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Registrational Study With Omecamtiv Mecarbil (AMG 423) to Treat Chronic Heart Failure With Reduced Ejection Fraction (GALACTIC-HF)

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ClinicalTrials.gov Identifier: NCT02929329
Recruitment Status : Completed
First Posted : October 11, 2016
Results First Posted : July 20, 2021
Last Update Posted : November 5, 2021
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Brief Summary:
The purpose of this study is to determine if treatment with omecamtiv mecarbil when added to standard of care is well tolerated and superior to placebo in reducing the risk of cardiovascular death or heart failure events in adults with chronic heart failure with reduced ejection fraction (HFrEF).

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Omecamtiv Mecarbil Drug: Placebo Drug: Standard of Care Phase 3

Detailed Description:
This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8256 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Omecamtiv Mecarbil on Mortality and Morbidity in Subjects With Chronic Heart Failure With Reduced Ejection Fraction (GALACTIC-HF)
Actual Study Start Date : January 6, 2017
Actual Primary Completion Date : September 14, 2020
Actual Study Completion Date : September 14, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Omecamtiv Mecarbil
Participants received oral omecamtiv mecarbil (OM) twice daily in addition to standard heart failure therapy. The starting dose of OM was 25 mg; At week 4, participants with week 2 OM predose plasma concentrations < 200 ng/mL had their dose increased to 50 mg BID; participants with week 2 predose plasma concentrations ≥ 200 and < 300 ng/mL had their dose increased to 37.5 mg BID and participants with week 2 predose plasma concentrations ≥ 300 ng/mL and < 1000 ng/mL maintained a 25 mg BID dosing regimen.
Drug: Omecamtiv Mecarbil
Omecamtiv mecarbil tablets for oral administration
Other Name: AMG 423

Drug: Standard of Care
Participants were required to be optimally managed with standard of care therapies for chronic HF (eg, beta blockers, renin angiotensin aldosterone system inhibitors), consistent with regional clinical practice guidelines, unless contraindicated.

Placebo Comparator: Placebo
Participants received matching placebo tablets twice a day in addition to standard heart failure therapy.
Drug: Placebo
Matching placebo tablets

Drug: Standard of Care
Participants were required to be optimally managed with standard of care therapies for chronic HF (eg, beta blockers, renin angiotensin aldosterone system inhibitors), consistent with regional clinical practice guidelines, unless contraindicated.




Primary Outcome Measures :
  1. Time to Cardiovascular Death or First Heart Failure Event [ Time Frame: From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months. ]

    The primary outcome was a composite of a heart-failure (HF) event or cardiovascular (CV) death, whichever occurred first, in a time-to-event analysis.

    A heart-failure event was defined as an urgent clinic visit, emergency department visit, or hospitalization for subjectively and objectively worsening heart failure leading to treatment intensification beyond a change in oral diuretic therapy.

    All deaths and HF events were adjudicated by an independent external clinical events committee (CEC) at the Duke Clinical Research Institute, using standardized definitions based on the recent American College of Cardiology/American Heart Association (ACC/AHA) standards for endpoint definitions in cardiovascular clinical trials.

    Time to cardiovascular death or first HF event was analyzed using Kaplan-Meier (KM) methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.



Secondary Outcome Measures :
  1. Time to Cardiovascular Death [ Time Frame: From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months. ]

    Cardiovascular death includes acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, death due to cardiovascular (CV) procedures, death due to CV hemorrhage, and death due to other CV causes.

    All deaths were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials.

    Time to cardiovascular death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.


  2. Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at Week 24 [ Time Frame: Baseline and Week 24 ]

    The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire with a 2-week recall period that includes 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy (the patient's understanding of how to manage their heart failure). The symptom frequency and symptom burden domains are merged into a total symptom score. Scores are represented on a 0-to-100-point scale, where lower scores represent more frequent and severe symptoms and scores of 100 indicate no symptoms.

    The change from baseline in KCCQ TSS was analyzed separately for each randomization setting (inpatient and outpatient).

    Least squares means are from the mixed model which includes baseline total symptom score value, region, baseline eGFR, scheduled visit, treatment group and interaction of treatment with scheduled visit as covariates.


  3. Time to First Heart Failure Hospitalization [ Time Frame: From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months. ]

    A HF hospitalization is defined as an event that met all of the following criteria:

    1. The participant was admitted to the hospital with a primary diagnosis of HF;
    2. The length of stay in the hospital extended for at least 24 hours;
    3. The participant exhibited documented new or worsening symptoms due to HF on presentation;
    4. The participant had objective evidence of new or worsening HF;
    5. The participant received initiation or intensification of treatment specifically for HF, including an intravenous diuretic or vasoactive agent, mechanical or surgical intervention, or mechanical fluid removal.

    Events were adjudicated by an independent external CEC at the Duke Clinical Research Institute using standardized definitions based on the ACC/AHA standards for endpoint definitions in CV clinical trials.

    Time to first HF hospitalization was analyzed using KM methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event is reported.


  4. Time to All-cause Death [ Time Frame: From randomization up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months. ]

    All events were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials.

    Time to all-cause death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with an event are reported. Events that occurred up to the earliest of last confirmed survival status date or analysis cut-off date (07 August 2020) are included.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Subject has provided informed consent
  • Male or female, ≥ 18 to ≤ 85 years
  • History of chronic heart failure (HF), defined as requiring treatment for HF for a minimum of 30 days before randomization
  • Left ventricle ejection fraction (LVEF) ≤ 35%, per subjects most recent medical record, within 12 months prior to screening.
  • New York Heart Association (NYHA) class II to IV at most recent screening assessment.
  • Managed with HF standard of care (SoC) therapies consistent with regional clinical practice guidelines according to investigator judgment of subject's clinical status
  • Current hospitalization with primary reason of HF OR one of the following events within 1 year of screening: hospitalization with primary reason of HF; urgent visit to emergency department (ED) with primary reason of HF.
  • Elevated B-type natriuretic peptide (BNP) or n-terminal-prohormone brain natriuretic peptide (NT-proBNP)

Other Inclusion Criteria May apply

Key Exclusion Criteria:

  • Currently receiving treatment in another investigational device or drug study, or < 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
  • Malignancy within 5 years prior to randomization with the following exceptions: localized basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, stage 1 prostate carcinoma, breast ductal carcinoma in situ.
  • Subject has known sensitivity to any of the products or components to be administered during testing

Other Exclusion Criteria May apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02929329


Locations
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Sponsors and Collaborators
Cytokinetics
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Cytokinetics:
Study Protocol  [PDF] November 13, 2018
Statistical Analysis Plan  [PDF] June 16, 2020

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT02929329    
Other Study ID Numbers: 20110203
2016-002299-28 ( EudraCT Number )
First Posted: October 11, 2016    Key Record Dates
Results First Posted: July 20, 2021
Last Update Posted: November 5, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: https://www.amgen.com/datasharing
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases