Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

REDWOOD-HCM: Randomized Evaluation of Dosing With CK-3773274 in Obstructive Outflow Disease in HCM (REDWOOD-HCM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04219826
Recruitment Status : Active, not recruiting
First Posted : January 7, 2020
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Brief Summary:
This study is being performed to understand the effect of different doses of CK-3773274 on patients with obstructive hypertrophic cardiomyopathy (oHCM).

Condition or disease Intervention/treatment Phase
Obstructive Hypertrophic Cardiomyopathy Drug: CK-3773274 (5 - 15 mg) Drug: CK-3773274 (10 - 30 mg) Drug: Placebo for CK-3773274 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
Actual Study Start Date : January 10, 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021


Arm Intervention/treatment
Experimental: CK-3773274 - Cohort 1
Subjects will receive doses of 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks
Drug: CK-3773274 (5 - 15 mg)
CK-3773274 tablets administered orally

Placebo Comparator: Placebo - Cohort 1
Subjects will receive placebo for up to 10 weeks
Drug: Placebo for CK-3773274
Placebo administered orally

Experimental: CK-3773274 - Cohort 2
Subjects will receive doses 10 - 30 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks
Drug: CK-3773274 (10 - 30 mg)
CK-3773274 tablets administered orally

Placebo Comparator: Placebo - Cohort 2
Subjects will receive placebo for up to 10 weeks
Drug: Placebo for CK-3773274
Placebo administered orally




Primary Outcome Measures :
  1. Incidence of adverse events observed during dosing of CK-3773274 in patients with oHCM [ Time Frame: 14 weeks ]
    Patient incidence of reported adverse events (AEs)


Secondary Outcome Measures :
  1. Incidence of left ventricular ejection fraction (LVEF) < 50% observed during dosing of during dosing of CK-3773274 in patients with oHCM [ Time Frame: 14 weeks ]
    Patient incidence of left ventricular ejection fraction (LVEF) < 50%

  2. Incidence of serious adverse events observed during dosing of CK-3773274 in patients with oHCM [ Time Frame: 14 weeks ]
    Patient incidence of reported serious adverse events (SAEs)

  3. Concentration-response relationship of CK-3773274 on the resting left ventricular outflow tract gradient (LVOT-G) on echocardiogram over 10 weeks of treatment [ Time Frame: 10 weeks ]
    Slope of the relationship of the plasma concentration of CK-3773274 to the change from baseline in the resting LVOT-G

  4. Concentration-response relationship of CK-3773274 on the post-Valsalva left ventricular outflow tract gradient (LVOT-G) on echocardiogram over 10 weeks of treatment [ Time Frame: 10 weeks ]
    Slope of the relationship of the plasma concentration of CK-3773274 to the change from baseline in the post-Valsalva LVOT-G

  5. Dose response relationship of CK-3773274 in patients with oHCM at baseline [ Time Frame: 10 weeks ]
    Change from baseline in resting LVOT-G over time as a function of dose

  6. Dose response relationship of CK-3773274 in patients with oHCM post-Valsalva [ Time Frame: 10 weeks ]
    Change from baseline in post-Valsalva LVOT-G to Week 10

  7. Plasma concentrations of CK-3773274 in patients with oHCM [ Time Frame: Day 1 to End of Study (EOS) (Week 14) ]
    Observed maximum plasma concentration (Cmax) and trough plasma concentration (Ctrough) for CK 3773274 during dosing



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria

  • Males and females between 18 and 85 years of age at screening.
  • Body weight is ≥45 kg at screening.
  • Diagnosed with oHCM per the following criteria:

    • Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease.
    • Has minimal wall thickness ≥15 mm (minimal wall thickness ≥13 mm is acceptable with a positive family history of HCM or with a known disease-causing gene mutation).
  • Adequate acoustic windows for echocardiography.
  • Has LVOT-G during screening as follows:

    • Resting gradient ≥50 mmHg OR
    • Resting gradient ≥30 mmHg and <50 mmHg with post-Valsalva LVOT-G ≥50 mmHg
  • LVEF ≥60% at screening.
  • New York Heart Association (NYHA) Class II or III at screening.
  • Patients on beta-blockers, verapamil, diltiazem, or ranolazine should have been on stable doses for >4 weeks prior to randomization and anticipate remaining on the same medication regimen during the study.

Exclusion Criteria

  • Aortic stenosis or fixed subaortic obstruction.
  • Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).
  • History of LV systolic dysfunction (LVEF <45%) at any time during their clinical course.
  • Documented history of current obstructive coronary artery disease (>70% stenosis in one or more epicardial coronary arteries) or documented history of myocardial infarction.
  • Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the study period.
  • Has been treated with disopyramide or antiarrhythmic drugs that have negative inotropic activity within 4 weeks prior to screening.
  • Paroxysmal atrial fibrillation or flutter documented during the screening period.
  • Paroxysmal or permanent atrial fibrillation requiring rhythm restoring treatment (eg, direct-current cardioversion, ablation procedure, or antiarrhythmic therapy) ≤6 months prior to screening. (This exclusion does not apply if atrial fibrillation has been treated with anticoagulation and adequately rate-controlled for >6 months).
  • History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
  • Has received prior treatment with CK-3773274 or is currently receiving mavacamten.

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): NCT04219826


Locations
Show Show 20 study locations
Sponsors and Collaborators
Cytokinetics
Investigators
Layout table for investigator information
Study Director: Study Director, MD Cytokinetics
Layout table for additonal information
Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT04219826    
Other Study ID Numbers: CY 6021
First Posted: January 7, 2020    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cytokinetics:
CK-3773274
CK-274
obstructive hypertrophic cardiomyopathy
oHCM
REDWOOD-HCM
Additional relevant MeSH terms:
Layout table for MeSH terms
Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases