A Study to Assess Safety, Tolerability, and PK of EDG-5506 in Healthy Volunteers and Becker Muscular Dystrophy Adults

• ClinicalTrials.gov Identifier: NCT04585464
• Recruitment Status: Recruiting
• First Posted: October 14, 2020
• Last Update Posted: January 28, 2021
• Sponsor: Edgewise Therapeutics, Inc.
• Collaborator: Worldwide Clinical Trials
• Information provided by (Responsible Party): Edgewise Therapeutics, Inc.

Study Description

Brief Summary:

EDG-5506 is an investigational product intended to protect and improve function of dystrophic muscle fibers. This Phase 1 study of EDG-5506 will assess the safety, tolerability, and pharmacokinetics (PK) and of EDG-5506 in adult healthy volunteers and in adults with Becker muscular dystrophy (BMD).

Condition or disease	Intervention/treatment	Phase
Healthy Volunteer; Becker Muscular Dystrophy	Drug: EDG-5506; Drug: Placebo	Phase 1

Detailed Description:

Enrolled participants in this study will receive a single oral dose or multiple oral doses of EDG-5506 or a placebo. Blood and urine samples will be collected to measure how EDG-5506 is processed by the body and how the body responds when exposed to EDG-5506. Participants in the single ascending dose part of the study will remain in the clinic for 7 days with a 42-day follow-up period. Participants in the multiple ascending dose part of the study will remain in the clinic for 16 days with a 13-day follow-up period. Safety, tolerability, and pharmacokinetics of EDG-5506 will be assessed in healthy volunteers prior to enrolling participants with Becker muscular dystrophy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Placebo-Controlled, Double-blind, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and PK of EDG-5506 in Adult Healthy Volunteers and Adults With Becker Muscular Dystrophy
• Actual Study Start Date: October 12, 2020
• Estimated Primary Completion Date: October 2021
• Estimated Study Completion Date: October 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Healthy Volunteer: Single Ascending Dose; Single oral ascending dose in healthy volunteers Interventions: Drug: EDG-5506 Drug: Placebo	Drug: EDG-5506; EDG-5506 is administered orally as a single dose or once daily; Drug: Placebo; Placebo is administered orally as a single dose or once daily
Experimental: Healthy Volunteer: Multiple Ascending Dose; Multiple oral ascending doses in healthy volunteers Interventions: Drug: EDG-5506 Drug: Placebo	Drug: EDG-5506; EDG-5506 is administered orally as a single dose or once daily; Drug: Placebo; Placebo is administered orally as a single dose or once daily
Experimental: Becker Muscular Dystrophy: Multiple Ascending Dose; Multiple oral ascending doses in adults with Becker muscular dystrophy Interventions: Drug: EDG-5506 Drug: Placebo	Drug: EDG-5506; EDG-5506 is administered orally as a single dose or once daily; Drug: Placebo; Placebo is administered orally as a single dose or once daily

Outcome Measures

Primary Outcome Measures :

1. Incidence, frequency, severity and dose-relationship of adverse events [ Time Frame: Up to 42 days of monitoring ]
2. Incidence of abnormal laboratory test results (clinical chemistry, hematology, urinalysis, coagulation) [ Time Frame: Up to 42 days of monitoring ]
3. Incidence of treatment-emergent clinically abnormal electrocardiogram (ECG) [ Time Frame: Up to 42 days of monitoring ]
4. Incidence of abnormal vital signs [ Time Frame: Up to 42 days of monitoring ]
5. Incidence of abnormal physical exam findings [ Time Frame: Up to 42 days of monitoring ]

Secondary Outcome Measures :

1. Plasma maximum measured drug concentration (Cmax) [ Time Frame: Up to 42 days of testing ]
2. Time of maximum concentration (Tmax) [ Time Frame: Up to 42 days of testing ]
3. Area under the concentration-time curve (AUC) [ Time Frame: Up to 42 days of testing ]
4. Plasma half-life (T½) [ Time Frame: Up to 42 days of testing ]
5. Renal clearance (CLR) [ Time Frame: Up to 42 days of testing ]
6. Drug excreted unchanged in urine (Amt0-24) [ Time Frame: Up to 42 days of testing ]
7. Fraction excreted in urine (Fe) [ Time Frame: Up to 42 days of testing ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Healthy male and female (non-childbearing potential) volunteers and adult male Becker muscular dystrophy (BMD) participants
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male or female (HV only) adults aged 18 to 55 years, inclusive at the time of consent.
• For the healthy volunteer (HV) cohorts, good general health, with no significant medical history, no clinically significant abnormalities on physical examination at Screening and before administration of the initial dose of study drug.
• BMD patients must have medical records documenting pathological dystrophin mutation consistent with a diagnosis of BMD.
• BMD patients must have an ability to ambulate and an Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2.
• BMD patients must have a Baseline creatine kinase (CK) ≥ 1200 U/L.
• BMD patients must meet New York Heart Association (NYHA) Class 1 or 2 designation
• Body weight greater than or equal to 50 kg at the Screening visit.
• Body mass index between 18 and 30 kg/m2, inclusive.
• Screening or pre-dose forced vital capacity percent predicted >80% (Healthy and BMD patients).
• Female subjects must be of non-childbearing potential. They must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or post-menopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone in the post-menopausal range at Screening, based on the central laboratory's ranges.
• Male subjects with female partners must use a medically accepted contraceptive regimen from the first dose of study drug and for 90 days after the last administration of study drug. In addition, male subjects must not donate sperm for 6 months following his last day of dosing. Medically accepted contraceptive methods are defined as those with 90% or greater efficacy.
• Is currently a non-smoker and must not have used any tobacco products within 3 months prior to the Screening visit.
• Able and willing to attend the necessary visits at the study center.

Exclusion Criteria:

• History of, or physical exam findings indicating clinically significant endocrine, neurological, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases that, in the opinion of the investigator, would render the subject being unsuitable for the study.
• History of neoplastic disease (with the exception of adequately treated non-melanomatous skin carcinoma and treated cervical carcinoma in-situ).
• Fever (body temperature >38°C [>100°F]) or symptomatic viral/bacterial infection or use of antibiotics or antivirals within 2 weeks prior to Screening.
• Hospitalization or treatment of infection with parenteral antibiotics or antivirals within 45 days of Screening visit, and between Screening and admission to site.
• Pregnant or lactating females.
• Subject is unable to refrain from strenuous exercise for 3 days prior to check-in and during study.
• Have participated in any other investigational drug study within 30 days or 5 half-lives (whichever is longer) of dosing in the present study.

Contacts and Locations

Locations

United States, Texas

Worldwide Clinical Trials; Recruiting

San Antonio, Texas, United States, 78217

Contact: Lona Sheeran 830-399-9717 lona.sheeran@worldwide.com

Sponsors and Collaborators

Edgewise Therapeutics, Inc.

Worldwide Clinical Trials

Investigators

• Study Director: Medical Director; Edgewise Therapeutics, Inc.

More Information

Additional Information:

Sponsor Website 

• Responsible Party: Edgewise Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04585464
• Other Study ID Numbers: EDG-5506-001
• First Posted: October 14, 2020
• Last Update Posted: January 28, 2021
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Edgewise Therapeutics, Inc.:

Healthy Volunteers; Becker Muscular Dystrophy

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked