This is a study of the investigational medicine ENTR-601-44 in participants who have Duchenne muscular dystrophy (DMD), a rare genetic condition. The researchers want to: Test how safe ENTR-601-44 is, learn about any side effects, and look at the potential positive effects of ENTR-601-44, compared to placebo. Placebo looks like the investigational medicine but does not contain any active ingredient. In this summary ENTR-601-44 and placebo are both called study treatments. The study has 2 parts: Part A: to evaluate if ENTR-601-44 is safe and to determine the best dose of ENTR-601-44 for Part B. Part B: to further evaluate the effect and safety of ENTR-601-44 at the dose determined in Part A. Participants will be able to roll into an open-label treatment period during which the safety and efficacy of extended dosing will be evaluated. Participants will: * Receive study treatment in the form of multiple intravenous (IV) infusions (slow injection) into a vein over the course of several weeks in Part A and in Part B * Visit the clinic regularly for checkups and tests such as: blood and urine tests, physical examinations, questionnaires, and exercise tests. Participants will have a muscle biopsy at the beginning of their participation and after their last dose to allow researchers to compare whether there have been changes in the muscle as a result of the study drug. Participants are allowed to continue receiving their standard of care therapy for DMD during the study, as long as their health remains stable.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
24
intravenous infusion
intravenous infusion
University Hospital Gent
Ghent, Belgium
RECRUITINGUZ Leuven
Leuven, Belgium
RECRUITINGCentre Hospitalier Régional de la Citadelle
Liège, Belgium
RECRUITINGIRCCS Ospedale San Raffaele
Milan, Italy
NOT_YET_RECRUITINGFondazione Serena Onlus - Centro Clinico NeMO Milano
Milan, Italy
NOT_YET_RECRUITINGOspedale Pediatrico Bambino Gesu
Rome, Italy
NOT_YET_RECRUITINGFondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Rome, Italy
NOT_YET_RECRUITINGHospital Universitario Vall d'Hebron
Barcelona, Spain
RECRUITINGHospital Sant Joan de Deu
Barcelona, Spain
RECRUITINGLeeds General Infirmary
Leeds, United Kingdom
RECRUITING...and 5 more locations
Number of participants with Treatment Emergent Adverse Events (TEAEs) according to study protocol (Part A and Open Label (OL) Period)
Safety will be assessed by monitoring adverse events, physical examination, vital signs and clinical laboratory tests.
Time frame: From baseline through End of Study (up to 62 weeks).
Plasma, muscle, and urine concentration of ENTR-601-44 and its final metabolite (Part A and Open Label (OL) Period)
Time frame: From Baseline through End of Study (up to 62 weeks).
Change from baseline to End of Part A in dystrophin by Western blot from muscle biopsy (Part A)
Time frame: Baseline, End of Part A (up to 25 weeks)
Change from baseline to End of Part A in dystrophin expression and localization from muscle biopsy (Part A)
Time frame: Baseline, End of Part A (up to 25 weeks)
Percent change from baseline to End of Part A in exon 44 skipping measured in muscle biopsy at End of Study (Part A)
Time frame: Baseline, End of Part A (up to 25 weeks)
Anti-drug antibody (ADA) and anti-dystrophin antibody in serum (Part A and OL Period)
Time frame: From baseline through End of Study (up to 62 weeks).
Change from baseline to End of OL Period in 10-Meter Walk/Run (10MWR) (Part A and OL Period)
Time frame: Baseline, End of Study (up to 62 weeks)
Change from baseline to End of OL Period in Timed Rise from Floor (Part A and OL Period)
Time frame: Baseline, End of Study (up to 62 weeks)
Change from baseline to End of OL Period in Timed 4-Stair Climb (4SC) (Part A and OL Period)
Time frame: Baseline, End of Study (up to 62 weeks).
Change from baseline to End of OL Period in 95th centile Stride Velocity (SV95C) (Part A and OL Period)
Time frame: Baseline, End of Study (up to 62 weeks)
Change from baseline to End of OL Period in North Star Ambulatory Assessment (NSAA) (Part A and OL Period)
Ordinal scale with 0 as the minimum score and 34 as the maximum score (higher score - better outcome).
Time frame: Baseline, End of Study (up to 62 weeks)
Change from baseline to End of OL Period in Performance of the Upper Limb v2.0 (PUL 2.0) (Part A and OL Period)
Ordinal scale with 0 as the minimum score and 42 as the maximum score (higher score - better outcome).
Time frame: Baseline, End of Study (up to 62 weeks)
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