Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
VITALITY-ALS
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)
2 other identifiers
interventional
744
11 countries
81
Brief Summary
This study assessed the effect of tirasemtiv versus placebo on respiratory function in patients with ALS.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2015
81 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 10, 2015
CompletedFirst Posted
Study publicly available on registry
July 14, 2015
CompletedStudy Start
First participant enrolled
September 3, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 9, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 27, 2017
CompletedResults Posted
Study results publicly available
June 19, 2020
CompletedSeptember 9, 2020
August 1, 2020
1.5 years
July 10, 2015
May 6, 2020
August 21, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline to Week 24 of the Double-blind, Placebo-controlled Phase in Percent Predicted Slow Vital Capacity (SVC)
SVC was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, the patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs). Values obtained were converted to % predicted values (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics \[eg, height, age, sex\], based on Knudson 83 normative values).
24 weeks
Secondary Outcomes (6)
Change From Baseline in the ALSFRS-R Respiratory Domain Score at the End of 48 Weeks of Double-blind, Placebo-controlled Treatment
48 weeks
Slope of Mega-score of Muscle Strength During the 48 Weeks of Double-blind, Placebo-controlled Treatment
48 weeks
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 All 48 Weeks of Double-blind, Placebo-controlled Treatment
48 weeks
Time to the First Occurrence of a Decline in SVC to ≤ 50% Predicted, or the Onset of Respiratory Insufficiency, or Death During the 48 Weeks of Double-blind, Placebo-controlled Treatment
48 weeks
Change From Baseline in the ALSFRS-R Total Score to the End of 48 Weeks of the Double-blind, Placebo-controlled Treatment
48 weeks
- +1 more secondary outcomes
Study Arms (4)
Group 1 - Placebo
PLACEBO COMPARATORDay 1 through Week 48: 2 placebo tablets twice daily
Group 2 - 250 mg tirasemtiv
EXPERIMENTALDay 1 through Week 48: 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in the AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in the PM
Group 3 - 375 mg tirasemtiv
EXPERIMENTALDay 1 through Week 2: 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in the AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in the PM; Weeks 3 through 48: 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in the AM and 2 tablets of tirasemtiv (250 mg) in the PM
Group 4 - 500 mg tirasemtiv
EXPERIMENTALDay 1 through Week 2: 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in the AM and 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in PM; Weeks 3 and 4: 1 tablet of tirasemtiv (125 mg) and 1 tablet of matching placebo in the AM and 2 tablets of tirasemtiv (250 mg) in the PM; Weeks 5 through 48: 2 tablets of tirasemtiv (250 mg) in the AM and 2 tablets of tirasemtiv (250 mg) in the PM
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cytokineticslead
Study Sites (81)
St. Joseph's Hospital & Medical Center - Barrow Neurology Clinics
Phoenix, Arizona, 85013, United States
University of California San Diego
La Jolla, California, 92093, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
University of California, Irvine
Orange, California, 92868, United States
University of California Davis Medical Center
Sacramento, California, 95817, United States
Forbes Norris MDA/ALS Research Center
San Francisco, California, 94115, United States
Stanford Hospital and Clinics
Stanford, California, 94305, United States
University of Colorado Hospital Anschutz Outpatient Pavilion
Aurora, Colorado, 80045, United States
Hospital for Special Care
New Britain, Connecticut, 06053, United States
George Washington University Medical Center
Washington D.C., District of Columbia, 20037, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
University of Miami
Miami, Florida, 33136, United States
Carol and Frank Morsini Center for Advanced Health Care - University of South Florida
Tampa, Florida, 33612, United States
The Emory Clinic
Atlanta, Georgia, 30322, United States
Georgia Regents University
Augusta, Georgia, 30912, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Indiana University
Indianapolis, Indiana, 46202, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655, United States
University of Michigan Hospital and Health System
Ann Arbor, Michigan, 48109, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
Saint Louis University
St Louis, Missouri, 63104, United States
Barnes-Jewish Hospital
St Louis, Missouri, 63110, United States
Neurology Associates
Lincoln, Nebraska, 68506, United States
Dartmouth Hitchcock Medical Center Dept of Neurology
Lebanon, New Hampshire, 03756, United States
Hospital for Special Surgery
New York, New York, 10021, United States
Neurological Institute Columbia University Medical Center
New York, New York, 10032, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Neurosciences Institute: Neurology - Charlotte
Charlotte, North Carolina, 28207, United States
Duke Neurological Disorders Clinic
Durham, North Carolina, 27705, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43221, United States
Providence Brain and Spine Institute ALS Center
Portland, Oregon, 97213, United States
Oregon Health and Science Center
Portland, Oregon, 97239, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
The Penn Comprehensive Neuroscience Center
Philadelphia, Pennsylvania, 19107, United States
Temple University School of Medicine
Philadelphia, Pennsylvania, 19140, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Texas Neurology
Dallas, Texas, 75214, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
University of Texas Health Science Center
San Antonio, Texas, 78229, United States
University of Virgina Health System
Charlottesville, Virginia, 22908, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
West Virginia University Department of Neurology
Morgantown, West Virginia, 26506, United States
Froedtert Memorial Lutheran Hospital, Department of Neurology
Milwaukee, Wisconsin, 53226, United States
UZ Leuven - Campus Gasthuisberg
Leuven, Vlaams Brabant, 3000, Belgium
University of Calgary
Calgary, Alberta, T3M 1M4, Canada
Edmonton Kaye Clinic
Edmonton, Alberta, T6G 1Z1, Canada
Stan Cassidy Centre for Rehabilitation
Fredericton, New Brunswick, E3B OC7, Canada
QE II Health Sciences Centre, NHI Site
Halifax, Nova Scotia, B3H 1V7, Canada
McMaster University Medical Centre
Hamilton, Ontario, L8N 4K1, Canada
London Health Sciences Centre
London, Ontario, N6A 5A5, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Notre-Dame Hospital/CHUM
Montreal, Quebec, H2L 4M1, Canada
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4, Canada
CHU de Quebec - Universite Laval Hopital de l'Enfant-Jesus
Québec, G1J 1Z4, Canada
Hopital R. Salengro, CHRU Lille
Lille, 59037, France
CHU Dupuytren
Limoges, 87042, France
Hopital de la Timone
Marseille, 13005, France
Hopital Gui de Chauliac
Montpellier, 34295, France
CHU de Nice - Hopital Pasteur 2
Nice, 06001, France
Hopital de la Salpetriere
Paris, 75651, France
Bretonneau University Hospital
Tours, 37044, France
University of Ulm, Department of Neurology
Ulm, Baden-Wurttemberg, 89081, Germany
Hannover Medical School, Department of Neurology
Hanover, Lower Saxony, 30625, Germany
Charite Campus Virchow-Klinikum, Neurology Department
Berlin, 13353, Germany
Clinical Research Centre, Beaumont Hospital
Dublin, Dublin 9, Ireland
IRCCS Istituto Auxologico Italiano - U.O. Neurologia
Milan, 20149, Italy
Centro Clinico NEMO - Fondazione Serena Onlus, ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162, Italy
Dipartimento di Neuroscienze "Rita Levi Moltalcini" A.O.U. Citta della Salute e della Scienza di Torino P.O. "Molinette"
Torino, 10126, Italy
University Medical Center Utrecht
Utrecht, 3584 CX, Netherlands
Hospital Santa Maria-Centro Hospitalar Lisboa Norte
Lisbon, 1649-035, Portugal
Hospital San Rafael
Madrid, 28016, Spain
Derriford Hospital
Plymouth, Devon, PL6 8DH, United Kingdom
Walton Centre for Neurology and Neurosurgery
Liverpool, L9 7LJ, United Kingdom
Clinical Research Centre, Royal London Hospital
London, E1 2AT, United Kingdom
Kings College Hospital
London, SE59RS, United Kingdom
Related Publications (2)
Simkins TJ, Kupfer S, Malik FI, Meng L, Rudnicki SA, Wei J, Shefner JM, Bowser R. Plasma neurofilament analysis in VITALITY-ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2025 Feb;26(1-2):103-112. doi: 10.1080/21678421.2024.2423707. Epub 2024 Nov 8.
PMID: 39513379DERIVEDAndrews JA, Cudkowicz ME, Hardiman O, Meng L, Bian A, Lee J, Wolff AA, Malik FI, Shefner JM. VITALITY-ALS, a phase III trial of tirasemtiv, a selective fast skeletal muscle troponin activator, as a potential treatment for patients with amyotrophic lateral sclerosis: study design and baseline characteristics. Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3-4):259-266. doi: 10.1080/21678421.2018.1426770. Epub 2018 Feb 6.
PMID: 29402141DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- MD Cytokinetics
- Organization
- Cytokinetics, Inc.
Study Officials
- STUDY DIRECTOR
MD
Cytokinetics
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 10, 2015
First Posted
July 14, 2015
Study Start
September 3, 2015
Primary Completion
March 9, 2017
Study Completion
September 27, 2017
Last Updated
September 9, 2020
Results First Posted
June 19, 2020
Record last verified: 2020-08