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Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year (VITALITY-ALS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Cytokinetics
ClinicalTrials.gov Identifier:
NCT02496767
First received: July 10, 2015
Last updated: January 6, 2017
Last verified: January 2017
  Purpose
This study is to assess the effect of tirasemtiv versus placebo on respiratory function in patients with ALS.

Condition Intervention Phase
Amyotrophic Lateral Sclerosis Drug: tirasemtiv Drug: Placebo tablets Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multi-National, Double-Blind, Randomized, Placebo-Controlled, Stratified, Parallel Group, Study to Evaluate the Safety, Tolerability and Efficacy of Tirasemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Change from baseline to Week 24 of the double-blind, placebo-controlled phase in percent predicted slow vital capacity (SVC) [ Time Frame: 24 weeks ]

Secondary Outcome Measures:
  • Time to the first occurrence of a decline from baseline in percent predicted SVC ≥ 20 percentage points or the onset of respiratory insufficiency or death during double-blind, placebo-controlled treatment [ Time Frame: 48 weeks ]
  • Time to the first occurrence of a decline in SVC to ≤ 50% predicted or the onset of respiratory insufficiency or death during double-blind, placebo-controlled treatment [ Time Frame: 48 weeks ]
  • Time to the first occurrence of the first use of mechanical ventilatory assistance or death during double-blind, placebo-controlled treatment [ Time Frame: 48 weeks ]
  • Time to the first occurrence of a decline in the respiratory components of the ALSFRS-R (i.e., items 10, 11, and 12) or death during double-blind, placebo-controlled treatment [ Time Frame: 48 weeks ]
  • Slope in muscle strength mega-score change from baseline during the randomized, double-blind, placebo-controlled phase [ Time Frame: 24 weeks ]

Enrollment: 743
Study Start Date: August 2015
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group 1 - Placebo
Day 1 through Week 48 - 2 placebo tablets twice daily
Drug: Placebo tablets
Experimental: Group 2 - 250 mg tirasemtiv
Day 1 through Week 48 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in PM
Drug: tirasemtiv
Other Name: CK-2017357
Drug: Placebo tablets
Experimental: Group 3 - 375 mg tirasemtiv
Day 1 through Week 2 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in PM; Weeks 3 through 48 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 2 tablets of tirasemtiv (250 mg) in PM
Drug: tirasemtiv
Other Name: CK-2017357
Drug: Placebo tablets
Experimental: Group 4 - 500 mg tirasemtiv
Day 1 through Week 2 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in PM; Weeks 3 and 4 - 1 tablet (125 mg) of tirasemtiv and 1 tablet of matching placebo in AM and 2 tablets of tirasemtiv (250 mg) in PM; Weeks 5 through 48 - 2 tablets (250 mg) of tirasemtiv in AM and 2 tablets of tirasemtiv (250 mg) in PM
Drug: tirasemtiv
Other Name: CK-2017357
Drug: Placebo tablets

Detailed Description:
CY 4031 is a multi-national, double-blind, randomized, placebo-controlled, stratified, parallel group study in patients with ALS with the selective fast skeletal muscle troponin activator, tirasemtiv. The study includes three phases; an open-label phase (2 weeks), a double-blind, placebo-controlled phase (48 weeks), and a double-blind, placebo-controlled tirasemtiv withdrawal phase (4 weeks). Patients who can complete two weeks of treatment with open-label tirasemtiv (125 mg twice daily) will be randomized 3:2:2:2 to placebo and three different dose levels of tirasemtiv. Approximately 600 patients will be enrolled onto open-label treatment. Patients who enter the study on riluzole 50 mg twice daily will continue on riluzole but at a reduced dose of 50 mg once daily.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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) ≤ 24 months prior to screening
  • Upright SVC ≥ 70 % of predicted for age, height and sex
  • Able to swallow tablets without crushing, and in the opinion of the Investigator, is expected to continue to be able to do so during the trial
  • A caregiver if one is needed
  • Clinical laboratory findings within the normal range or, if outside 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 childbearing potential (i.e., following menarche until post-menopausal if not anatomically and physiologically incapable of becoming pregnant) 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, unless the male patient has had a vasectomy and confirmed sperm count is zero
  • 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 effective contraceptive drugs or devices while requiring male partner to use a condom 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 until they complete study drug dosing

Exclusion Criteria:

  • At the time of screening, any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous positive airway pressure [CPAP] or bi-level 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
  • BMI of 20.0 kg/m2 or lower
  • Unwilling or unable to discontinue tizanidine and theophylline-containing medications during study participation
  • Serum chloride outside the normal reference range
  • Neurological impairment due to a condition other than ALS, including history of transient ischemic attack within the past year
  • Presence at screening of any medically significant cardiac, pulmonary, 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, including, but not limited to:

    1. Poorly controlled hypertension
    2. NYHA Class II or greater congestive heart failure
    3. Chronic obstructive pulmonary disease or asthma requiring daily use bronchodilator medications
    4. GI disorder that might impair absorption of study drug
    5. History of significant liver disease defined by bilirubin > 2 times the upper limit of normal (ULN) or ALT or AST > 3 times the ULN on repeat testing
    6. Poorly controlled diabetes mellitus
    7. History of vertigo within three months of study entry
    8. History of syncope without an explainable or treated cause
    9. History of untreated intracranial aneurysm or poorly controlled seizure disorder
    10. Amputation of a limb
    11. Cognitive impairment, related to ALS or otherwise, sufficient to impair the patient's ability to give informed consent and to understand and/or comply with study procedures
    12. Cancer with metastatic potential (other than basal cell carcinoma, carcinoma in situ of the cervix, or squamous cell carcinoma of the skin excised with clean margins) diagnosed and treated within the last two years
    13. Any other condition, impairment or social circumstance that, in the opinion of the Investigator, would render the patient not suitable to participate in the study
    14. Patient judged to be actively suicidal or a suicide risk by the Investigator
  • Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is greater, prior to dosing
  • Prior participation in any form of stem cell therapy for the treatment of ALS
  • Previously received tirasemtiv in any previous clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02496767

  Hide Study Locations
Locations
United States, Arizona
St. Joseph's Hospital & Medical Center - Barrow Neurology Clinics
Phoenix, Arizona, United States, 85013
United States, California
University of California San Diego
La Jolla, California, United States, 92093
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
University of California, Irvine
Orange, California, United States, 92868
University of California Davis Medical Center
Sacramento, California, United States, 95817
Forbes Norris MDA/ALS Research Center
San Francisco, California, United States, 94115
Stanford Hospital and Clinics
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Hospital Anschutz Outpatient Pavilion
Aurora, Colorado, United States, 80045
United States, Connecticut
Hospital for Special Care
New Britain, Connecticut, United States, 06053
United States, District of Columbia
George Washington University Medical Center
Washington, District of Columbia, United States, 20037
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
University of Miami
Miami, Florida, United States, 33136
Carol and Frank Morsini Center for Advanced Health Care - University of South Florida
Tampa, Florida, United States, 33612
United States, Georgia
The Emory Clinic
Atlanta, Georgia, United States, 30322
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University
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 Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, Michigan
University of Michigan Hospital and Health System
Ann Arbor, Michigan, United States, 48109
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63104
Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Nebraska
Neurology Associates
Lincoln, Nebraska, United States, 68506
United States, New Hampshire
Dartmouth Hitchcock Medical Center Dept of Neurology
Lebanon, New Hampshire, United States, 03756
United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
Neurological Institute Columbia University Medical Center
New York, New York, United States, 10032
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
Neurosciences Institute: Neurology - Charlotte
Charlotte, North Carolina, United States, 28207
Duke Neurological Disorders Clinic
Durham, North Carolina, United States, 27705
Wake Forest University Health Sciences
Winston Salem, North Carolina, United States, 27157
United States, Ohio
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43221
United States, Oregon
Providence Brain and Spine Institute ALS Center
Portland, Oregon, United States, 97213
Oregon Health and Science Center
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
The Penn Comprehensive Neuroscience Center
Philadelphia, Pennsylvania, United States, 19107
Temple University School of Medicine
Philadelphia, Pennsylvania, United States, 19140
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
University of Texas Health Science Center
San Antonio, Texas, United States, 78229
United States, Virginia
University of Virgina Health System
Charlottesville, Virginia, United States, 22908
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
United States, West Virginia
West Virginia University Department of Neurology
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Froedtert Memorial Lutheran Hospital, Department of Neurology
Milwaukee, Wisconsin, United States, 53226
Belgium
UZ Leuven - Campus Gasthuisberg
Leuven, Vlaams Brabant, Belgium, 3000
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T3M 1M4
Edmonton Kaye Clinic
Edmonton, Alberta, Canada, T6G 1Z1
Canada, New Brunswick
Stan Cassidy Centre for Rehabilitation
Fredericton, New Brunswick, Canada, E3B OC7
Canada, Nova Scotia
QE II Health Sciences Centre, NHI Site
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
McMaster University Medical Centre
Hamilton, Ontario, Canada, L8N 4K1
London Health Sciences Centre
London, Ontario, Canada, N6A 5A5
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Notre-Dame Hospital/CHUM
Montreal, Quebec, Canada, H2L 4M1
Montreal Neurological Institute and Hospital
Montreal, Quebec, Canada, H3A 2B4
Canada
CHU de Quebec - Universite Laval Hopital de l'Enfant-Jesus
Quebec, Canada, G1J 1Z4
France
Hopital R. Salengro, CHRU Lille
Lille Cedex, France, 59037
CHU Dupuytren
Limoges cedex, France, 87042
Hopital de la Timone
Marseille, France, 13005
Hopital Gui de Chauliac
Montpellier, France, 34295
CHU de Nice - Hopital Pasteur 2
Nice Cedex 1, France, 06001
Hopital de la Salpetriere
Paris, France, 75651
Bretonneau University Hospital
Tours Cedex 9, France, 37044
Germany
University of Ulm, Department of Neurology
Ulm, Baden-Wuerttemberg, Germany, 89081
Hannover Medical School, Department of Neurology
Hannover, Lower Saxony, Germany, 30625
Charite Campus Virchow-Klinikum, Neurology Department
Berlin, Germany, 13353
Ireland
Clinical Research Centre, Beaumont Hospital
Dublin, Ireland, Dublin 9
Italy
IRCCS Istituto Auxologico Italiano - U.O. Neurologia
Milan, Italy, 20149
Centro Clinico NEMO - Fondazione Serena Onlus, ASST Grande Ospedale Metropolitano Niguarda
Milan, Italy, 20162
Dipartimento di Neuroscienze "Rita Levi Moltalcini" A.O.U. Citta della Salute e della Scienza di Torino P.O. "Molinette"
Torino, Italy, 10126
Netherlands
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Portugal
Hospital Santa Maria-Centro Hospitalar Lisboa Norte
Lisboa, Portugal, 1649-035
Spain
Hospital San Rafael
Madrid, Spain, 28016
United Kingdom
Derriford Hospital
Plymouth, Devon, United Kingdom, PL6 8DH
Walton Centre for Neurology and Neurosurgery
Liverpool, United Kingdom, L9 7LJ
Clinical Research Centre, Royal London Hospital
London, United Kingdom, E1 2AT
Kings College Hospital
London, United Kingdom, SE59RS
Sponsors and Collaborators
Cytokinetics
Investigators
Study Director: MD Cytokinetics
  More Information

Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT02496767     History of Changes
Other Study ID Numbers: CY 4031
2014-005413-23 ( EudraCT Number )
Study First Received: July 10, 2015
Last Updated: January 6, 2017

Keywords provided by Cytokinetics:
fast skeletal troponin activator
tirasemtiv
CK-2017357
double-blind
randomized
placebo-controlled

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

ClinicalTrials.gov processed this record on June 23, 2017