RecruitingPhase 1Phase 2NCT04906460

Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy (FORWARD-53)

An Open-label Phase 1b/2 Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy


Sponsor

Wave Life Sciences Ltd.

Enrollment

26 participants

Start Date

Sep 28, 2021

Study Type

INTERVENTIONAL

Conditions

Summary

This is a Phase 1b/2 open-label study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical effects of intravenous (IV) WVE-N531 in patients with Duchenne muscular dystrophy (DMD). To participate in the study, patients must have a documented mutation of the DMD gene that is amenable to exon 53 skipping intervention. This study has 3 parts, Part A, Part B, including Part B Extension Arm, and Part C. Part A is completed. Part B is completed. Following completion of Part B, all patients elected to continue to receive study drug in the optional Part B open-label Extension Arm. Part C has been added to the study and will enroll new patients.


Eligibility

Sex: MALEMin Age: 4 YearsMax Age: 18 Years

Inclusion Criteria20

  • Part A and Part B:
  • Part A patients may be screened for Part B upon completion of a washout period of ≥18 weeks from last dose in Part A. New patients may also be screened for Part B
  • Diagnosis of DMD based on clinical phenotype.
  • Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
  • Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) (Part B ).
  • Ambulatory or non-ambulatory male
  • Stable pulmonary and cardiac function, as measured by the following: (Part B):
  • \. Reproducible percent predicted forced vital capacity (FVC) ≥50%; 2. Left ventricular ejection fraction (LVEF) >55% in patients <10 years of age and >45% in patients ≥10 years of age, as measured (and documented) by echocardiogram (ECHO) and/or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.
  • Adequate muscle at Screening to perform open muscle biopsies, preferably deltoid.
  • \. Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy that occurred ≥6 months prior to Screening and no changes in dose ≤3 months prior to Screening visit (Part B ).
  • Part C
  • New patients to be screened for Part C.
  • Diagnosis of DMD based on clinical phenotype.
  • Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
  • Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) .
  • Ambulatory male
  • Stable pulmonary and cardiac function, as measured by the following:
  • \. Reproducible percent predicted forced vital capacity (FVC) ≥50%; 2. Left ventricular ejection fraction (LVEF) >55% in patients as measured (and documented) by echocardiogram (ECHO) and/or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.
  • \. Adequate muscle at Screening to perform open muscle biopsies, preferably deltoid.
  • \. Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy that occurred ≥6 months prior to Screening and no changes in dose ≤3 months prior to Screening visit .

Exclusion Criteria4

  • Clinically significant medical finding on the physical examination other than DMD that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the study procedures.
  • Part B and Part C: Major surgery within 3 months prior to Day 1 or planned major surgery for any time during the study.
  • Part B: Diagnosis of active alcohol, cannabinoid, or other substance use disorder (except nicotine) within 6 months prior to the Screening visit
  • Part C: Any recreational substance use (including prescribed cannabinoids), with the exception of nicotine, irrespective of legality, within 2 months prior to Screening and/or unwilling to refrain from such use for the duration of the study.

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Interventions

DRUGWVE-N531

WVE-N531 is an antisense oligonucleotide (ASO)


Locations(5)

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Rare Disease Research LLC

Atlanta, Georgia, United States

Istiklal Hospital/ Clinical Research Unit

Amman, Jordan

The Specialty Hospital (TSH)/ Advanced Clinical Center

Amman, Jordan

Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust

Headington, Oxford, United Kingdom

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NCT04906460


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