Clinical trial NCT05291091: Phase 2 Study of EDG-5506 in Becker Muscular Dystrophy (GRAND CANYON)
Official title: A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of EDG-5506 on Safety, Biomarkers, Pharmacokinetics, and Functional Measures in Adults and Adolescents With Becker Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Becker Muscular Dystrophy
Keywords: Becker Muscular Dystrophy
Lead sponsor: Edgewise Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
name: ImagingNMD
name: SYSNAV
First posted: 2022-03-22
Enrollment: 175
Sex: MALE
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: The CANYON Study including the adolescent cohorts are fully enrolled.

GRAND CANYON eligibility is listed below.

Key Inclusion Criteria:

1. 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.
2. Able to complete the 100-meter timed test in \< 200 seconds with or without use of mobility aid devices.
3. Able to perform the North Star Ambulatory Assessment scale and achieve a score of 5 to 32, inclusive.

Key Exclusion Criteria:

1. 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.
2. Cardiac echocardiogram ejection fraction \< 40%
3. Forced vital capacity predicted \<60% or using daytime ventilatory support
4. Receipt of oral corticosteroids for the treatment of BMD in the previous 6 months.
5. Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the screening visit in the present study.

Primary outcomes:
measure: Number of adverse events in those treated with sevasemten or placebo
timeFrame: 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6)
measure: Severity of adverse events in those treated with sevasemten or placebo
timeFrame: 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6)
measure: Change from Baseline in serum Creatine Kinase
timeFrame: 12 Months (CANYON Cohorts 1, 2)
measure: Change from Baseline in the North Star Ambulatory Assessment scale
timeFrame: 18 months (GRAND CANYON Cohort 6)
Secondary outcomes:
measure: Change from Baseline in the protein fast skeletal muscle Troponin I
timeFrame: 12 months (CANYON Cohorts 1, 2), 18 months (GRAND CANYON Cohort 6)
measure: Change from Baseline in the North Star Ambulatory Assessment scale
timeFrame: 12 Months (CANYON Cohorts 1, 2)
measure: Change from Baseline in the North Star Assessment for Limb-Girdle Type Muscular Dystrophies scale
timeFrame: 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6)
measure: Change from Baseline in the 10-meter walk/run test
timeFrame: 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6)
measure: Change from Baseline in 100-meter timed test
timeFrame: 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6)
measure: Change from Baseline in stride velocity (95th percentile)
timeFrame: 18 Months (GRAND CANYON Cohort 6)
measure: Pharmacokinetics as measured by steady state plasma concentration
timeFrame: 12 Months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6)
measure: Change from Baseline in growth as assessed by height centile on World Health Organization growth charts
timeFrame: 12 months (CANYON Cohorts 4, 5)
measure: Month 18 change from Baseline in fat fraction of upper leg muscles as assessed by Magnetic Resonance Imaging
timeFrame: 18 months (GRAND CANYON Cohort 6)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Neuroscience Health Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Aurora
country: United States
facility: UC Denver
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Hillsborough
country: United States
facility: Rare Disease Research, LLC NC
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Gardner Neuroscience Institute
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: National Neuromuscular Research Institute
state: Texas
city: Denton
country: United States
facility: Neurology Rare Disease Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Health
state: Virginia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Gent
country: Belgium
facility: University Hospital Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Régional de la Citadelle
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Marseille
country: France
facility: Centre de Reference des Maladies Neuromusculaires et de la SLA - AP-HM Hopital de La Timone
city: Nantes Cedex
country: France
facility: CHU de Nantes
city: Nice Cedex 1
country: France
facility: CHU de Nice - Hopital Pasteur 2 - Centre de reference des Maladies Neuromusculaires
city: Paris
country: France
facility: AP-HP Hopital Pitie-Salpetriere
city: Munich
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universitaet Muenchen
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Petah Tiqwa
country: Israel
facility: Schneider Children's Hospital of Israel
city: Milan
country: Italy
facility: Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano
city: Padova
country: Italy
facility: Azienda Ospedale - Università Padova
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: San Sebastian
country: Spain
facility: Hospital Universitario Donostia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: St. George's University Hospitals NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Newcastle Freeman Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
affiliation: Edgewise Therapeutics, Inc.
name: Joanne Donovan, MD, PhD
role: STUDY_CHAIR
affiliation: Edgewise Therapeutics, Inc.
name: Roxana D. Dreghici
role: STUDY_CHAIR
References: