Long-Term Extension Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon Skipping to Evaluate the Safety and Efficacy of Endosomal Escape Vehicle Phosphorodiamidate Morpholino Oligomer Platform Products (ELEVATE-LTE)

Official title

A Phase 2, Open-Label Long-Term Extension Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon Skipping to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Efficacy of Endosomal Escape Vehicle Phosphorodiamidate Morpholino Oligomer Platform Products (ELEVATE-LTE)

Overview

This is a study of investigational medicines ENTR-601-44 and ENTR-601-45 designed to evaluate the long-term safety and tolerability of study drugs in participants with Duchenne muscular dystrophy (DMD). The investigational medicines are currently being investigated in multiple ascending dose parent studies. After participants complete their respective parent study, there is a need to understand the effects of long-term administration of ENTR-601-44 and ENTR-601-45. Participants enrolling in this study will begin this long-term extension (LTE) study at the dose level they received upon completion of the parent study with possible dose escalation in the LTE study based on emerging safety and efficacy data from the parent studies. Participants will: * Receive study treatment in the form of multiple intravenous (IV) infusions (slow injections) into a vein over the course of several weeks * Visit the clinic regularly for checkups and tests such as: blood and urine tests, physical examinations, questionnaires, and excersice 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 results 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

• Drug ENTR-601-44
  ENTR-601-44 intravenous infusion
• Drug ENTR-601-45
  ENTR-601-45 intravenous infusion

Primary outcome measures

• Number of participants with Treatment Emergent Adverse Events (TEAEs) according to study protocol (Part A and OL Period) [Time frame: From baseline through End of Study (up to 2 years).]

Secondary outcome measures (8)

• Plasma concentration of study drug compounds and their final metabolite [Time frame: From baseline through End of Study (up to 2 years).]
• Change from parent study Part A and OL Period baselines to LTE EOS in 10-Meter Walk/Run (10MWR) [Time frame: From baseline through End of Study (up to 2 years).]
• Change from parent study Part A and OL Period baselines to LTE EOS in timed rise from floor (TRF) [Time frame: From baseline through End of Study (up to 2 years).]
• Change from parent study Part A and OL Period baselines to LTE EOS in Timed 4-Stair Climb (4SC) [Time frame: From baseline through End of Study (up to 2 years).]
• Change from parent study Part A and OL Period baselines to LTE EOS in stride velocity 95th centile (SV95C) [Time frame: From baseline through End of Study (up to 2 years).]
• Change from parent study Part A and OL Period baselines to LTE EOS in North Star Ambulatory Assessment (NSAA) [Time frame: From baseline through End of Study (up to 2 years).]
• Change from parent study Part A and OL Period baselines to LTE EOS in Performance of the Upper Limb v2.0 (PUL 2.0) [Time frame: From baseline through End of Study (up to 2 years).]
• Anti-drug antibody (ADA) and anti-dystrophin antibody in serum [Time frame: From baseline through End of Study (up to 2 years).]

Eligibility criteria

Inclusion criteria

• Willing and able to provide consent (if at age of majority) or assent (if a minor)
• Participant completed clinical study ENTR-601-44-201 or ENTR-601-45-201
• Males who are sexually active with a female partner of childbearing potential must agree to use condoms during sexual intercourse

Exclusion criteria

• Any change from the applicable parent study eligibility criteria, including safety events during the parent study, that in the opinion of the investigator in consultation with the medical monitor and/or sponsor designee precludes safe use of study drug
• Participant has a condition or circumstance that in the view of the investigator places the subject at high risk of poor treatment compliance or for not completing the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 6 centers

• Leeds General Infirmary — Leeds
• Alder Hey Children's NHS Foundation Trust — Liverpool
• Great Ormond Street Hospital for Children — London
• Royal Manchester Children's Hospital — Manchester
• Freeman Hospital — Newcastle upon Tyne
• Oxford University Hospitals NHS Foundation Trust — Oxford

Italy · 4 centers

• IRCCS Ospedale San Raffaele — Milan
• Fondazione Serena Onlus - Centro Clinico NeMO Milano — Milan
• Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuo — Roma
• Ospedale Pediatrico Bambino Gesu — Rome

Belgium · 3 centers

• University Hospital Gent — Ghent
• UZ Leuven — Leuven
• Centre Hospitalier Régional de la Citadelle — Liège

Netherlands · 2 centers

• Leids Universitair Medisch Centrum — Leiden
• Stichting Radboud Universitair Medisch Centrum — Nijmegen

Spain · 2 centers

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Sant Joan de Deu — Barcelona

Identifiers

NCT: NCT07682129 · ENTR-601-DMD-202 · 2025-525124-10-00 · U1111-1334-9287

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗