Study of Safety, Tolerability & Efficacy of CK-2017357 in Amyotrophic Lateral Sclerosis (ALS)

NCT ID: NCT01709149

Last Updated: 2020-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 711 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-03-31

Brief Summary

The purpose of this research study is to evaluate the safety and effectiveness of CK-2017357 when taken with or without riluzole (also called Rilutek®) in patients with Amyotrophic Lateral Sclerosis (ALS).

Detailed Description

The length of the study, including screening, dosing, and follow-up, is approximately 20 weeks. After a one-week open-label phase during which all patients will receive CK-2017357 125 milligrams (mg) twice daily, patients who tolerate the open-label 125 mg of CK-2017357 will be randomized one to one (fifty-fifty) to receive double-blind CK-2017357 or matching placebo. The CK-2017357/placebo dose will be increased no faster than weekly to each patient's highest tolerated daily dose, with a maximum of 250 mg twice daily. The dose may be decreased based on tolerability. Patients will continue treatment at the highest tolerated dose to complete a total of 12 weeks of double-blind treatment. Patients may be on riluzole or not on riluzole at study entry. Patients not on riluzole must stay off riluzole. Patients on riluzole who are getting double-blind CK-2017357 will be given riluzole at half the labeled dosage (50 mg once a day instead of 50 mg twice a day). Blood tests for safety will be performed. Information about any side effects that may occur will also be collected.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

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

Study Groups

CK-2017357

125 mg tablets

Group Type: EXPERIMENTAL

CK-2017357

Intervention Type: DRUG

CK-2017357 125 mg tablets twice daily

Riluzole

Intervention Type: DRUG

Tablets

Placebo

Placebo tablets

Group Type: PLACEBO_COMPARATOR

Placebo tablets

Intervention Type: OTHER

Tablets

Riluzole

Intervention Type: DRUG

Tablets

Interventions

CK-2017357

CK-2017357 125 mg tablets twice daily

Intervention Type: DRUG

Placebo tablets

Tablets

Intervention Type: OTHER

Riluzole

Tablets

Intervention Type: DRUG

Other Intervention Names

tirasemtiv; Rilutek

Eligibility Criteria

Inclusion Criteria

1. Able to comprehend and willing to sign an Informed Consent Form (ICF)

2. Male or female 18 years of age or older

3. A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria)

4. Upright Slow Vital Capacity (SVC) >50 % of predicted for age, height and sex

5. At least 4 of the 12 ALSFRS-R questions must be scored 2 or 3

6. Diminished but measurable maximum voluntary grip strength in at least one hand; i.e., between 10 and 50 pounds (females) and 10 and 70 pounds (males)

7. Able to swallow tablets without crushing

8. A caregiver (if one is needed) who can and will observe and report the patient's status

9. Pre-study clinical laboratory findings within normal range or, if outside of the normal range, deemed not clinically significant by the Investigator

10. Male patients must agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) or the male patient must agree to abstain from sexual intercourse during and for 10 weeks after the end of the study

11. Female patients must be post-menopausal (≥ 1 year) or sterilized, or, if of childbearing potential, not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the course of the study, and use contraceptive drugs or devices as detailed in item 10 for the duration of the study and for 10 weeks after the end of the study

12. Patients must be either on a stable dose of riluzole 50 mg twice daily for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and are willing not to begin riluzole use during the conduct of this study.

Exclusion Criteria

1. Any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation

2. Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS placement during the course of the study

3. Body Mass Index (BMI) of 19.0 kg/m2 or lower

4. Unwilling to discontinue tizanidine and theophylline-containing medications during study participation

5. Serum chloride < 100 mmol/L

6. Neurological impairment due to a condition other than ALS, including history of transient ischemic attack (TIA) within the past year

7. Presence at screening of any medically significant cardiac, pulmonary, gastrointestinal (GI), musculoskeletal, or psychiatric illness that might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety or efficacy data

8. Has taken any investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing

9. Previously received CK-2017357 in any previous clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cytokinetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jinsy Andrews, MD

Role: STUDY_DIRECTOR

Cytokinetics, Inc.

Jeremy Shefner, MD, PhD

Role: STUDY_CHAIR

State University of New York - Upstate Medical University

Jeremy Shefner, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

State University of New York - Upstate Medical University

Locations

Barrow Neurology

Phoenix, Arizona, United States

University of California, San Diego

La Jolla, California, United States

UC Irvine ALS & Neuromuscular Center

Orange, California, United States

Coordinated Clinical Research

San Diego, California, United States

California Pacific Medical Center Forbes Norris MDA/ALS Research Center

San Francisco, California, United States

Hospital for Special Care

New Britain, Connecticut, United States

The George Washington University

Washington D.C., District of Columbia, United States

Mayo Clinic Florida Department of Neurology

Jacksonville, Florida, United States

Emory University, School of Medicine

Atlanta, Georgia, United States

Georgia Health Sciences University

Augusta, Georgia, United States

Indiana University Department of Neurology

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas

Kansas City, Kansas, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

St Mary's Healthcare

Grand Rapids, Michigan, United States

Hennepin County Medical Center - Berman Center for Research

Minneapolis, Minnesota, United States

Saint Louis University

St Louis, Missouri, United States

Washington University

St Louis, Missouri, United States

Neurology Associates

Lincoln, Nebraska, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Hospital for Special Surgery

New York, New York, United States

University of Rochester

Rochester, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Carolinas Medical Center Department of Neurology

Charlotte, North Carolina, United States

Duke University

Durham, North Carolina, United States

Wake Forest University, School of Medicine

Winston-Salem, North Carolina, United States

Ohio State University Department of Neurology

Columbus, Ohio, United States

Providence ALS Center

Portland, Oregon, United States

Oregon Health & Science University

Portland, Oregon, United States

Penn State Hershey Neuroscience Clinics

Hershey, Pennsylvania, United States

Drexel Neurology

Philadelphia, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Neurology

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

UTHSCSA Department of Neurology

San Antonio, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

West Virginia University Department of Neurology

Morgantown, West Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Heritage Medical Research

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

University of British Columbia

Vancouver, British Columbia, Canada

Stan Cassidy Centre for Rehabilitation

Fredericton, New Brunswick, Canada

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

McMaster University Medical Centre

Hamilton, Ontario, Canada

Queen's University : Kingston General

Kingston, Ontario, Canada

London Health Sciences

London, Ontario, Canada

Univ. of Toronto - Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Hôpital Notre Dame (CHUM) Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Montreal Neurological Institute

Montreal, Quebec, Canada

CHU de Quebec: Hopital l'Enfant-Jesus

Québec, Quebec, Canada

CHRU de Lille - Hôpital Roger Salengro

Lille, , France

CHU de Limoges - Hôpital Dupuytren

Limoges, , France

Hôpital La Timone Adulte

Marseille, , France

CHU Montepellier

Montpellier, , France

Hôpital Archet 1

Nice, , France

Hôpital de la Salpêtrière

Paris, , France

Hôpital Bretonneau

Tours, , France

Charite Universitätsmedizin

Berlin, , Germany

Hannover Medical School

Hanover, , Germany

University of Ulm

Ulm, , Germany

Trinity College, Beaumont Hospital

Dublin, , Ireland

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Hospital Carlos III

Madrid, , Spain

Barts and the London MND & the Centre Royal London Hospital

Whitechapel, London, United Kingdom

Walton Centre for Neurology and Neurosurgery

Liverpool, , United Kingdom

Kings College Hospital NHS Foundation Trust

London, , United Kingdom

John Radcliffe Hospital

Oxford, , United Kingdom

Plymouth Hospitals NHS Trust

Plymouth, , United Kingdom

Sheffield Institute for Translational Neuroscience

Sheffield, , United Kingdom

Countries

United States; Canada; France; Germany; Ireland; Netherlands; Spain; United Kingdom

Other Identifiers

CY 4026

Identifier Type: -

Identifier Source: org_study_id