Amyotrophic Lateral SclerosisPhase 3VITALITY-ALSNCT02496767
Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
A Phase 3 study testing Tirasemtiv in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 81 sites in 11 countries.
Trial summary
This study assessed the effect of tirasemtiv versus placebo on respiratory function in patients with ALS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Tirasemtiv
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 744 participants
- Where
- 81 sitesin 11 countries
- Study dates
- 3 Sep 2015to 27 Sep 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
81 sites in 11 countries.
81 sites in 11 countries
United States49 sites
University of Michigan Hospital and Health System
Ann Arbor, Michigan, 48109
The Emory Clinic
Atlanta, Georgia, 30322
Georgia Regents University
Augusta, Georgia, 30912
University of Colorado Hospital Anschutz Outpatient Pavilion
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Neurosciences Institute: Neurology - Charlotte
Charlotte, North Carolina, 28207
University of Virgina Health System
Charlottesville, Virginia, 22908
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43221
Texas Neurology
Dallas, Texas, 75214
Henry Ford Health System
Detroit, Michigan, 48202
Duke Neurological Disorders Clinic
Durham, North Carolina, 27705
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Baylor College of Medicine
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Mayo Clinic
Jacksonville, Florida, 32224
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of California San Diego
La Jolla, California, 92093
Dartmouth Hitchcock Medical Center Dept of Neurology
Lebanon, New Hampshire, 03756
Neurology Associates
Lincoln, Nebraska, 68506
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Miami
Miami, Florida, 33136
Froedtert Memorial Lutheran Hospital, Department of Neurology
Milwaukee, Wisconsin, 53226
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
West Virginia University Department of Neurology
Morgantown, West Virginia, 26506
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Hospital for Special Care
New Britain, Connecticut, 06053
Hospital for Special Surgery
New York, New York, 10021
Neurological Institute Columbia University Medical Center
New York, New York, 10032
University of California, Irvine
Orange, California, 92868
The Penn Comprehensive Neuroscience Center
Philadelphia, Pennsylvania, 19107
Temple University School of Medicine
Philadelphia, Pennsylvania, 19140
St. Joseph's Hospital & Medical Center - Barrow Neurology Clinics
Phoenix, Arizona, 85013
Providence Brain and Spine Institute ALS Center
Portland, Oregon, 97213
Oregon Health and Science Center
Portland, Oregon, 97239
University of California Davis Medical Center
Sacramento, California, 95817
University of Texas Health Science Center
San Antonio, Texas, 78229
Forbes Norris MDA/ALS Research Center
San Francisco, California, 94115
University of Washington Medical Center
Seattle, Washington, 98195
Saint Louis University
St Louis, Missouri, 63104
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Stanford Hospital and Clinics
Stanford, California, 94305
SUNY Upstate Medical University
Syracuse, New York, 13210
Carol and Frank Morsini Center for Advanced Health Care - University of South Florida
Tampa, Florida, 33612
George Washington University Medical Center
Washington D.C., District of Columbia, 20037
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655
Canada10 sites
University of Calgary
Calgary, Alberta, T3M 1M4
Edmonton Kaye Clinic
Edmonton, Alberta, T6G 1Z1
Stan Cassidy Centre for Rehabilitation
Fredericton, New Brunswick, E3B OC7
QE II Health Sciences Centre, NHI Site
Halifax, Nova Scotia, B3H 1V7
McMaster University Medical Centre
Hamilton, Ontario, L8N 4K1
London Health Sciences Centre
London, Ontario, N6A 5A5
Notre-Dame Hospital/CHUM
Montreal, Quebec, H2L 4M1
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4
CHU de Quebec - Universite Laval Hopital de l'Enfant-Jesus
Québec, G1J 1Z4
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
France7 sites
Hopital R. Salengro, CHRU Lille
Lille, 59037
CHU Dupuytren
Limoges, 87042
Hopital de la Timone
Marseille, 13005
Hopital Gui de Chauliac
Montpellier, 34295
CHU de Nice - Hopital Pasteur 2
Nice, 06001
Hopital de la Salpetriere
Paris, 75651
Bretonneau University Hospital
Tours, 37044
United Kingdom4 sites
Walton Centre for Neurology and Neurosurgery
Liverpool, L9 7LJ
Clinical Research Centre, Royal London Hospital
London, E1 2AT
Kings College Hospital
London, SE59RS
Derriford Hospital
Plymouth, Devon, PL6 8DH
Germany3 sites
Charite Campus Virchow-Klinikum, Neurology Department
Berlin, 13353
Hannover Medical School, Department of Neurology
Hanover, Lower Saxony, 30625
University of Ulm, Department of Neurology
Ulm, Baden-Wurttemberg, 89081
Italy3 sites
IRCCS Istituto Auxologico Italiano - U.O. Neurologia
Milan, 20149
Centro Clinico NEMO - Fondazione Serena Onlus, ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
Dipartimento di Neuroscienze "Rita Levi Moltalcini" A.O.U. Citta della Salute e della Scienza di Torino P.O. "Molinette"
Torino, 10126
Portugal1 site
Hospital Santa Maria-Centro Hospitalar Lisboa Norte
Lisbon, 1649-035
About this study
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)
This study assessed the effect of tirasemtiv versus placebo on respiratory function in patients with ALS.
Read the detailed description
CY 4031 was a multi-national, double-blind, randomized, placebo-controlled, stratified, parallel group study of tirasemtiv in patients with ALS. The study had 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 completed 2 weeks of treatment with open-label tirasemtiv (125 mg twice daily) were randomized 3:2:2:2 to placebo or one of three dose levels of tirasemtiv (250 mg/day, 375 mg/day, or 500 mg/day). Approximately 600 patients were planned to be enrolled into the open-label treatment phase.
Patients taking riluzole at study entry could continue use of riluzole during the study as long as they had been on a stable dose for at least 30 days prior to study screening. In addition, for patients randomized to tirasemtiv, the riluzole dose was reduced to half the approved dose (ie, reduced to 50 mg once daily) because administration of tirasemtiv approximately doubles the exposure to concomitant riluzole. Patients randomized to placebo continued riluzole at 50 mg twice daily. This was accomplished without unmasking the study's blind as follows:
- All patients on riluzole took their morning 50 mg dose of riluzole from their personal riluzole supply.
- The sponsor supplied the evening riluzole dose as double-blind study medication, as follows: (a) for patients randomized to placebo, the double-blind, evening riluzole dose was 50 mg of active riluzole; (b) for patients randomized to tirasemtiv, the double-blind, evening riluzole dose was a matching placebo for riluzole.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Tirasemtiv, Placebo tablets
- Keywords
- fast skeletal troponin activator, tirasemtiv, CK-2017357, double-blind, randomized, placebo-controlled
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirasemtivDrug
Also called CK-2017357
Placebo tabletsDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Placebo | Placebo comparator | Day 1 through Week 48: 2 placebo tablets twice daily Receives: Drug: Placebo tablets |
| Group 2 - 250 mg tirasemtiv | Experimental | Day 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 Receives: Drug: Tirasemtiv; Drug: Placebo tablets |
| Group 3 - 375 mg tirasemtiv | Experimental | Day 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 Receives: Drug: Tirasemtiv; Drug: Placebo tablets |
| Group 4 - 500 mg tirasemtiv | Experimental | Day 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 Receives: Drug: Tirasemtiv; Drug: Placebo tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
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: bulbar functions, fine motor tasks, gross motor tasks, and respiratory function. Respiratory function consists of 3 of the 12 questions, which assess dyspnea, orthopnea, and respiratory insufficiency. Each question is scored from 0 (indicating incapable or dependent) to 4 (normal). The sum of the response to these 3 questions represents the respiratory domain score. The respiratory domain score ranges from 0 to 12, with higher scores reflecting more normal function and lower scores reflecting more impaired function.
Measured: 48 weeks
Slope of Mega-score of Muscle Strength During the 48 Weeks of Double-blind, Placebo-controlled Treatment
A hand-held dynomometer, with a scale of 0 to 300 pounds, was used to measure muscle strength and handgrip strength (bilateral); the muscle groups tested were: elbow flexion (bilateral), wrist extension (bilateral), knee extension (bilateral), and ankle dorsiflexion (bilateral). The muscle strength mega-score was calculated as the average of responses to all tested muscles as well as handgrip strength. The slope of muscle strength mega-score was the change over time (48 weeks) and analyzed using a mixed model that assumed a random slope effect. For this endpoint, negative values indicate a decline in muscle strength over time.
Measured: 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
This endpoint evaluated the time to occurrence of a decline in percent predicted SVC (as measured by spirometry) of ≥ 20 percentage points, or the onset of respiratory insufficiency (defined as tracheostomy or the use of non-invasive ventilation for ≥ 22 hours per day for ≥10 consecutive days), or death, whichever was first, during the 48-week double-blind, placebo-controlled treatment phase.
Note: The median time to a ≥ 20% decline in percent predicted SVC, onset of respiratory insufficiency, or death was 302 days for the placebo group and 359, 334, and 337 days for the 250 mg, 375 mg, and 500 mg tirasemtiv groups, respectively. The data presented for this endpoint are the number and percent of patients who met the endpoint.
Measured: 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
This endpoint evaluated the time to occurrence of a decline in SVC (as measured by spirometry) to ≤ 50% predicted, or the onset of respiratory insufficiency (defined as tracheostomy or the use of non-invasive ventilation for ≥ 22 hours per day for ≥10 consecutive days), or death, whichever was first, during the 48-week double-blind, placebo-controlled treatment phase.
Note: The median time to a decline in SVC to ≤ 50% predicted, onset of respiratory insufficiency, or death was not estimable for the placebo group or the 375 mg tirasemtiv group. The median time was estimated as 363 and 351 days for the 250 mg and 500 mg tirasemtiv groups, respectively. The data presented for this endpoint are the number and percent of patients who met the endpoint.
Measured: 48 weeks
Change From Baseline in the ALSFRS-R Total Score to the End of 48 Weeks of the Double-blind, Placebo-controlled 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.
Measured: 48 weeks
Time to the First Use of Mechanical Ventilatory Assistance or Death During All 48 Weeks of Double-blind, Placebo-controlled Treatment
This endpoint evaluated the time to occurrence of mechanical ventilatory assistance (defined as invasive or non-invasive ventilation for at least 2 hours over a 24-hour period for at least 5 consecutive days) or death, whichever was first, during the 48-week double-blind, placebo-controlled treatment phase.
Note: The median time to first use of mechanical ventilatory assistance or death was not estimable for all but the 375 mg tirasemtiv group (with a value of 367 days). As such the number and percent of patients who met the endpoint (ie, had mechanical ventilatory assistance or died) are presented.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2015 (estimated)
- Study start3 Sep 2015
- Primary completion9 Mar 2017
- Study completion27 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 744 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Cytokinetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02496767
- Sponsor's protocol ID
- CY 4031
- Other IDs
- 2014-005413-23, 2014
- Acronym
- VITALITY-ALS
- Status last verified
- Aug 2020
- First submitted
- 10 Jul 2015
- Last updated
- 9 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 39513379Andrews 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.
PubMed 29402141
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02496767
- Acronym / sponsor ID
- VITALITY-ALS / CY 4031
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- fast skeletal troponin activator, tirasemtiv, CK-2017357, double-blind, randomized, placebo-controlled
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 744 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- 3 Sep 2015 (actual)
- Primary completion
- 9 Mar 2017 (actual)
- Study completion
- 27 Sep 2017 (actual)
- First posted
- 14 Jul 2015 (estimated)
- Results
- Posted 19 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study assessed the effect of tirasemtiv versus placebo on respiratory function in patients with ALS.
Detailed description
CY 4031 was a multi-national, double-blind, randomized, placebo-controlled, stratified, parallel group study of tirasemtiv in patients with ALS. The study had 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 completed 2 weeks of treatment with open-label tirasemtiv (125 mg twice daily) were randomized 3:2:2:2 to placebo or one of three dose levels of tirasemtiv (250 mg/day, 375 mg/day, or 500 mg/day). Approximately 600 patients were planned to be enrolled into the open-label treatment phase.
Patients taking riluzole at study entry could continue use of riluzole during the study as long as they had been on a stable dose for at least 30 days prior to study screening. In addition, for patients randomized to tirasemtiv, the riluzole dose was reduced to half the approved dose (ie, reduced to 50 mg once daily) because administration of tirasemtiv approximately doubles the exposure to concomitant riluzole. Patients randomized to placebo continued riluzole at 50 mg twice daily. This was accomplished without unmasking the study's blind as follows:
- All patients on riluzole took their morning 50 mg dose of riluzole from their personal riluzole supply.
- The sponsor supplied the evening riluzole dose as double-blind study medication, as follows: (a) for patients randomized to placebo, the double-blind, evening riluzole dose was 50 mg of active riluzole; (b) for patients randomized to tirasemtiv, the double-blind, evening riluzole dose was a matching placebo for riluzole.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Placebo | Placebo comparator | Drug: Placebo tabletsDay 1 through Week 48: 2 placebo tablets twice daily |
| Group 2 - 250 mg tirasemtiv | Experimental | Drug: Tirasemtiv, Drug: Placebo tabletsDay 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 | Experimental | Drug: Tirasemtiv, Drug: Placebo tabletsDay 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 | Experimental | Drug: Tirasemtiv, Drug: Placebo tabletsDay 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirasemtivAlso: CK-2017357 | Drug | Group 2 - 250 mg tirasemtiv, Group 3 - 375 mg tirasemtiv, Group 4 - 500 mg tirasemtiv |
| Placebo tablets | Drug | Group 1 - Placebo, Group 2 - 250 mg tirasemtiv, Group 3 - 375 mg tirasemtiv, Group 4 - 500 mg tirasemtiv |
Primary outcome
Change From Baseline to Week 24 of the Double-blind, Placebo-controlled Phase in Percent Predicted Slow Vital Capacity (SVC)
Time frame: 24 weeks
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).
6 secondary outcomes
Change From Baseline in the ALSFRS-R Respiratory Domain Score at the End of 48 Weeks of Double-blind, Placebo-controlled Treatment
Time frame: 48 weeks
Slope of Mega-score of Muscle Strength During the 48 Weeks of Double-blind, Placebo-controlled Treatment
Time frame: 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
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 the 48 Weeks of Double-blind, Placebo-controlled Treatment
Time frame: 48 weeks
Change From Baseline in the ALSFRS-R Total Score to the End of 48 Weeks of the Double-blind, Placebo-controlled Treatment
Time frame: 48 weeks
Time to the First Use of Mechanical Ventilatory Assistance or Death During All 48 Weeks of Double-blind, Placebo-controlled Treatment
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39513379Simkins 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.
- Derived from this study: PubMed 29402141Andrews 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Cytokinetics
81 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tirasemtiv in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 81 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 81 sites in United States, Canada, France, United Kingdom, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 24 of the Double-blind, Placebo-controlled Phase in Percent Predicted Slow Vital Capacity (SVC) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02496767, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.