Phase 2 Study of EDG-5506 in Becker Muscular Dystrophy (GRAND CANYON)
- Conditions
- Becker Muscular Dystrophy
- Interventions
- Drug: Sevasemten 10 mgDrug: Sevasemten 5 mgDrug: Sevasemten 12.5 mgDrug: Placebo
- Registration Number
- NCT05291091
- Lead Sponsor
- Edgewise Therapeutics, Inc.
- Brief Summary
A study of sevasemten (EDG-5506) in Becker muscular dystrophy (known as CANYON) and pivotal cohort (known as GRAND CANYON). The EDG-5506-201 CANYON study was expanded to include an additional 120 adult participants in a cohort called GRAND CANYON, that is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of sevasemten in adults with Becker.
CANYON is fully enrolled; GRAND CANYON is currently enrolling.
- Detailed Description
The EDG-5506-201 protocol was amended to include an additional cohort thus consists of two parts.
Part 1: CANYON is a double-blind, randomized, placebo-controlled design to investigate the effect of sevasemten on the safety, pharmacokinetics, biomarkers, and functional measures. Approximately 32 adults and 18 adolescents with Becker muscular dystrophy are planned to enroll in this study. This study will have up to a 4-week Screening period, a 12-month Treatment period, followed by a 4-week follow-up period.
Approximately 32 adult participants will randomize to Cohort 1 or Cohort 2 in a 1:1 ratio then each cohort will further randomize to sevasemten or placebo in a 3:1 ratio.
Approximately 9 adolescent participants will enroll in Cohort 4 and randomize in a 2:1 ratio to sevasemten or placebo. Cohort 5 will randomize an additional 9 participants in a 2:1 ratio to either sevasemten or placebo after Cohort 4.
CANYON is now fully enrolled.
Part 2: GRAND CANYON or Cohort 6 is a double-blind, randomized, placebo-controlled design to investigate the safety and efficacy of sevasemten in adults with Becker muscular dystrophy after 18 months of treatment. Approximately 120 adults with Becker muscular dystrophy are planned to enroll in this study. This study will have up to a 4-week Screening period, an 18-month Treatment period, followed by a 4-week follow-up period.
Approximately 120 adult participants will be randomized in Cohort 6 in a 2:1 ratio either to sevasemten or placebo.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 175
- Adults (aged 18 to 50 years, inclusive) with a documented dystrophin mutation and phenotype consistent with Becker muscular dystrophy, and history of being ambulatory beyond 16 years of age without steroids; history of being ambulatory beyond 18 years of age with steroids.
- Able to complete the 100-meter timed test in < 200 seconds with or without use of mobility aid devices.
- Able to perform the North Star Ambulatory Assessment scale and achieve a score of 5 to 32, inclusive.
Key
- Medical history or clinically significant physical examination/laboratory result that, in the opinion of the investigator, would render the participant unsuitable for the study. This includes contraindications to magnetic resonance imaging such as non-compatible implanted medical devices or severe claustrophobia.
- Cardiac echocardiogram ejection fraction < 40%
- Forced vital capacity predicted <60% or using daytime ventilatory support
- Receipt of oral corticosteroids for the treatment of BMD in the previous 6 months.
- Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the screening visit in the present study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Adult Cohort 2 Placebo Drug: Sevasemten Drug: Placebo Adult Cohort 6 Sevasemten 10 mg Drug: Sevasemten Drug: Placebo Adult Cohort 6 Placebo Drug: Sevasemten Drug: Placebo Adolescent Cohort 4 Sevasemten 5 mg Drug: Sevasemten Drug: Placebo Adolescent Cohort 4 Placebo Drug: Sevasemten Drug: Placebo Adolescent Cohort 5 Sevasemten 12.5 mg Drug: Sevasemten Drug: Placebo Adolescent Cohort 5 Placebo Drug: Sevasemten Drug: Placebo Adult Cohort 1 Placebo Drug: Sevasemten Drug: Placebo Adult Cohort 2 Sevasemten 10 mg Drug: Sevasemten Drug: Placebo Adult Cohort 1 Sevasemten 10 mg Drug: Sevasemten Drug: Placebo
- Primary Outcome Measures
Name Time Method Number of adverse events in those treated with sevasemten or placebo 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) All participants
Severity of adverse events in those treated with sevasemten or placebo 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) All participants
Change from Baseline in serum Creatine Kinase 12 Months (CANYON Cohorts 1, 2) Adult participants
Change from Baseline in the North Star Ambulatory Assessment scale 18 months (GRAND CANYON Cohort 6) Adult participants
- Secondary Outcome Measures
Name Time Method Change from Baseline in the protein fast skeletal muscle Troponin I 12 months (CANYON Cohorts 1, 2), 18 months (GRAND CANYON Cohort 6) Adult participants
Change from Baseline in the North Star Ambulatory Assessment scale 12 Months (CANYON Cohorts 1, 2) Adult participants
Change from Baseline in the North Star Assessment for Limb-Girdle Type Muscular Dystrophies scale 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) Adult participants
Change from Baseline in the 10-meter walk/run test 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) Adult participants
Change from Baseline in 100-meter timed test 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) Adult participants
Change from Baseline in stride velocity (95th percentile) 18 Months (GRAND CANYON Cohort 6) Adult participants
Pharmacokinetics as measured by steady state plasma concentration 12 Months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) All participants
Change from Baseline in growth as assessed by height centile on World Health Organization growth charts 12 months (CANYON Cohorts 4, 5) Adolescent participants
Month 18 change from Baseline in fat fraction of upper leg muscles as assessed by Magnetic Resonance Imaging 18 months (GRAND CANYON Cohort 6) Adult participants
Trial Locations
- Locations (51)
UC Denver
🇺🇸Aurora, Colorado, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Rare Disease Research
🇺🇸Atlanta, Georgia, United States
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
🇩🇪Munich, Germany
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Schneider Children's Hospital of Israel
🇮🇱Petah Tiqwa, Israel
Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milan, Italy
Azienda Ospedale - Università Padova
🇮🇹Padova, Italy
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Optimal Clinical Trials
🇳🇿Auckland, New Zealand
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
St. George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Hospital Universitario Donostia
🇪🇸San Sebastian, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
University College London Hospital
🇬🇧London, United Kingdom
Newcastle Freeman Hospital
🇬🇧Newcastle, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom
Kennedy Krieger Institute
🇺🇸Baltimore, Maryland, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
UC San Diego
🇺🇸La Jolla, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Stanford Neuroscience Health Center
🇺🇸Palo Alto, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Rare Disease Research, LLC NC
🇺🇸Hillsborough, North Carolina, United States
University of Cincinnati Gardner Neuroscience Institute
🇺🇸Cincinnati, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
National Neuromuscular Research Institute
🇺🇸Austin, Texas, United States
Neurology Rare Disease Center
🇺🇸Denton, Texas, United States
Virginia Commonwealth University Health
🇺🇸Richmond, Virginia, United States
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Australia
University Hospital Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Régional de la Citadelle
🇧🇪Liège, Belgium
Rigshospitalet
🇩🇰Copenhagen, Denmark
Centre de Reference des Maladies Neuromusculaires et de la SLA - AP-HM Hopital de La Timone
🇫🇷Marseille, France
CHU de Nantes
🇫🇷Nantes Cedex, France
CHU de Nice - Hopital Pasteur 2 - Centre de reference des Maladies Neuromusculaires
🇫🇷Nice Cedex 1, France
AP-HP Hopital Pitie-Salpetriere
🇫🇷Paris, France