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 (VITALITY-ALS)

Study Purpose:

This study is to assess the effect of tirasemtiv versus placebo on respiratory function in patients with ALS.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Active, no longer recruiting

Phase:

Phase III

Study Chair(s)/Principal Investigator(s):

Study Director: MD Cytokinetics

Clinicaltrials.gov ID (11 digit #):

NCT02496767

Neals Affiliated?

Yes

Coordinating Center Contact Information

MD Cytokinetics
Sarah Kulke, MD / .(JavaScript must be enabled to view this email address)
.(JavaScript must be enabled to view this email address) United States

Full Study Summary:

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 445 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.

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
-Time to the first occurrence of a decline in the respiratory components of the ALS functional rating scale- revised (ALSFRS-R) (i.e., items 10, 11, and 12) or death during double-blind, placebo-controlled treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
-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 ] [ Designated as safety issue: No ]
-Time to the first occurrence of any use of assisted ventilation or death during double-blind, placebo-controlled treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
-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 ] [ Designated as safety issue: No ]
-Slope in muscle strength mega-score change from baseline during the randomized, double-blind, placebo-controlled phase [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Study Sponsor:

Cytokinetics

Participant Duration:

Estimated Enrollment:

600

Estimated Study Start Date:

07/31/2015

Estimated Study Completion Date:

07/31/2017

Posting Last Modified Date:

05/08/2017

Date Study Added to alsconsortium.org:

07/14/2015
  • More Information

    Alternative study name: Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year (VITALITY-ALS).
    For more information, please visit https://clinicalt...CT02496767&rank=1

  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Min Vital Capacity (% predicted normal):

    70

    Time since Symptom Onset:

    Time since Diagnosis:

    <24

    Can participants use Riluzole?

    Yes


    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 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 8 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:
    -Poorly controlled hypertension
    -NYHA Class II or greater congestive heart failure
    -Chronic obstructive pulmonary disease or asthma requiring daily use bronchodilator medications
    -GI disorder that might impair absorption of study drug
    -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
    -Poorly controlled diabetes mellitus
    -History of vertigo within three months of study entry
    -History of syncope without an explainable or treated cause
    -History of untreated intracranial aneurysm or poorly controlled seizure disorder
    -Amputation of a limb
    -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
    -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
    -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
    -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

  • Site Contact Information

    Barrow Neurological Institute
    St. Joseph's Hospital & Medical Center
    Phoenix, Arizona 85013
    United States

    Baylor College of Medicine
    Houston, Texas 77030
    United States

    Cedars-Sinai Medical Center
    Los Angeles, California 90048
    United States

    Columbia University Medical Center
    Neurological Institute
    New York, New York 10032
    United States

    Dartmouth Hitchcock Medical Center
    Dept of Neurology
    Lebanon, New Hampshire 03756
    United States

    Drexel University College of Medicine
    Philadelphia, Pennsylvania 19107
    United States

    Duke University School of Medicine
    Neurological Disorders Clinic
    Durham, North Carolina 27705
    United States

    Forbes Norris MDA/ALS Research Center
    San Francisco, California 94115
    United States

    George Washington University Medical Center
    Washington, Washington D.C. 20037
    United States

    Georgia Regents University
    Augusta, Georgia 30912
    United States

    Hennepin County Medical Center
    Twin Cities ALS Research Consortium
    Minneapolis, Minnesota 55415
    United States

    Henry Ford Health System
    Detroit, Michigan 48202
    United States

    Hospital for Special Care
    New Britain, Connecticut 06053
    United States

    Hospital for Special Surgery
    New York, New York 10021
    United States

    Indiana University
    Indianapolis, Indiana 46202
    United States

    Johns Hopkins University
    Baltimore, Maryland 21287
    United States

    Massachusetts General Hospital
    Boston, Massachusetts 02114
    United States

    Mayo Clinic, Jacksonville
    Jacksonville, Florida 32224
    United States

    Medical College of Wisconsin
    Froedtert Memorial Lutheran Hospital
    Milwaukee, Wisconsin 53226
    United States

    Neurology Associates
    Lincoln, Nebraska 68506
    United States

    Neurosciences Institute
    Department of Neurology
    Charlotte, North Carolina 28207
    United States

    Northwestern University
    Feinberg School of Medicine
    Chicago, Illinois 60611
    United States

    Ohio State University
    Wexner Medical Center
    Columbus, Ohio 43221
    United States

    Penn State
    Milton S. Hershey Medical Center
    Hershey, Pennsylvania 17033
    United States

    Providence Brain and Spine Institute ALS Center
    Portland, Oregon 97213
    United States

    Saint Louis University
    St. Louis, Missouri 63104
    United States

    Stanford Hospitals and Clinics
    Stanford, California 94305
    United States

    SUNY Upstate Medical University
    Syracuse, New York 13210
    United States

    Texas Neurology
    Dallas, Texas 75214
    United States

    The Emory Clinic
    Atlanta, Georgia 30322
    United States

    The Penn Comprehensive Neuroscience Center
    Philadelphia, Pennsylvania 19107
    United States

    University of California Davis Medical Center
    Sacramento, California 95817
    United States

    University of California San Diego
    La Jolla, California 92093
    United States

    University of California, Irvine
    Orange, California 92868
    United States

    University of Colorado Hospital
    Anschutz Outpatient Pavilion
    Aurora, Colorado 80045
    United States

    University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242
    United States

    University of Kansas Medical Center
    3599 Rainbow Blvd.
    Kansas City, Kansas 66160
    United States

    University of Massachusetts Memorial Medical Center
    Worcester, Massachusetts 01655
    United States

    University of Miami
    Miami, Florida 33136
    United States

    University of Michigan Hospital
    Ann Arbor, Michigan 48109
    United States

    University of South Florida
    Carol and Frank Morsini Center for Advanced Health Care
    Tampa, Florida 33612
    United States

    University of Texas Health Science Center
    San Antonio, Texas 78229
    United States

    University of Virgina
    Charlottesville, Virginia 22908
    United States

    University of Washington Medical Center
    Seattle, Washington 98195
    United States

    Vanderbilt University Medical Center
    Nashville, Tennessee 37232
    United States

    Wake Forest University Health Sciences
    Winston Salem, North Carolina 27157
    United States

    Washington University
    Barnes-Jewish Hospital
    St. Louis, Missouri 63110
    United States

    West Virginia University
    Department of Neurology
    Morgantown, West Virginia 26506
    United States

    UZ Leuven - Campus Gasthuisberg
    Leuven, Vlaams Brabant 3000
    Belgium

    Stan Cassidy Centre for Rehabilitation
    Fredericton, New Brunswick E3B OC7
    Canada

    QE II Health Sciences Centre
    Halifax, Nova Scotia B3H 3A7
    Canada

    London Health Sciences Centre
    London, Ontario N6A 5A5
    Canada

    Edmonton Kaye Clinic
    Edmonton, Alberta T6G 1Z1
    Canada

    Notre-Dame Hospital/CHUM
    Montreal, Quebec H2L 4M1
    Canada

    CHU de Quebec - Universite Laval Hopital de l'Enfant-Jesus
    Quebec, Quebec G1J 1Z4
    Canada

    University of Toronto
    Sunnybrook Health Sciences Centre
    Toronto, Ontario M4N 3M5
    Canada

    McMaster University Medical Centre
    Hamilton, Ontario L8N 4K1
    Canada

    University of Calgary
    Calgary, Alberta T3M 1M4
    Canada

    Montreal Neurological Institute and Hospital
    McGill University
    Montreal, Quebec H3A 2B4
    Canada

    Hospital San Rafael
    Madrid, 28016
    Spain

    Bretonneau University Hospital
    Tours Cedex 9, 37044
    France

    Hopital Gui de Chauliac
    Montpellier, 34295
    France

    CHU Dupuytren
    Limoges cedex, 87042
    France

    Royal London Hospital
    Clinical Research Centre
    London, E1 2AT
    United Kingdom

    Kings College Hospital
    London, SE59RS
    United Kingdom

    Derriford Hospital
    Plymouth, Devon PL6 8DH
    United Kingdom

    Walton Centre for Neurology and Neurosurgery
    Liverpool, L9 7LJ
    United Kingdom

    Clinical Research Centre, Beaumont Hospital
    Dublin, Co. Dublin Dublin 9
    Ireland

    University Medical Center Utrecht
    Utrecht, 3584 CX
    Netherlands