A Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping to Evaluate the Safety and Efficacy of ENTR-601-45

Phase 1

Not yet recruiting

• Conditions: Duchenne Muscular Dystrophy (DMD)
• Interventions: Drug: ENTR-601-45; Drug: ENTR-601-45 - matching placebo

• Registration Number: NCT07038824
• Lead Sponsor: Entrada Therapeutics, Inc.

Brief Summary

This is a study of the investigational medicine ENTR-601-45 in participants who have Duchenne muscular dystrophy (DMD), a rare genetic condition. The researchers want to: Test how safe ENTR-601-45 is, learn about any side effects, and look at the potential positive effects of ENTR-601-45, compared to placebo. Placebo looks like the investigational medicine but does not contain any active ingredient. In this summary ENTR-601-45 and placebo are both called study treatments. The study has 2 parts: Part A: to evaluate if ENTR-601-45 is safe and to determine the best dose of ENTR-601-45 for Part B. Part B: to further evaluate the effect and safety of ENTR-601-45 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, muscle biopsies 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-05-01
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-17
• Last Update Submitted: 2025-06-17
• Study First Posted: 2025-06-26
• Last Update Posted: 2025-06-26
• Study Start: 2025-09-30
• Primary Completion: 2029-03-01
• Study Completion: 2029-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 24

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 for a non-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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ENTR-601-45	ENTR-601-45	intravenous infusion every 6 weeks
Placebo	ENTR-601-45 - matching placebo	intravenous infusion every 6 weeks

Primary Outcome Measures

Name	Time	Method
Number of participants with Treatment Emergent Adverse Events (TEAEs) according to study protocol (Part A).	From baseline through End of Study (up to 25 weeks).	Safety will be assessed by monitoring adverse events, physical examination, vital signs and clinical laboratory tests.

Secondary Outcome Measures

Name	Time	Method
Plasma, muscle, and urine concentration of ENTR-601-45 and its final metabolite (Part A)	From baseline through End of Study (Up to 25 weeks).
Change from baseline in dystrophin by Western blot from muscle biopsy at End of Study (Part A)	Baseline, End of Study (Up to 25 weeks)
Change from baseline in dystrophin expression and localization from muscle biopsy at End of Study (Part A)	Baseline, End of Study (Up to 25 weeks)
Percent change from baseline in exon 45 skipping measured in muscle biopsy at End of Study (Part A)	Baseline, End of Study (Up to 25 weeks)
Anti-drug antibody (ADA) and anti-dystrophin antibody in serum (Part A)	From baseline through End of Study (Up to 25 weeks).

Trial Locations

Locations (14)

University Hospital Gent; 🇧🇪 Gent, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

IRCCS Ospedale San Raffaele; 🇮🇹 Milan, Italy

Ospedale Pediatrico Bambino Gesu; 🇮🇹 Rome, Italy

Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore; 🇮🇹 Rome, Italy

Leids Universitair Medisch Centrum; 🇳🇱 Leiden, Netherlands

Stichting Radboud Universitair Medisch Centrum; 🇳🇱 Nijmegen, Netherlands

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Sant Joan de Deu; 🇪🇸 Barcelona, Spain

Leeds General Infirmary; 🇬🇧 Leeds, United Kingdom

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