Duchenne muscular dystrophy MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: WVE-210201
Product Code: WVE-210201
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: WVE-210201
CAS Number:
Sponsors
Wave Life Sciences UK Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Patient and/or parent or legal guardian must have the ability and be willing to provide written informed consent prior to any study-related procedures. 2. Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase. 3. Documented mutation in the Dystrophin gene associated with DMD that is amenable to exon 51 skipping. 4. Ambulatory male, able to walk independently for at least 10 meters in 20 seconds or less at the time of Screening visit 5. Age of =5 and =12 years at time of randomization 6. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures, including undergoing the biopsy procedures. 7. Stable pulmonary and cardiac function, as measured by: a. Reproducible percent predicted forced vital capacity (FVC) =50% b. Left ventricular ejection fraction (LVEF) >55% in patients 45% in patients =10 years of age, as measured (and documented) by echocardiogram. 8. Currently on a stable corticosteroid therapy regimen, defined as: initiation of systemic corticosteroid therapy occurred =6 months prior to Screening, and no changes in dose =3 months prior to Screening visit. 9. Adequate deltoid muscle at baseline to perform open muscle biopsies 10. Sexually mature males must be willing to use contraception for the duration of the study, if the patient is sexually active. 11. Patient and caregivers must agree not to post any study-related information on social media. Are the trial subjects under 18? yes Number of subjects for this age range: 150 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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. 2. Other prior or ongoing medical conditions including: a. Acute illness within 4 weeks of the initial Screening visit; b. Abnormal physical findings, other than those associated with musculoskeletal findings attributable to DMD 3. Laboratory abnormality, that, in the Investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow-up would be completed, or impair the assessment of study results. These include, but are not limited to: a. Renal insufficiency; b. Impaired hepatic function glutamate dehydrogenase (GLDH) = 2.5x upper limit of normal (ULN) and bilirubin = 2x ULN (or International Normalized Ratio [INR] = 1.5x ULN); c. Activated partial thromboplastin time (aPTT) values above ULN; d. Platelet count 0.2 ng/mL 8. Need for daytime mechanical or non-invasive ventilation OR anticipated need for daytime mechanical or non-invasive ventilation within the next year, in the opinion of the Investigator. Nighttime non-invasive ventilation is permitted. 9. Changes in nutritional or herbal supplements or concomitant medications within 1 month prior to Screening visit or plans to modify (dose or regimen) during the study. 10. Currently on anticoagulants or drugs that are known to significantly increase the risk of bleeding, such as NSAIDs and heparin. 11. Received prior treatment with drisapersen or with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO). 12. Received prior treatment with WVE-210201. 13. Received prior treatment with gene therapy for DMD 14. Received treatment with ataluren or eteplirsen within the 14 weeks prior to the planned Baseline biopsy collection. 15. Received any investigational drug within 3 months or 5 half-lives, whichever is longer prior to the planned baseline biopsy collection. 16. Known hypersensitivity to any oligonucleotide, as demonstrated by a systemic allergic reaction such as changes in pulse, blood pressure, breathing function, etc. 17. Parent or legal guardian is directly or indirectly involved in the conduct and administration of this study as
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. Change from baseline in dystrophin level (% normal dystrophin) assessed by Western blot of muscle tissue (United States/Other regions, as applicable) 2. Change from baseline in NSAA at 48 weeks (EU/Japan) ; Timepoint(s) of evaluation of this end point: 1. 1 of 3 timepoints, week 12, week 22 or week 46 2. 48 weeks ; Main Objective: 1. To evaluate the efficacy of WVE-210201 by assessing changes in dystrophin levels (United States/Other regions, as applicable) 2. To evaluate the efficacy of WVE-210201 by assessing changes in motor function by North Star Ambulatory Assessment (NSAA) (European Union [EU]/Japan) ; Secondary Objective: 1. To evaluate the efficacy of WVE-210201 by assessing changes in upper limb proximal strength 2. To evaluate the efficacy of WVE-210201 by assessing changes in lower limb motor function 3. To evaluate the efficacy of WVE-210201 by assessing changes in respiratory function 4. To evaluate the efficacy of WVE-210201 by assessing changes in stride velocity 5. To evaluate the safety of WVE-210201 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Key secondary endpoint - Change from baseline in NSAA at 48 weeks (United States/Other regions as applicable) 2. Key secondary endpoint - Change from baseline dystrophin level (% normal dystrophin) assessed by Western blot of muscle tissue (EU/Japan) 3. Change from baseline in upper limb proximal strength assessed by hand held myometry at 48 weeks 4. Change from baseline in 4-stair climb (4SC) at 48 weeks 5. Change from baseline in the 10-meter walk/run test at 48 weeks 6. Change from baseline in FVC (% predicted) at 48 weeks 7. Change from baseline in the 95th percentile of stride velocity at 48 weeks ; Timepoint(s) of evaluation of this end point: 1. 48 weeks 2. 1 of 3 timepoints, week 12, week 22 or week 46 3. 48 weeks 4. 48 weeks 5. 48 weeks 6. 48 weeks 7. 48 weeks | — |
Countries
Australia, Belgium, Canada, Czech Republic, France, Germany, Ireland, Italy, Japan, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactAndrew Murphy
PPD
Outcome results
None listed