A Study of EDG-5506 in Adult Males With Becker Muscular Dystrophy

Edgewise Therapeutics, Inc.12 enrolled

Overview

The ARCH study was an open-label, single-center, Phase 1b study of sevasemtem (EDG-5506) to assess the safety and pharmacokinetics (PK) of sevasemten in adults with Becker muscular dystrophy (BMD). Sevasemten is an investigational product intended to protect and improve function of dystrophic muscle fibers.

This open-label study evaluated the safety, tolerability, and pharmacokinetics (PK) of sevasemten in participants with BMD who completed the first-in-human study, EDG-5506-001, as well as additional (treatment-naïve) participants from outside the EDG-5506-001 study to meet the target sample size. All participants received sevasemten. This study had a 24 month treatment period, followed by an optional 4 week follow-up period. On-site visits occurred approximately monthly for the first 12 months, followed by every 3 months to assess safety and measures of function.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Becker Muscular Dystrophy

Interventions

SevasemtenDRUG

Daily oral dose of 10 mg daily until Visit 8 (Day 57), followed by 15 mg daily until Visit 13 (Month 6), followed by 20 mg until Visit 21 (Month 15), followed by 10 mg daily to Visit 27 (Month 24).

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participants who have completed Study EDG-5506-001. 2. Participants who were not from Study EDG-5506-001 must meet the following: 1. Male sex at birth and aged 18 to 55 years inclusive at time of consent. 2. Documented dystrophin mutation with phenotype consistent with BMD. 3. Ambulatory at Screening (defined as ability to complete 100 meter \[m\] timed test, with or without assistance). 4. Body weight ≥ 50 kg at the Screening visit. 5. Body mass index (BMI) between 20 and 34 kg/m2 inclusive. 3. Female sexual partners of male participants must use highly effective contraception (\<1% failure rate per year) through 6 months after last dose. 4. Capable of giving signed informed consent. Exclusion Criteria: 1. Any clinically significant changes during or following the completion of Study EDG 5506-001 that would affect the potential safety of the participant to receive EDG 5506. 2. Cardiac echocardiogram ejection fraction \<45% or New York Heart Association (NYHA) Class III or Class IV. 3. Baseline 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results. 4. Forced vital capacity (FVC) predicted \<65% or using daytime (mechanical or noninvasive) ventilatory support. 5. Moderate or severe renal or hepatic impairment (eGFR \<60 mL/min/1.73 m2). 6. Positive test for hepatitis C antibody (unless negative HCV PCR), hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody at screening. 7. History of substance abuse or dependency. 8. Receipt of oral corticosteroids for \>5 days in the previous 6 months at a dose of \>5 mg equivalent per day. Lower oral doses or inhaled/intranasal steroids are permitted. 9. Receiving moderate or strong cytochrome P450 CYP3A4 inhibitors or inducers. 10. Participation in any other investigational drug study or use of use of an investigational drug within 30 days or 5 half-lives (whichever is longer) of dosing in the present study. 11. Participants who are unlikely to comply with the study protocol or, in the opinion of the Investigator, would not be a suitable candidate for participation in the study. 12. Medical history or other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory result or abnormality that may increase the risk of study participation or, in the Investigator's judgment, make the participant inappropriate for the study. Includes venous access that would be too difficult to facilitate repeated blood sampling.

Locations (1)

Rare Disease Research

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Percentage of Participants Treated With Sevasemten Experiencing AEs

An AE is any untoward medical occurrence in a patient administered a medicinal product. The AE does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The numerator of the percentage is the number of participants experiencing at least one AE after first dose of study drug up to 25 months.

Time frame: From first dose of study drug to 25 months

Frequency of AEs in Those Treated With Sevasemten

An AE is any untoward medical occurrence in a patient administered a medicinal product. The AE does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The endpoint is the cumulative total number of AEs occurring after first dose of study drug up to 25 months among participants who received at least one dose of study drug.

Time frame: From first dose of study drug to 25 months

Number of Participants Treated With Sevasemten With AEs by Maximum Severity

An AE is any untoward medical occurrence in a patient administered a medicinal product. The AE does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of an AE is graded, according to the study protocol definitions of AE severity/intensity, as "mild", "moderate" or "severe". Participants who reported multiple AEs are counted only once at the highest severity reported.

Time frame: From first dose of study drug to 25 months

Secondary Outcomes

Data from ClinicalTrials.gov

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Percentage of Participants Experiencing Treatment-Emergent Abnormal Clinical Chemistry Test Results

Treatment-emergent defined as any event that occurs after the start of study drug or was present at baseline and worsened after taking study drug. The numerator of the percentage is the number of participants experiencing at least one treatment-emergent abnormal clinical chemistry test result after first dose of study drug up to 25 months.

Time frame: From first dose of study drug to 25 months

Percentage of Participants Experiencing Treatment-Emergent Abnormal Hematology Test Results

Treatment-emergent defined as any event that occurs after the start of study drug or was present at baseline and worsened after taking study drug. The numerator of the percentage is the number of participants experiencing at least one treatment-emergent abnormal hematology test result after first dose of study drug up to 25 months.

Time frame: From first dose of study drug to 25 months

Percentage of Participants Experiencing Treatment-Emergent Abnormal Coagulation Test Results

Treatment-emergent defined as any event that occurs after the start of study drug or was present at baseline and worsened after taking study drug. The numerator of the percentage is the number of participants experiencing at least one treatment-emergent abnormal coagulation test result after first dose of study drug up to 25 months.

Time frame: From first dose of study drug to 25 months

Percentage of Participants Experiencing Treatment-Emergent Abnormal Urinalysis Test Results

Treatment-emergent defined as any event that occurs after the start of study drug or was present at baseline and worsened after taking study drug. The numerator of the percentage is the number of participants experiencing at least one treatment-emergent abnormal urinalysis test result after first dose of study drug up to 25 months.

Time frame: From first dose of study drug to 25 months

Number of Participants With Clinically Significant Changes in Clinical Chemistry

Refer to Protocol for list of clinical chemistry tests that were performed. Clinically significant changes in clinical chemistry are defined as adverse events related to clinical chemistry tests or investigator identified results reported from first dose of study drug up to 24 months. Only clinically significant changes were counted.