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

• Research type

  Research Study

• Full title

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

• IRAS ID

  1003709

• Contact name

  Jennifer Panagoulias

• Sponsor organisation

  Wave Life Sciences UK Limited

• Eudract number

  2019-004494-56

• Research summary

  This open-label Phase 1b/2a study is being conducted to evaluate the safety, tolerability, PK, PD and clinical effects of WVE-N531 in male paediatric patients with Duchenne muscular dystrophy (DMD). DMD is a fatal, progressive, genetic neuromuscular disease that affects around 1 in 3,500 to 5,000 males born worldwide and is caused by mutations in the gene dystrophin.

  There are currently limited disease-modifying treatment options specifically indicated for patients with DMD who have mutations amenable to exon 53 skipping, none of which have evidence of established clinical benefit, there remains a significant unmet need for patients.

  WVE-N531 is an antisense oligonucleotide (ASO) that is intended for the treatment of DMD in patients with a confirmed mutation in the dystrophin gene that would benefit from exon 53 skipping.

  This is the first clinical study being conducted with WVE-N531. The results of nonclinical studies conducted to date indicate that the primary findings associated with WVE-N531 in mice and monkeys are similar to other ASOs, including some potential for inflammatory and coagulation effects, as well as effects in the liver and kidney. Both coagulation parameters and inflammatory effects are monitorable in the clinical setting via frequent blood sampling and careful clinical observation of patients during and after each infusion. Kidney and liver function will also be monitored through clinical laboratory tests.

  15 patients will be enrolled in the UK and Canada. The study will have 2 parts: Part A and Part B. Part A (3 patients) will involve a dose escalation portion where 4 ascending doses will be given and a multiple dose portion where 3 additional fixed doses will be given. Part B (12 patients) will involve 7 fixed doses.

  Assessments will include blood samples, vitals, physical examinations, functional assessments, questionnaires, echocardiograms, electrocardiograms and muscle biopsies.

• REC name

  South West - Central Bristol Research Ethics Committee

• REC reference

  21/SW/0041

• Date of REC Opinion

  11 Jun 2021

• REC opinion

  Further Information Favourable Opinion