Phase 2 Study of EDG-5506 in Becker Muscular Dystrophy (GRAND CANYON)

• ClinicalTrials.gov Identifier: NCT05291091
• Recruitment Status: Recruiting
• First Posted: March 22, 2022
• Last Update Posted: May 13, 2024
• Sponsor: Edgewise Therapeutics, Inc.
• Collaborators: Medpace, Inc.; ImagingNMD; SYSNAV
• Information provided by (Responsible Party): Edgewise Therapeutics, Inc.

Tracking Information

• First Submitted Date: March 14, 2022
• First Posted Date: March 22, 2022
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: July 6, 2022
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2024)

• Number of adverse events in those treated with sevasemten or placebo [ Time Frame: 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 [ Time Frame: 12 months (CANYON Cohorts 1, 2, 4, 5), 18 months (GRAND CANYON Cohort 6) ]
  All participants
• Change from Baseline in serum Creatine Kinase [ Time Frame: 12 Months (CANYON Cohorts 1, 2) ]
  Adult participants
• Change from Baseline in the North Star Ambulatory Assessment scale [ Time Frame: 18 months (GRAND CANYON Cohort 6) ]
  Adult participants

Original Primary Outcome Measures (submitted: March 14, 2022)

• Number of AEs in those treated with EDG-5506 or placebo [ Time Frame: 12 months ]
  All participants
• Severity of AEs in those treated with EDG-5506 or placebo [ Time Frame: 12 months ]
  All participants
• Change from Baseline in serum Creatine Kinase (CK) [ Time Frame: 12 Months ]
  Adult participants

Current Secondary Outcome Measures (submitted: September 11, 2023)

• Change from Baseline in the protein fast skeletal muscle Troponin I [ Time Frame: 12 months (CANYON Cohorts 1, 2), 18 months (GRAND CANYON Cohort 6) ]
  Adult participants
• Change from Baseline in the North Star Ambulatory Assessment scale [ Time Frame: 12 Months (CANYON Cohorts 1, 2) ]
  Adult participants
• Change from Baseline in the North Star Assessment for Limb-Girdle Type Muscular Dystrophies scale [ Time Frame: 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) ]
  Adult participants
• Change from Baseline in the 10-meter walk/run test [ Time Frame: 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) ]
  Adult participants
• Change from Baseline in 100-meter timed test [ Time Frame: 12 Months (CANYON Cohorts 1, 2), 18 Months (GRAND CANYON Cohort 6) ]
  Adult participants
• Change from Baseline in stride velocity (95th percentile) [ Time Frame: 18 Months (GRAND CANYON Cohort 6) ]
  Adult participants
• Pharmacokinetics as measured by steady state plasma concentration [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 18 months (GRAND CANYON Cohort 6) ]
  Adult participants

Original Secondary Outcome Measures (submitted: March 14, 2022)

• Change from Baseline in fat fraction of upper leg muscles assessed by Magnetic Resonance Imaging [ Time Frame: 12 Months ]
  Adult participants
• Change from Baseline in North Star Ambulatory Assessment (NSAA) [ Time Frame: 12 Months ]
  Adult participants
• Change from Baseline in the 10-meter walk/run test [ Time Frame: 12 Months ]
  Adult participants
• Change from Baseline in 100-meter timed test [ Time Frame: 12 Months ]
  Adult participants
• Change from Baseline in 4-stair climb [ Time Frame: 12 Months ]
  Adult participants
• Pharmacokinetics as measured by steady state plasma concentration [ Time Frame: 12 Months ]
  All participants

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Becker Muscular Dystrophy

Intervention

• Drug: Sevasemten 10 mg
  Sevasemten is administered orally once per day
• Drug: Sevasemten 5 mg
  Sevasemten is administered orally once per day
• Drug: Sevasemten 12.5 mg
  Sevasemten is administered orally once per day
• Drug: Placebo
  Placebo is administered orally once per day

Study Arms

• Experimental: Adult Cohort 1
  Drug: Sevasemten Drug: Placebo
  Interventions:

  • Drug: Sevasemten 10 mg
  • Drug: Placebo
• Experimental: Adult Cohort 2
  Drug: Sevasemten Drug: Placebo
  Interventions:

  • Drug: Sevasemten 10 mg
  • Drug: Placebo
• Experimental: Adult Cohort 6
  Drug: Sevasemten Drug: Placebo
  Interventions:

  • Drug: Sevasemten 10 mg
  • Drug: Placebo
• Experimental: Adolescent Cohort 4
  Drug: Sevasemten Drug: Placebo
  Interventions:

  • Drug: Sevasemten 5 mg
  • Drug: Placebo
• Experimental: Adolescent Cohort 5
  Drug: Sevasemten Drug: Placebo
  Interventions:

  • Drug: Sevasemten 12.5 mg
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 11, 2023): 170
• Original Estimated Enrollment (submitted: March 14, 2022): 54
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 12 Years to 50 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Edgewise Therapeutics; 720-262-7002; studies@edgewisetx.com

• Listed Location Countries: Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT05291091
• Other Study ID Numbers: EDG-5506-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Edgewise Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Edgewise Therapeutics, Inc.
• Original Study Sponsor: Same as current

Collaborators

• Medpace, Inc.
• ImagingNMD
• SYSNAV

Investigators

• Study Chair: Joanne Donovan, MD, PhD; Edgewise Therapeutics, Inc.
• Study Chair: Roxana D. Dreghici; Edgewise Therapeutics, Inc.

• PRS Account: Edgewise Therapeutics, Inc.
• Verification Date: May 2024