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

NCT01709149 | Completed Phase 2 Results DMC

• 1 other identifier: CY 4026
• Study Type: interventional
• Target: 711
• Locations: 8 countries
• Sites: 75

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).

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• The Change From Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Total Score to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

  The ALSFRS-R is used to measure the progression and severity of disease; it consists of 12 questions, assessing a patient's capability and independence in functional activities relevant to ALS, categorized in 4 domains: gross motor tasks, fine motor tasks, bulbar functions, and respiratory function. Each question is scored from 0 (indicating incapable or dependent) to 4 (normal). The total score ranges from 0 to 48, with higher scores reflecting more normal function and lower scores reflecting more impaired function.

  Baseline, 8 weeks, 12 weeks

Secondary Outcomes (6)

• Change From Baseline in Maximum Voluntary Ventilation (MVV) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

  Baseline, 8 weeks, 12 weeks

• Change From Baseline in Sniff Nasal Inspiratory Pressure (SNIP) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

  Baseline, 8 weeks, 12 weeks

• Change From Baseline in Slow Vital Capacity (SVC) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

  Baseline, 8 weeks, 12 weeks

• Change From Baseline in Maximum Handgrip Strength in the Weaker Hand to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

  Baseline, 8 weeks, 12 weeks

• Change From Baseline in Handgrip Fatigability (at 60% of Target in the Weaker Hand) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment

  Baseline, 8 weeks, 12 weeks

Study Arms (2)

CK-2017357

EXPERIMENTAL

125 mg tablets

Drug: CK-2017357; Drug: Riluzole

Placebo

PLACEBO COMPARATOR

Placebo tablets

Other: Placebo tablets; Drug: Riluzole

Interventions

CK-2017357 DRUG

CK-2017357 125 mg tablets twice daily

Also known as: tirasemtiv

CK-2017357

Placebo tablets OTHER

Tablets

Placebo

Riluzole DRUG

Tablets

Also known as: Rilutek

CK-2017357; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to comprehend and willing to sign an Informed Consent Form (ICF)
• Male or female 18 years of age or older
• 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)
• Upright Slow Vital Capacity (SVC) \>50 % of predicted for age, height and sex
• At least 4 of the 12 ALSFRS-R questions must be scored 2 or 3
• 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)
• Able to swallow tablets without crushing
• A caregiver (if one is needed) who can and will observe and report the patient's status
• Pre-study clinical laboratory findings within normal range or, if outside of the normal range, deemed not clinically significant by the Investigator
• 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
• 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
• 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.

You may not qualify if:

• 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
• Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS placement during the course of the study
• Body Mass Index (BMI) of 19.0 kg/m2 or lower
• Unwilling to discontinue tizanidine and theophylline-containing medications during study participation
• Serum chloride \< 100 mmol/L
• Neurological impairment due to a condition other than ALS, including history of transient ischemic attack (TIA) within the past year
• 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
• Has taken any investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
• Previously received CK-2017357 in any previous clinical trial

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (75)

Barrow Neurology

Phoenix, Arizona, 85013, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

UC Irvine ALS & Neuromuscular Center

Orange, California, 92868, United States

Location

Coordinated Clinical Research

San Diego, California, 92103, United States

Location

California Pacific Medical Center Forbes Norris MDA/ALS Research Center

San Francisco, California, 94115, United States

Location

Hospital for Special Care

New Britain, Connecticut, 06053, United States

Location

The George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Mayo Clinic Florida Department of Neurology

Jacksonville, Florida, 32224, United States

Location

Emory University, School of Medicine

Atlanta, Georgia, 30322, United States

Location

Georgia Health Sciences University

Augusta, Georgia, 30912, United States

Location

Indiana University Department of Neurology

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

St Mary's Healthcare

Grand Rapids, Michigan, 49503, United States

Location

Hennepin County Medical Center - Berman Center for Research

Minneapolis, Minnesota, 55415, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Neurology Associates

Lincoln, Nebraska, 68506, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13120, United States

Location

Carolinas Medical Center Department of Neurology

Charlotte, North Carolina, 27406, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Wake Forest University, School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Department of Neurology

Columbus, Ohio, 43221, United States

Location

Providence ALS Center

Portland, Oregon, 97213, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Penn State Hershey Neuroscience Clinics

Hershey, Pennsylvania, 17033, United States

Location

Drexel Neurology

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Neurology

Dallas, Texas, 75214, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

UTHSCSA Department of Neurology

San Antonio, Texas, 78229, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

West Virginia University Department of Neurology

Morgantown, West Virginia, 26506, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Heritage Medical Research

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, B3H 3A7, Canada

Location

University of British Columbia

Vancouver, British Columbia, V5Z 2G9, Canada

Location

Stan Cassidy Centre for Rehabilitation

Fredericton, New Brunswick, E3B 0C7, Canada

Location

QE II Health Sciences Centre

Halifax, Nova Scotia, B3H 3A7, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8S 4K1, Canada

Location

Queen's University : Kingston General

Kingston, Ontario, K7L 2V7, Canada

Location

London Health Sciences

London, Ontario, N6A 5A5, Canada

Location

Univ. of Toronto - Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

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

Montreal, Quebec, H2L4M1, Canada

Location

Montreal Neurological Institute

Montreal, Quebec, H3A 2B4, Canada

Location

CHU de Quebec: Hopital l'Enfant-Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

CHRU de Lille - Hôpital Roger Salengro

Lille, F-59037 LILLE cedex, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, 87042 LIMOGES CEDEX, France

Location

Hôpital La Timone Adulte

Marseille, 13005, France

Location

CHU Montepellier

Montpellier, 34295 Montpellier Cedex 5, France

Location

Hôpital Archet 1

Nice, 06602, France

Location

Hôpital de la Salpêtrière

Paris, Cedex 13, France

Location

Hôpital Bretonneau

Tours, 37000, France

Location

Charite Universitätsmedizin

Berlin, 13353, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

University of Ulm

Ulm, 89081, Germany

Location

Trinity College, Beaumont Hospital

Dublin, 9, Ireland

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital Carlos III

Madrid, 28029, Spain

Location

Barts and the London MND & the Centre Royal London Hospital

Whitechapel, London, United Kingdom

Location

Walton Centre for Neurology and Neurosurgery

Liverpool, L9 7LJ, United Kingdom

Location

Kings College Hospital NHS Foundation Trust

London, SE5 8AF, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Sheffield Institute for Translational Neuroscience

Sheffield, S10 2HQ, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

CK-2017357; Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: MD Cytokinetics
• Organization: Cytokinetics, Inc.

medicalaffairs@cytokinetics.com

650-624-2929

Study Officials

• Jinsy Andrews, MD

  Cytokinetics, Inc.

  STUDY DIRECTOR

• Jeremy Shefner, MD, PhD

  State University of New York - Upstate Medical University

  STUDY CHAIR

• Jeremy Shefner, MD, PhD

  State University of New York - Upstate Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 18, 2012
• Study Start: October 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: March 31, 2020
• Results First Posted: March 31, 2020

Record last verified: 2020-03

Locations

FR (7); US (44); DE (3); CA (12); IE (1); GB (6); NL (1); ES (1)