according to validated scale in force in country site).

   Related to the DMD disease:

4. Diagnosis of DMD based upon documented gene testing with detailed genotyping

5. Able to achieve at inclusion and screening visits:

   1. NSAA (North Star Ambulatory Assessment) scale > 18 or ≥ 16 if participant is between 4 and < 5 years old at screening and:
   2. Gowers test < or = 7 sec and/or
   3. 6-Minute Walk Test (6MWT): a distance ≥ 350 meters at inclusion visit (M0)

6. Ongoing corticosteroid therapy or initiation of corticosteroid therapy according to standard of care prior to Screening visit

   Related to the study protocol and ICH/GCP (Good Clinical Practice) requirements:

7. Signed informed consent by at least one parent or both parents or legal guardian representative(s), when applicable and according to the country regulation

8. Affiliated to or a beneficiary of a Health Care scheme (according to country regulation)

   Exclusion Criteria:

   Subject will be excluded from enrolment into the study for any of the following reasons:

   Related to the DMD disease severity:

9. Cardiomyopathy based on physical/cardiological examination and echocardiography with Left Ventricular Simpson biplane Ejection Fraction (LVEF) below 55%

10. Respiratory Assistance: need for either a diurnal and/or a nocturnal ventilation

11. Any co-morbidity (ies) and or previous or planned surgical event(s) which may interfere with DMD natural evolution and or evaluation of outcomes designed to assess DMD Natural History

    Related to specific assessments:

12. Muscle testing: inability to cooperate with

13. MRI: metal implants in regions of interest for the study

    Related to the study protocol and ICH/GCP requirements:

14. Unwilling and/or unable to comply with all the study protocol requirements and/or procedures

15. Previous inclusion to another clinical trial with an Investigational Medicinal Product (IMP), within the 3 months or IMP washout period (whichever is longer) prior to the screening visit of the study

16. Previously treated with a gene therapy drug for DMD, such as:

    • any AAV mediated gene transfer products or any gene editing products in a clinical trial or in a clinical setting,
    • if exons skipping drug was used, the last dose of exon skipping drug within 5 half-lives prior to the screening visit

17. Concomitant participation to any other interventional clinical trial