A 2-Part, Randomized, Double-Blind, Placebo-Controlled Study in Participants with Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping to Evaluate the Safety and Efficacy of ENTR-601-44 (ELEVATE-44)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Entrada Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

16 May 2025 → ongoing

Decision date (initial)

2025-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Entrada Therapeutics, Inc.

External identifiers

EU CT number

2024-517584-23-00

WHO UTN

U1111-1316-5469

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Safety, Dose response

Part A and OL Period: To evaluate the safety and tolerability of ENTR-601-44 in participants with Duchenne muscular dystrophy (DMD)

Secondary objectives 4

1. To characterize the pharmacokinetics of ENTR-601-44 in participants with DMD in Part A
2. To characterize the pharmacodynamics of ENTR-601-44 in participants with DMD in Part A
3. To evaluate the immune response to ENTR-601-44 in participants with DMD in Part A
4. To evaluate the impact of ENTR-601-44 on measures of function in participants with DMD after extended dosing (Part A and OL Period)

Conditions and MedDRA coding

Duchenne Muscular Dystrophy

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Federal Institute For Drugs And Medical Devices, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Genetic diagnosis of 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

Exclusion criteria 8

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: a. Prior treatment with any exon skipping therapy at any time b. Prior treatment with any gene therapy at any time From at least 30 days prior to the start of the screening period until the end of the study: c. Use of anti-coagulants, anti-thrombotics, or anti-platelet agents d. Use of immunosuppressants (other than oral corticosteroids for DMD conditions) e. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence and severity of treatment emergent adverse events (TEAEs) (Part A and OL Period))
2. Changes in vital sign measurements (Part A and OL Period)
3. Changes in clinical laboratory results (Part A and OL Period)
4. Changes in electrocardiogram (ECG) parameters (Part A and OL Period)
5. Changes in physical examination findings (Part A and OL Period)

Secondary endpoints 11

1. Plasma, muscle, and urine concentration of ENTR-601-44 and its final metabolite (Part A and OL Period)
2. Change from baseline in dystrophin by Western blot from muscle biopsy (Part A)
3. Change from baseline to End of Part A in dystrophin expression and localization from muscle biopsy (Part A)
4. Percent change from baseline to End of Part A in exon 44 skipping measured in muscle biopsy (Part A)
5. Anti-drug antibody (ADA) and anti-dystrophin antibody in serum (Part A and OL Period))
6. Change from baseline to End of OL Period in 10-Meter Walk/Run (10MWR) (Part A and OL Period)
7. Change from baseline to End of OL Period in Timed Rise from Floor (Part A and OL Period)
8. Change from baseline to End of OL Period in Timed 4-Stair Climb (4SC) (Part A and OL Period)
9. Change from baseline to End of OL Period in 95th centile Stride Velocity (SV95C) (Part A and OL Period)
10. Change from baseline to End of OL Period in North Star Ambulatory Assessment (NSAA) (Part A and OL Period)
11. Change from baseline to End of OL Period in Performance of the Upper Limb v2.0 (PUL 2.0) (Part A and OL Period)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Entrada Therapeutics Inc.

Sponsor organisation

Entrada Therapeutics Inc.

Address

1 Design Center Place Suite 17-500

City

Boston

Postcode

02210-2349

Country

United States

Scientific contact point

Organisation

Entrada Therapeutics Inc.

Contact name

Regulatory Affairs

Public contact point

Organisation

Entrada Therapeutics Inc.

Contact name

Regulatory Affairs

Third parties 10

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 87 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications