ENTR-601-44 treatment for Duchenne muscular dystrophy eligible for exon 44 skipping

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)

This trial will test whether intravenous ENTR-601-44 is safe and helps boys and young men with Duchenne muscular dystrophy whose genetics make them eligible for exon 44 skipping, compared with a placebo.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 4 Years to 20 Years
• Sex: Male
• Sponsor: Entrada Therapeutics, Inc. (Industry-sponsored)
• Locations: 14 sites (Ghent and 13 other locations)
• Trial ID: NCT07037862 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 interventional study enrolls males assigned at birth aged 4–20 with genetically confirmed DMD amenable to exon 44 skipping. Part A is a double-blind, dose-finding period comparing ENTR-601-44 to a matching placebo with an open-label extension for longer-term safety and dosing; Part B further studies safety and effects at the selected dose. Participants receive multiple IV doses, undergo muscle biopsy and regular safety and functional assessments, and are monitored for side effects and potential increases in dystrophin or functional change. The goal is to identify a tolerable dosing regimen and look for signs of clinical or biomarker benefit versus placebo.

Who should consider this trial

Good fit: Boys or young men assigned male at birth, aged 4–20, with a genetic diagnosis of DMD confirmed to be amenable to exon 44 skipping, who are ambulatory at screening and able to undergo muscle biopsy and study visits are ideal candidates.

Not a fit: People who are not genetically eligible for exon 44 skipping, are female, are non-ambulatory, or have other significant medical conditions that interfere with protocol requirements may not receive benefit from this approach.

Why it matters

Potential benefit: If successful, ENTR-601-44 could increase production of functional dystrophin in patients amenable to exon 44 skipping and potentially slow disease progression.

How similar studies have performed: Other exon-skipping antisense oligonucleotide therapies targeting different DMD exons have produced modest dystrophin increases with mixed clinical benefit, so the overall approach has partial precedent but exon-specific outcomes remain uncertain.

Eligibility criteria

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.

Where this trial is running

Ghent and 13 other locations

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

Conditions Duchenne Muscular Dystrophy; DMD; exon skipping therapy; oligonucleotide therapy