A Study of CK-2127107 in Patients With Spinal Muscular Atrophy

NCT ID: NCT02644668

Last Updated: 2020-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-14
• Study Completion Date: 2018-05-31

Brief Summary

This study will evaluate the pharmacodynamic (PD) effect of CK-2127107 (hereafter referred to as reldesemtiv) versus placebo on measures of skeletal muscle function or fatigability in patients with Type II, III, or IV spinal muscular atrophy (SMA).

Detailed Description

CY 5021 is a Phase 2, double-blind, randomized, placebo-controlled, multiple dose study of reldesemtiv in 2 sequential ascending dose cohorts of patients with SMA. Patients will be randomized 2:1 to receive reldesemtiv or placebo twice daily for 8 weeks. Patients randomized to reldesemtiv in Cohort 1 will receive a dose of 150 mg twice daily and patients randomized to reldesemtiv in Cohort 2 will receive 450 mg twice daily. Within each cohort, randomization will be stratified by ambulatory status (ambulatory versus non ambulatory).

The primary objective of the study is to determine the PD effects of reldesemtiv on measures of pulmonary function, respiratory function, muscle strength, and motor function. Other PD measures include changes in the timed up and go (TUG) test, a 6-minute walk test (6MWT), and patient and investigator global assessments. Secondary objectives include the safety of multiple doses of reldesemtiv and an evaluation of the pharmacokinetics of reldesemtiv.

Conditions

Spinal Muscular Atrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Patients randomized to this treatment arm will receive a placebo suspension twice daily for 8 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Granules for oral suspension (placebo)

Reldesemtiv 150 mg twice daily

Patient randomized to this treatment arm will receive reldesemtiv suspension at a dose of 150 mg, twice daily for 8 weeks.

Group Type: EXPERIMENTAL

Reldesemtiv 150 mg

Intervention Type: DRUG

Granules for oral suspension, 18.7% reldesemtiv

Reldesemtiv 450 mg twice daily

Patients randomized to this treatment arm will receive reldesemtiv suspension at a dose of 450 mg, twice daily for 8 weeks.

Group Type: EXPERIMENTAL

Reldesemtiv 450 mg

Intervention Type: DRUG

Granules for oral suspension, 56.0% reldesemtiv

Interventions

Placebo

Granules for oral suspension (placebo)

Intervention Type: DRUG

Reldesemtiv 150 mg

Granules for oral suspension, 18.7% reldesemtiv

Intervention Type: DRUG

Reldesemtiv 450 mg

Granules for oral suspension, 56.0% reldesemtiv

Intervention Type: DRUG

Other Intervention Names

CK-2127107; CK-2127107

Eligibility Criteria

Inclusion Criteria

• Able to comprehend and willing to sign an Informed Consent Form (ICF) for patients 18 years of age and older. For patients less than 18 years of age, parent(s)/legal guardian(s) of patients must provide written informed consent prior to participation in the study and informed assent will be obtained from minors at least 12 years of age when required by regulation.
• Males or females with genetically confirmed diagnosis of SMA who are Type II, III or IV and at least 12 years of age
• Ambulatory patients, once having achieved a standing position independently, must be able to complete at least one lap in the 6-minute walk test (at least 50 meters) within 6 minutes without assistance.
• Non-ambulatory patients (defined as individuals who are effectively requiring a wheelchair for all mobility needs; they may be able to stand or walk short distances, but unable to walk 50 meters without assistance in 6 minutes). Non-ambulatory patients must be able to tolerate an upright sitting position, with support, continuously for 3 hours
• Hammersmith (HFMS-E) score ≥ 10 and ≤ 54
• Contracture of the elbow flexion and knee flexion ≤ 90 degrees
• Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
• Able to swallow an oral suspension and in the opinion of the Investigator, is expected to continue to be able to do so for the duration of the trial. Administration via a feeding tube is not allowed.
• Forced vital capacity (FVC) > 20% predicted
• Male patients who have reached puberty must agree to do either of the following from Screening until 10 weeks after the last dose of the investigational product unless they have had a vasectomy and confirmed sperm count is zero:

• Abstain from sexual intercourse, OR
• If having heterosexual intercourse, must use a condom and their female partners who are of childbearing potential must use a highly effective contraception method*
• Female patients who have had their first period will be considered of childbearing potential unless they are anatomically and physiologically incapable of becoming pregnant. If of childbearing potential, the female patients must:

• Have a negative urine/serum pregnancy test at Screening AND
• Abstain from heterosexual intercourse from Screening until 10 weeks after the last dose of investigational product OR
• If having heterosexual intercourse, must use a highly effective contraception method* and require the male partners to use a condom from Screening until 10 weeks after the last dose of investigational product

*Highly effective contraception methods include:

• Established use of oral, injected or implanted hormonal methods of contraception
• Placement of an intrauterine device (IUD) or intrauterine system (IUS)
• Male patients must agree to refrain from sperm donation from Screening until 10 weeks after the final study drug administration

Exclusion Criteria

• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator
• Hospitalization within 2 months of Screening
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
• A clinically significant illness within 4 weeks of Screening
• History of alcoholism or drug addiction within 2 years prior to Screening
• History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to Screening
• Patient has used a strong CYP3A4 inhibitor within 7 days prior to first dose of study drug or a strong CYP3A4 inducer within 14 days prior to first dose of study drug
• Any other medical condition that would interfere with performance of testing including (but not limited to) significant joint pain or arthritis limiting mobility, and chronic neuromuscular pain sufficient to require ongoing analgesic medication
• Participation by two people at the same time that are living in the same household
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days or five half-lives of the other investigational study drug, whichever is greater, prior to Screening
• An ALT or AST greater than 2-fold the upper limit of normal (ULN) or has total bilirubin greater than the ULN at screening. These assessments may be repeated once at the investigator's discretion (within the screening window)
• Currently taking nusinersen, or has taken it in the past, or plans to take it during the course the study

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: collaborator

Cytokinetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD, Cytokinetics

Role: STUDY_DIRECTOR

Cytokinetics, Inc.

Locations

UCLA

Los Angeles, California, United States

University of California Irvine

Orange, California, United States

Pediatric Neuromuscular Clinic Stanford University

Palo Alto, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Hospital for Special Care

New Britain, Connecticut, United States

Nemours Childrens Hospital

Orlando, Florida, United States

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins Hospital Institute for Clinical and Translational Research Pediatric Clinical Research Unit

Baltimore, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

The University of Utah, Clinical Neurosciences Center

Salt Lake City, Utah, United States

Alberta Children's Hospital

Calgary, Alberta, Canada

Children's and Women's Health Centre of British Columbia

Vancouver, British Columbia, Canada

Children's Hospital - LHSC

London, Ontario, Canada

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CY 5021

Identifier Type: -

Identifier Source: org_study_id