Over 50 clinical trials with a single focus:Improve lives
|GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) – GALACTIC-HF was a Phase 3, double-blind, placebo-controlled, multicenter clinical trial conducted by Amgen in collaboration with Cytokinetics, and one of the largest Phase 3 global cardiovascular outcomes studies in heart failure ever conducted. The trial evaluated the effect of treatment with omecamtiv mecarbil compared with placebo in approximately 8,256 patients with chronic heart failure with reduced ejection fraction (HFrEF) who were at risk of hospitalization and death, despite being well treated on standard of care therapy. After a median duration of follow-up of 21.8 months, the trial demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care (hazard ratio, 0.92; 95% confidence interval, 0.89 to 0.99; p=0.0252). No reduction in the secondary endpoint of time to CV death was observed. Adverse events, including major ischemic cardiac events, were balanced between the treatment arms. These results were published in NEJM, available online here.
A secondary analysis from GALACTIC-HF of ejection fraction as a continuous variable demonstrated a progressively larger treatment effect of omecamtiv mecarbil with decreasing ejection fraction (interaction p = 0.013 by EF quartile). For more information about this trial, click here.
|METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure) – METEORIC-HF is a Phase 3, randomized, placebo-controlled, double-blind, parallel group, multicenter clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) following 20 weeks of treatment. This trial is designed to enroll approximately 270 patients with HFrEF at sites throughout the U.S., Canada and Europe. Patient enrollment was complete in METEORIC-HF in June 2021. For more information about this trial, click here.|
|REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM) – REDWOOD-HCM is a Phase 2, multi-center, randomized, placebo-controlled, double-blind, dose finding clinical trial of aficamten in patients with symptomatic hypertrophic cardiomyopathy (HCM). The primary objective of the trial is to determine the safety and tolerability of aficamten.
Cohorts 1 and 2 enrolled patients with symptomatic obstructive HCM taking background medications exclusive of disopyramide. Results showed that treatment with aficamten for 10 weeks resulted in statistically significant reductions from baseline compared to placebo in the average resting left ventricular outflow tract pressure gradient (LVOT-G) and the average post-Valsalva LVOT-G. A large majority of patients treated with aficamten achieved the target goal of treatment, defined as resting gradient <30 mmHg and post-Valsalva gradient <50 mmHg at Week 10, compared to placebo. Patients treated with aficamten also saw improvements in heart failure symptoms and reductions in NT-proBNP, a biomarker of cardiac wall stress. Treatment with aficamten in REDWOOD-HCM was generally well tolerated and the incidence of adverse events on aficamten was similar to that of placebo. No serious adverse events were attributed to aficamten, and no treatment interruptions occurred on aficamten.
Cohort 3 enrolled patients with symptomatic obstructive HCM taking background medications including disopyramide. Topline results showed that substantial reductions in the average resting LVOT-G and post-Valsalva LVOT-G were achieved, with only modest decreases in average left ventricular ejection fraction (LVEF), and no patients whose LVEF fell below the prespecified safety threshold of 50%. New York Heart Association (NYHA) Functional Class was improved in the majority of patients. Pharmacokinetic data as well as the safety and tolerability of aficamten were consistent with prior experience in REDWOOD-HCM with no treatment interruptions and no serious adverse events attributed to treatment reported by the investigators.
Cohort 4 will enroll, in an open label fashion, 30-40 patients with symptomatic non-obstructive HCM receiving background medical therapy. The primary objective is to determine the safety and tolerability of aficamten in patients with non-obstructive HCM. Other objectives include the effect of aficamten on LVEF, NYHA Functional Class and cardiac biomarkers.
All patients will be eligible to participate in the open label extension study of aficamten, REDWOOD-HCM OLE.
For more information about the trial, click here.
|SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) – SEQUOIA-HCM is a Phase 3 randomized, placebo-controlled, double-blind, multi-center clinical trial designed to evaluate aficamten in patients with symptomatic oHCM on background medical therapy for 24 weeks. The primary objective is to assess the effect of aficamten on change in peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) from baseline to week 24. Secondary objectives include change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score from baseline to week 12 and week 24, the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class from baseline to week 12 and week 24, change in post-Valsalva left ventricular outflow tract gradient (LVOT-G) to week 12 and week 24, the proportion of patients with post-Valsalva LVOT-G <30 mmHg, and change in total workload during CPET to week 24. For more information about the trial, click here.|
|FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints in ALS) – Cytokinetics announced results from FORTITUDE-ALS, a Phase 2, double-blind, randomized, dose-ranging, placebo-controlled, parallel group study of reldesemtiv in patients with ALS at the American Academy of Neurology meeting in May 2019. The trial enrolled 458 patients with ALS in the US, Canada, Europe and Australia. The trial did not achieve statistical significance for its primary endpoint of change from baseline in slow vital capacity (SVC) after 12 weeks of dosing, but all patients on all doses of reldesemtiv declined less than patients on placebo for SVC and ALSFRS-R, with clinically meaningful differences emerging over time.|
|COURAGE-ALS (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS) – COURAGE-ALS is a Phase 3, multi-center, double-blind, randomized, placebo-controlled trial of reldesemtiv expected to enroll approximately 555 patients with ALS. Patients will be randomized 2:1 to receive 300 mg of reldesemtiv or matching placebo dosed orally twice daily for 24 weeks, followed by a 24-week period in which all patients will receive 300 mg of reldesemtiv twice daily. Eligible patients will be within the first two years of their first symptom of muscle weakness, have a vital capacity of ≥65% predicted, and a screening ALS Functional Rating Scale – Revised (ALSFRS-R) ≤44. Patients currently taking stable doses of Radicava® (edaravone) and/or Rilutek® (riluzole) will be permitted and randomization stratified accordingly. The primary efficacy endpoint will be change from baseline to 24 weeks in ALSFRS-R. Secondary endpoints include combined assessment of ALSFRS-R total score, time to onset of respiratory insufficiency and survival time up to week 24 using a joint rank test; change from baseline to 24 weeks for vital capacity; ALSAQ-40; and bilateral handgrip strength. Two unblinded interim analyses by the Data Monitoring Committee are planned. The first interim analysis will assess for futility, 12 weeks after approximately one-third or more of the planned sample size is randomized. A second interim analysis will also assess for futility, and there will be an option for a fixed increase in total enrollment, if necessary, to augment the statistical power of the trial. For more information about the trial, click here.|