Phase 2 Randomized, Double-blind, Placebo-controlled Study of the Effect of EDG-5506 on Biomarkers in Adults with Neuromuscular Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Edgewise Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

6 Dec 2022 → 25 Nov 2025

Decision date (initial)

2022-10-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Edgewise Therapeutics

External identifiers

EU CT number

2022-500215-39-00

WHO UTN

U1111-1280-4570

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Others

To assess the safety of sevasemten in adults with neuromuscular disease.
To assess the effect of sevasemten treatment on biomarkers of muscle damage in adults with Becker Muscular Dystrophy (BMD), McArdle disease, or Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I).

Secondary objectives 3

1. To assess biomarker response to sevasemten treatment in adults with BMD, McArdle disease, or LGMD2I.
2. To assess the change in individual safety parameters in adults with BMD, McArdle disease, or LGMD2I.
3. To evaluate the pharmacokinetics of sevasemten concentrations in adults with BMD, McArdle disease, or LGMD2I.

Conditions and MedDRA coding

McArdle Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Participants with BMD or LGMD2I must be 18 to 65 years of age inclusive, at the time of signing the informed consent. Participants with McArdle disease may enroll up to 75 years of age inclusive, at the time of signing the informed consent form.
2. 2. Participant has a molecular diagnosis of BMD (a documented dystrophin mutation and phenotype consistent with BMD, and history of being ambulatory beyond 16 years of age without steroids; history of being ambulatory beyond 18 years of age with steroids), McArdle disease, or LGMD2I with a consistent clinical phenotype.
3. 3. Participant is able to comply with the cycle exercise protocol (in the opinion of the Principal Investigator).
4. 4. Participant has no concurrent medical condition that would, in the opinion of the Investigator, impair the ability to give informed consent or undertake any of the protocol-mandated visits/assessments.
5. 5. Participant has no active muscle injury at Screening.
6. 6. Participant is willing and able to comply with all protocol requirements.
7. 7. Participant is able to converse and read fluently in Danish or English.
8. 8. Participant is willing to comply with contraception requirements described in protocol.
9. 9. Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 12

1. 1. Medical history, clinically significant laboratory, or physical examination finding that, in the opinion of the Investigator, would render the participant unsuitable for the study. This includes anything that would prevent completion of the cycle ergometer test.
2. 09. Current use of any strong or moderate cytochrome P450 (CYP)3A4 inhibitors or inducers.
3. 10. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, recent (within the past year) history of substance abuse or dependency or laboratory results or abnormality that may increase the risk of study participation or, in the Investigator’s judgment, make the participant inappropriate for the study.
4. 11. Participation in a previous exercise challenge study if the challenge itself has taken place less than 10 weeks prior to screening.
5. 12. Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of dosing in the present study.
6. 2. Left ventricular ejection fraction <45% or New York Heart Association (NYHA) Class III or Class IV, determined by local read.
7. 3. 12-lead electrocardiogram (ECG) demonstrating clinically relevant abnormalities that may affect participant safety or interpretation of study results, determined by local read.
8. 4. Forced vital capacity (FVC) predicted <60% or using daytime (mechanical or noninvasive) ventilatory support.
9. 5. Moderate or severe hepatic impairment
10. 6. Moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 ). eGFR will be based on Cystatin C formula (eGFR = 133 x min(Scys/0.8, 1)^-0.499 x max (Scys/0.8, 1)^-1.328 X 0.996^Age x 0.932 [if female].
11. 7. Positive test for hepatitis C antibody (unless negative hepatitis C virus polymerase chain reaction), hepatitis B surface antigen, or human immunodeficiency virus antibody.
12. 8. Receipt of oral corticosteroids for >10 days in the previous 6 months. Inhaled/intranasal steroids are permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence, frequency, and severity of adverse events and serious adverse events in those treated with EDG-5506 or placebo.
2. Change in serum creatine kinase (CK) from baseline to week 16.

Secondary endpoints 3

1. Change in serum CK from pre-exercise baseline to week 52.
2. Incidence of treatment-emergent abnormal laboratory test results (clinical chemistry, hematology, and urinalysis). Change from Baseline in: - Safety laboratory parameters - Vital signs - Physical and neurological examination - Electrocardiogram (ECG) parameters - Cardiac function as assessed by echocardiogram - Pulmonary function as assessed by spirometry (FEV1,FVC) - C-SSRS (Columbia Suicide Severity Rating Scale)
3. Steady state plasma concentrations of sevasemten

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Edgewise Therapeutics Inc.

Sponsor organisation

Edgewise Therapeutics Inc.

Address

1715 38th Street

City

Boulder

Postcode

80301-2603

Country

United States

Scientific contact point

Organisation

Edgewise Therapeutics Inc.

Contact name

Edgewise Clinical Studies

Public contact point

Organisation

Edgewise Therapeutics Inc.

Contact name

Edgewise Clinical Studies

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications