ENTR-601-45 for Duchenne muscular dystrophy patients amenable to exon 45 skipping

A 2-Part, Randomized, Double-Blind, Placebo-Controlled Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping With an Initial Multiple Ascending Dose Part A to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ENTR-601-45, Followed by Part B to Evaluate the Safety and Efficacy of ENTR-601-45 (ELEVATE-45)

This trial will test whether ENTR-601-45 given by intravenous infusions is safe and helps boys and young men with Duchenne muscular dystrophy who are amenable to exon 45 skipping.

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: 15 sites (Ghent and 14 other locations)
• Trial ID: NCT07038824 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 program uses a two-part design with an initial dose-finding/safety Part A followed by a controlled Part B at the selected dose. Participants receive multiple IV infusions of ENTR-601-45 or matching placebo, with safety, side effects, and signs of benefit compared against placebo in Part B. Those completing the randomized phases may roll into an open-label extension to assess longer-term safety and continued dosing effects. Genetic eligibility is centrally confirmed and prior exon-skipping therapy is excluded.

Who should consider this trial

Good fit: Ideal candidates are males assigned at birth aged 4–20 with genetically confirmed DMD and a dystrophin gene variant amenable to exon 45 skipping, who are ambulatory for Part A and meet other protocol criteria.

Not a fit: Patients who do not have an exon 45–amenable mutation, who previously received exon-skipping therapies, or who have significant comorbidities that prevent protocol adherence are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, ENTR-601-45 could increase production of functional dystrophin and slow muscle degeneration, potentially improving strength and delaying loss of function for eligible patients.

How similar studies have performed: Other exon-skipping oligonucleotide programs have produced modest increases in dystrophin and mixed clinical results, so the approach is promising but not yet definitively proven for clinical benefit.

Eligibility criteria

Inclusion Criteria:

1. Genetic diagnosis of DMD and confirmed pathologic variant in the dystrophin gene amenable to exon 45 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.

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 or current treatment with any exon skipping therapy within the previous 12 months
   2. Prior or current treatment with any gene therapy
   3. Use of anti-coagulants, anti-thrombotics, or anti-platelet agents from 30 days prior to screening and until the end of the study
   4. Use of an immunosuppressant (other than systemic or oral corticosteroid for DMD condition) from 30 days prior to screening until the end of the study.
   5. Treatment with a histone deacetylase (HDAC) inhibitor, including (but not limited to) givinostat from 30 days prior to screening until the end of the study
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 14 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)
• Ospedale Pediatrico Bambino Gesu — Rome, Italy (Recruiting)
• Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore — Rome, Italy (Recruiting)
• Leids Universitair Medisch Centrum — Leiden, Netherlands (Recruiting)
• Stichting Radboud Universitair Medisch Centrum — Nijmegen, Netherlands (Not_yet_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)
• Oxford University Hospitals NHS Foundation Trust — Oxford, United Kingdom (Recruiting)

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