Duchenne Muscular Dystrophy (DMD)
Conditions
Keywords
Duchenne Muscular Dystrophy, DMD, exon skipping therapy, oligonucleotide therapy
Brief summary
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.
Interventions
DRUGENTR-601-44
intravenous infusion
DRUGENTR-601-44 - matching placebo
intravenous infusion
Sponsors
Entrada Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
4 Years to 20 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Treatment Emergent Adverse Events (TEAEs) according to study protocol (Part A and Open Label (OL) Period) | From baseline through End of Study (up to 62 weeks). | Safety will be assessed by monitoring adverse events, physical examination, vital signs and clinical laboratory tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma, muscle, and urine concentration of ENTR-601-44 and its final metabolite (Part A and Open Label (OL) Period) | 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) | 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) | 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) | Baseline, End of Part A (up to 25 weeks) | — |
| Anti-drug antibody (ADA) and anti-dystrophin antibody in serum (Part A and OL Period) | 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) | 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) | 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) | 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) | 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) | Baseline, End of Study (up to 62 weeks) | Ordinal scale with 0 as the minimum score and 34 as the maximum score (higher score - better outcome). |
| Change from baseline to End of OL Period in Performance of the Upper Limb v2.0 (PUL 2.0) (Part A and OL Period) | Baseline, End of Study (up to 62 weeks) | Ordinal scale with 0 as the minimum score and 42 as the maximum score (higher score - better outcome). |
Countries
Belgium, Italy, Spain, United Kingdom
Contacts
STUDY_DIRECTOREntrada Therapeutics Clinical Trials
Entrada Therapeutics, Inc.
Outcome results
None listed