AzTrials
AzTrials

Amyotrophic Lateral SclerosisPhase 2FORTITUDE-ALSNCT03160898

A Study to Evaluate Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS)

A Phase 2 study testing Reldesemtiv in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 64 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study was to assess the effect of CK-2127107 (hereafter referred to as reldesemtiv) versus placebo on respiratory function and other measures of skeletal muscle function in patients with ALS. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Amyotrophic Lateral Sclerosis
What is being tested?
Reldesemtiv
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
458 participants
Where
64 sitesin 6 countries
Study dates
24 Jul 2017to 7 Mar 2019
Phase
Phase 2
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of familial or sporadic ALS ≤ 24 months prior to screening
  • Upright Slow Vital Capacity (SVC) ≥ 60% of predicted for age, height and sex at screening
  • Able to swallow tablets
  • A caregiver (if one is needed)
  • Able to perform reproducible pulmonary function tests
  • Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
Show all 10Show fewer
  • Male patients who have not had a vasectomy and confirmed zero sperm count must agree after receiving the first dose of study drug until 10 weeks after the last dose to either use acceptable methods of contraception or abstain from sex
  • Female patients must be post-menopausal or sterilized or must not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the study and use acceptable methods of contraception or abstain from heterosexual intercourse from Screening until 10 weeks after last dose of study drug
  • Patients must be either on riluzole for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and not planning to start riluzole during the course of the study.
  • Patients on edaravone must have completed at least 2 cycles of dosing with edaravone at the time of screening or have not taken edaravone for at least 30 days prior to screening and not planning to start edaravone during the course of the study.

Who cannot join

  • At the time of screening, any use of non-invasive ventilation (NIV), e.g. continuous positive airway pressure [CPAP], noninvasive bi-level positive airway pressure [NPPV] or noninvasive volume ventilation [NVV] for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
  • Neurological impairment due to a condition other than ALS
  • 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
  • Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
  • Known to have received CK-2127107 or tirasemtiv in any previous clinical trial
  • Has received or is considering receiving during the course of the study any form of stem cell therapy for the treatment of ALS
Show all 10Show fewer
  • Has received or is considering receiving during the course of the study any form of gene therapy for the treatment of ALS
  • Has received or is considering obtaining during the course of the study a diaphragmatic pacing system
  • History of substance abuse within the past 2 years
  • Use of certain medications

Trial locations and contacts

64 sites in 6 countries.

64 sites in 6 countries

United States47 sites

  • Michigan Medicine

    Ann Arbor, Michigan, 48109

  • Emory Clinic

    Atlanta, Georgia, 30322

  • University of Colorado Hospital Anschutz Outpatient Pavilion

    Aurora, Colorado, 80045

  • Johns Hopkins University - Outpatient Center

    Baltimore, Maryland, 21287

  • University of Vermont Medical Center

    Burlington, Vermont, 05405

  • Neurosciences Institute, Neurology - Charlotte

    Charlotte, North Carolina, 28207

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • Duchossois Center for Advanced Medicine

    Chicago, Illinois, 60637

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Texas Neurology

    Dallas, Texas, 75214

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke Neurological Disorders Clinic

    Durham, North Carolina, 27705

  • University of Florida

    Gainesville, Florida, 32610

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • IU Health Neuroscience Center of Excellence

    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

  • Neurology Associates, P.C.

    Lincoln, Nebraska, 68506

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Froedtert Memorial Lutheran Hospital

    Milwaukee, Wisconsin, 53226

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • West Virginia University, Dept. of Neurology

    Morgantown, West Virginia, 26506-9180

  • Vanderbilt University Medical Center - Clinical Research 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

  • Temple University School of Medicine

    Philadelphia, Pennsylvania, 19140

  • St. Joseph's Hospital and Medical Center - Barrow Neurological Clinics

    Phoenix, Arizona, 85013

  • Providence Brain and Spine Institute ALS Center

    Portland, Oregon, 97213

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • VCU Health - Ambulatory Care Center (ACC)

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • UTHSCSA Medical Arts and Research 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, Department of Neurology

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford Hospital and Clinics

    Stanford, California, 94305

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Carol & Frank Morsani Center for Advanced Healthcare - University of South Florida

    Tampa, Florida, 33612

  • George Washington University Medical Faculty Associates

    Washington D.C., District of Columbia, 20037

  • Wake Forest School of Medicine

    Winston-Salem, North Carolina, 27157

  • University of Massachusetts Memorial Medical Center/University of Massachusetts Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

Canada9 sites

  • University of Calgary, Heritage Medical Research Center

    Calgary, Alberta, T2N 4Z6

  • Edmonton Kaye Clinic

    Edmonton, Alberta, T6GT 1Z1

  • McMaster University Medical Centre

    Hamilton, Ontario, L8N 3Z5

  • London Health Sciences Centre University Hospital

    London, Ontario, N6A 5A5

  • Centre de recherche du Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2X 0A9

  • Montreal Neurological Institute and Hospital

    Montreal, Quebec, H3A 2B4

  • CHU de Quebec-Universite Laval, Hopital de l'Enfant Jesus

    Québec, G1J 1Z4

  • Saskatoon City Hospital

    Saskatoon, Saskatchewan, S7H 0G9

  • Sunnybrook Health Science Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Australia5 sites

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Brain and Mind Centre, The University of Sydney

    Camperdown, New South Wales, 2050

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, 4029

  • The Perron Institute for Neurological and Translation Science

    Nedlands, Western Australia, 6009

  • Department of Neurology, Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

Ireland1 site

  • Beaumont Hospital

    Dublin, Dublin 9

Other trials in Ireland

Netherlands1 site

  • University Medical Center Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Spain1 site

  • Hospital San Rafael Servicio de Neurologia

    Madrid, 28016

Other trials in Spain

About this study

Official title: A Phase 2, Multi-Center, Double-Blind, Randomized, Dose-Ranging, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS)

The purpose of this study was to assess the effect of CK-2127107 (hereafter referred to as reldesemtiv) versus placebo on respiratory function and other measures of skeletal muscle function in patients with ALS.

Read the detailed description

This was a double-blind, randomized, placebo-controlled, dose ranging study of reldesemtiv in patients with ALS. Eligible patients were randomized (1:1:1:1) to receive placebo or one of three doses of reldesemtiv (150, 300, or 450 mg twice daily) for 12 weeks. Randomization was stratified by riluzole concomitant use/non-use and edaravone concomitant use/non-use. Concomitant riluzole and edaravone were allowed as long as the riluzole dose had been stable for at least 30 days prior to screening and edaravone had been taken for 2 cycles prior to screening; these drugs could not be initiated during the study.

A total of 7 study visits were planned: screening, Day 1 (first dosing day), Weeks 2, 4, 8, and 12, and follow-up (4 weeks after the last dose of study drug). Study drug (placebo or reldesemtiv) was to be taken twice daily, approximately 12 hours (± 2 hours) apart and within 2 hours following a meal.

Being tested
Reldesemtiv, Placebo
Keywords
Amyotrophic Lateral Sclerosis, ALS, CK-2127107, Reldesemtiv
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.

  • ReldesemtivDrug

    Also called CK-2127107

    Oral tablet

  • PlaceboDrug

    Oral tablet

Study groups in NCT03160898
Study groupRoleWhat they receive
Reldesemtiv 150 mg twice dailyExperimentalPatients in this arm took 1 reldesemtiv 150 mg oral tablet and 2 matching placebo tablets every 12 hours for 12 weeks.
Receives: Drug: Reldesemtiv
Reldesemtiv 300 mg twice dailyExperimentalPatients in this arm took 2 reldesemtiv 150 mg oral tablets and 1 matching placebo tablet every 12 hours for 12 weeks.
Receives: Drug: Reldesemtiv
Reldesemtiv 450 mg twice dailyExperimentalPatients in this arm took 3 reldesemtiv 150 mg oral tablets every 12 hours for 12 weeks.
Receives: Drug: Reldesemtiv
PlaceboPlacebo comparatorPatients in this arm took 3 placebo oral tablets every 12 hours for 12 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC)

    Slow vital capacity was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, 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 percent predicted values using the Global Lung Initiative equation (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics [eg, height, age, sex]).

    Measured: Baseline to Week 12

Secondary outcomes (2)

  1. Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score

    The ALSFRS-R is used to measure the progression and severity of disability in patients with ALS. The ALSFRS-R consists of 12 questions, assessing a patient's capability and independence in functional activities relevant to ALS, categorized in the following 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. Higher scores reflect more normal function and lower scores reflect more impaired function.

    Measured: Baseline to Week 12

  2. Slope of Muscle Strength Mega-score From Baseline to Week 12

    A hand-held dynamometer, 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, wrist extension, first dorsal interosseous, hip flexion, knee extension, and ankle dorsiflexion; all muscle groups were evaluated bilaterally. For each postbaseline assessment of muscle strength, the percent change from baseline was calculated for each muscle group and handgrip strength, using the following equation: ([postbaseline value - baseline value] / baseline value) × 100. The muscle-strength mega-score was calculated as the average of the changes (ie, percent change from baseline) observed for each of the muscle groups as well as handgrip strength. For this endpoint, negative values indicate a decline in muscle strength.

    Measured: Baseline to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2017
  2. Study start24 Jul 2017
  3. Primary completion7 Mar 2019
  4. Study completion7 Mar 2019

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
458 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03160898
Sponsor's protocol ID
CY 5022
Acronym
FORTITUDE-ALS
Status last verified
Aug 2020
First submitted
12 May 2017
Last updated
11 Sep 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Shefner JM, Jacobsen B, Kupfer S, Malik FI, Meng L, Wei J, Wolff AA, Rudnicki SA. Relationship between quantitative strength and functional outcomes in the phase 2 FORTITUDE-ALS trial. Amyotroph Lateral Scler Frontotemporal Degener. 2024 Feb;25(1-2):162-169. doi: 10.1080/21678421.2023.2252468. Epub 2023 Aug 29.

    PubMed 37641579

  • Shefner JM, Al-Chalabi A, Andrews JA, Chio A, De Carvalho M, Cockroft BM, Corcia P, Couratier P, Cudkowicz ME, Genge A, Hardiman O, Heiman-Patterson T, Henderson RD, Ingre C, Jackson CE, Johnston W, Lechtzin N, Ludolph A, Maragakis NJ, Miller TM, Mora Pardina JS, Petri S, Simmons Z, Van Den Berg LH, Zinman L, Kupfer S, Malik FI, Meng L, Simkins TJ, Wei J, Wolff AA, Rudnicki SA. COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success. Amyotroph Lateral Scler Frontotemporal Degener. 2023 Aug;24(5-6):523-534. doi: 10.1080/21678421.2023.2216223. Epub 2023 May 30.

    PubMed 37254449

  • Gebrehiwet P, Meng L, Rudnicki SA, Sarocco P, Wei J, Wolff AA, Chio A, Andrews JA, Genge A, Jackson CE, Lechtzin N, Miller TM, Shefner JM. MiToS and King's staging as clinical outcome measures in ALS: a retrospective analysis of the FORTITUDE-ALS trial. Amyotroph Lateral Scler Frontotemporal Degener. 2023 May;24(3-4):304-310. doi: 10.1080/21678421.2022.2154678. Epub 2022 Dec 12.

    PubMed 36503310

  • Rudnicki SA, Andrews JA, Genge A, Jackson C, Lechtzin N, Miller TM, Cockroft BM, Malik FI, Meng L, Wei J, Wolff AA, Shefner JM; FORTITUDE-ALS STUDY GROUP. Prescription and acceptance of durable medical equipment in FORTITUDE-ALS, a study of reldesemtiv in ALS: post hoc analyses of a randomized, double-blind, placebo-controlled clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2022 May;23(3-4):263-270. doi: 10.1080/21678421.2021.1946083. Epub 2021 Jul 5.

    PubMed 34218726

  • Shefner JM, Andrews JA, Genge A, Jackson C, Lechtzin N, Miller TM, Cockroft BM, Meng L, Wei J, Wolff AA, Malik FI, Bodkin C, Brooks BR, Caress J, Dionne A, Fee D, Goutman SA, Goyal NA, Hardiman O, Hayat G, Heiman-Patterson T, Heitzman D, Henderson RD, Johnston W, Karam C, Kiernan MC, Kolb SJ, Korngut L, Ladha S, Matte G, Mora JS, Needham M, Oskarsson B, Pattee GL, Pioro EP, Pulley M, Quan D, Rezania K, Schellenberg KL, Schultz D, Shoesmith C, Simmons Z, Statland J, Sultan S, Swenson A, Berg LHVD, Vu T, Vucic S, Weiss M, Whyte-Rayson A, Wymer J, Zinman L, Rudnicki SA. A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2021 May;22(3-4):287-299. doi: 10.1080/21678421.2020.1822410. Epub 2020 Sep 24.

    PubMed 32969758

  • Shefner JM, Cudkowicz ME, Hardiman O, Cockcroft BM, Lee JH, Malik FI, Meng L, Rudnicki SA, Wolff AA, Andrews JA; VITALITY-ALS Study Group. A phase III trial of tirasemtiv as a potential treatment for amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2019;0(0):1-11. doi: 10.1080/21678421.2019.1612922.

    PubMed 31081694

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Reldesemtiv in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 64 sites in 6 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 10 inclusion and 10 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 11 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 64 sites in United States, Canada, Australia, Ireland, Netherlands and 1 more country. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 11 Sep 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 12 in the Percent Predicted Slow Vital Capacity (SVC) (time frame: Baseline to Week 12). 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 NCT03160898, which also lists 6 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 11 Sep 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in