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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

A Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping to Evaluate the Safety and Efficacy of ENTR-601-44

A 2-Part, Randomized, Double-Blind, Placebo-Controlled Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping With an Initial Multiple Ascending Dose Part A to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ENTR-601-44, Followed by Part B to Evaluate the Safety and Efficacy of ENTR-601-44 (ELEVATE-44)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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 * A Double-Blind Period, to evaluate if ENTR-601-44 is safe and to determine the best dose of ENTR-601-44 for Part B. * Following the Double-Blind period, participants will roll into an open-label treatment period during which the safety and efficacy of extended dosing will be evaluated. * Part B * To further evaluate the effect and safety of ENTR-601-44 at the dose determined in Part A. 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.

Who May Be Eligible (Plain English)

Principal inclusion criteria 1. Genetic diagnosis of Duchenne muscular dystrophy (DMD) and confirmed pathologic variant in the dystrophin gene amenable to exon 44 skipping as reviewed by a central genetic counselor. 2. Assigned male at birth with clinical signs compatible with Duchenne muscular dystrophy as determined by the investigator. 3. Part A: 4-20 years of age, inclusive. 4. Ambulatory Status Part A: ambulatory with a Performance of the Upper Limb v2.0 (PUL 2.0) Entry as per protocol at Screening 5. Adequate muscle for obtaining tissue biopsy as assessed by the investigator. 6. Other protocol-defined criteria apply. Principal exclusion criteria 1. Any significant concomitant medical condition that might interfere with the ability to comply with protocol requirements. 2. Has an acute illness within 4 weeks prior to the first dose of study drug which may interfere with study measurements or jeopardize participant's safety. 3. Use of the following medications: 1. Prior treatment with any exon skipping therapy at any time 2. Prior treatment with any gene therapy at any time 3. Use of anti-coagulants, anti-thrombotics, or anti-platelet agents 4. Use of an immunosuppressants (other than oral corticosteroids for DMD conditions) 5. Has taken or is currently taking a histone deacetylase (HDAC) inhibitor, including (but not limited to) givinostat 4. Laboratory abnormalities. 5. Daytime ventilator dependence or any use of invasive mechanical ventilation via tracheostomy. 6. Has an abnormal electrocardiogram (ECG) reading assessed as clinically significant by the investigator, and/or a QT interval with Fridericia correction method (QTcF) \>450 msec at Screening or prior to the first dose of study drug on Day 1. 7. Received any experimental or investigational drug, etc. within 3 months prior to first dose or within 5 half-lives (whichever is longer). 8. Other protocol-defined criteria apply. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Principal inclusion criteria 1. Genetic diagnosis of Duchenne muscular dystrophy (DMD) and confirmed pathologic variant in the dystrophin gene amenable to exon 44 skipping as reviewed by a central genetic counselor. 2. Assigned male at birth with clinical signs compatible with Duchenne muscular dystrophy as determined by the investigator. 3. Part A: 4-20 years of age, inclusive. 4. Ambulatory Status Part A: ambulatory with a Performance of the Upper Limb v2.0 (PUL 2.0) Entry as per protocol at Screening 5. Adequate muscle for obtaining tissue biopsy as assessed by the investigator. 6. Other protocol-defined criteria apply. Principal exclusion criteria 1. Any significant concomitant medical condition that might interfere with the ability to comply with protocol requirements. 2. Has an acute illness within 4 weeks prior to the first dose of study drug which may interfere with study measurements or jeopardize participant's safety. 3. Use of the following medications: 1. Prior treatment with any exon skipping therapy at any time 2. Prior treatment with any gene therapy at any time 3. Use of anti-coagulants, anti-thrombotics, or anti-platelet agents 4. Use of an immunosuppressants (other than oral corticosteroids for DMD conditions) 5. Has taken or is currently taking a histone deacetylase (HDAC) inhibitor, including (but not limited to) givinostat 4. Laboratory abnormalities. 5. Daytime ventilator dependence or any use of invasive mechanical ventilation via tracheostomy. 6. Has an abnormal electrocardiogram (ECG) reading assessed as clinically significant by the investigator, and/or a QT interval with Fridericia correction method (QTcF) \>450 msec at Screening or prior to the first dose of study drug on Day 1. 7. Received any experimental or investigational drug, etc. within 3 months prior to first dose or within 5 half-lives (whichever is longer). 8. Other protocol-defined criteria apply.

Treatments Being Tested

DRUG

ENTR-601-44

intravenous infusion

DRUG

ENTR-601-44 - matching placebo

intravenous infusion

Locations (14)

University Hospital Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
Centre Hospitalier Régional de la Citadelle
Liège, Belgium
IRCCS Ospedale San Raffaele
Milan, Italy
Fondazione Serena Onlus - Centro Clinico NeMO Milano
Milan, Italy
Ospedale Pediatrico Bambino Gesu
Rome, Italy
Hospital Universitario Vall d'Hebron
Barcelona, Spain
Hospital Sant Joan de Deu
Barcelona, Spain
Leeds General Infirmary
Leeds, United Kingdom
Alder Hey Children's NHS Foundation Trust
Liverpool, United Kingdom
Great Ormond Street Hospital for Children
London, United Kingdom
Royal Manchester Children's Hospital
Manchester, United Kingdom
Freeman Hospital
Newcastle upon Tyne, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom