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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cytokinetics
ClinicalTrials.gov Identifier:
NCT01709149
First received: October 16, 2012
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: CK-2017357
Other: Placebo tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIb, Multi-National, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Efficacy of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS) (BENEFIT-ALS)

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • The change from baseline to the average of the ALS Functional Rating Scale-Revised (ALSFRS-R) total score obtained at Visits 6 and 7 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Maximum Voluntary Ventilation (MVV) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in Sniff Nasal Inspiratory Pressure (SNIP) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in Slow Vital Capacity (SVC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in handgrip strength and fatigability [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    As measured by maximum handgrip strength and sub-maximum handgrip strength

  • Change in muscle strength by hand-held dynamometry (HHD) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    As determined by the megascore of:

    Elbow flexion (bilateral), wrist extension (bilateral), knee extension (bilateral), and ankle dorsiflexion (bilateral)



Estimated Enrollment: 680
Study Start Date: October 2012
Study Completion Date: March 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CK-2017357
125 mg tablets
Drug: CK-2017357
Other Name: tirasemtiv
Placebo Comparator: Placebo
Placebo tablets
Other: Placebo tablets

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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) >60 % 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 40 pounds (females) and 10 and 60 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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01709149

  Hide Study Locations
Locations
United States, Arizona
Barrow Neurology
Phoenix, Arizona, United States, 85013
United States, California
University of California, San Diego
La Jolla, California, United States, 92093
UC Irvine ALS & Neuromuscular Center
Orange, California, United States, 92868
Coordinated Clinical Research
San Diego, California, United States, 92103
California Pacific Medical Center Forbes Norris MDA/ALS Research Center
San Francisco, California, United States, 94115
United States, Connecticut
Hospital for Special Care
New Britain, Connecticut, United States, 06053
United States, District of Columbia
The George Washington University
Washington, District of Columbia, United States, 20037
United States, Florida
Mayo Clinic Florida Department of Neurology
Jacksonville, Florida, United States, 32224
United States, Georgia
Emory University, School of Medicine
Atlanta, Georgia, United States, 30322
Georgia Health Sciences University
Augusta, Georgia, United States, 30912
United States, Indiana
Indiana University Department of Neurology
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Henry Ford Hospital
Detroit, Michigan, United States, 48202
St Mary's Healthcare
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Hennepin County Medical Center - Berman Center for Research
Minneapolis, Minnesota, United States, 55415
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
Saint Louis University
St. Louis, Missouri, United States, 63104
United States, Nebraska
Neurology Associates
Lincoln, Nebraska, United States, 68506
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
University of Rochester
Rochester, New York, United States, 14642
SUNY Upstate Medical University
Syracuse, New York, United States, 13120
United States, North Carolina
Carolinas Medical Center Department of Neurology
Charlotte, North Carolina, United States, 27406
Duke University
Durham, North Carolina, United States, 27705
Wake Forest University, School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Ohio State University Department of Neurology
Columbus, Ohio, United States, 43221
United States, Oregon
Providence ALS Center
Portand, Oregon, United States, 97213
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Hershey Neuroscience Clinics
Hershey, Pennsylvania, United States, 17033
Drexel Neurology
Philadelphia, Pennsylvania, United States, 19107
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Neurology
Dallas, Texas, United States, 75214
Baylor College of Medicine
Houston, Texas, United States, 77030
UTHSCSA Department of Neurology
San Antonio, Texas, United States, 78229
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
United States, West Virginia
West Virginia University Department of Neurology
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Heritage Medical Research
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta Hospital
Edmonton, Alberta, Canada, B3H 3A7
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 2G9
Canada, New Brunswick
Stan Cassidy Centre for Rehabilitation
Fredericton, New Brunswick, Canada, E3B 0C7
Canada, Nova Scotia
QE II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
McMaster University Medical Centre
Hamilton, Ontario, Canada, L8S 4K1
Queen's University : Kingston General
Kingston, Ontario, Canada, K7L 2V7
London Health Sciences
London, Ontario, Canada, N6A 5A5
Univ. of Toronto - Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Montreal Neurological Institute
Montreal, Quebec, Canada, H3A 2B4
Hôpital Notre Dame (CHUM) Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada, H2L4M1
Canada
CHU de Quebec: Hopital l'Enfant-Jesus
Quebec, Canada, G1J 1Z4
France
CHRU de Lille - Hôpital Roger Salengro
Lille, France, F-59037 LILLE cedex
CHU de Limoges - Hôpital Dupuytren
Limoges, France, 87042 LIMOGES CEDEX
Hôpital La Timone Adulte
Marseille, France, 13005
CHU Montepellier
Montpellier, France, 34295 Montpellier Cedex 5
Hôpital Archet 1
Nice, France, 06602
Hôpital de la Salpêtrière
Paris, France, Cedex 13
Hôpital Bretonneau
Tours, France, 37000
Germany
Charite Universitätsmedizin
Berlin, Germany, 13353
Hannover Medical School
Hannover, Germany, 30625
University of Ulm
Ulm, Germany, 89081
Ireland
Trinity College, Beaumont Hospital
Dublin, Ireland, 9
Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584 CX
Spain
Hospital Carlos III
Madrid, Spain, 28029
United Kingdom
Barts and the London MND & the Centre Royal London Hospital
Whitechapel, London, United Kingdom
Walton Centre for Neurology and Neurosurgery
Liverpool, United Kingdom, L9 7LJ
Kings College Hospital NHS Foundation Trust
London, United Kingdom, SE5 8AF
John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
Plymouth Hospitals NHS Trust
Plymouth, United Kingdom, PL6 8DH
Sheffield Institute for Translational Neuroscience
Sheffield, United Kingdom, S10 2HQ
Sponsors and Collaborators
Cytokinetics
Investigators
Study Director: Jinsy Andrews, MD Cytokinetics, Inc.
Study Chair: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
Principal Investigator: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
  More Information

No publications provided

Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT01709149     History of Changes
Other Study ID Numbers: CY 4026
Study First Received: October 16, 2012
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 14, 2014