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REDWOOD-HCM: Randomized Evaluation of Dosing With CK-3773274 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 7, 2022
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 hypertrophic cardiomyopathy (HCM).

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
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
Actual Study Start Date : January 10, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: CK-3773274 - Cohort 1 (Obstructive HCM)
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 (Obstructive HCM)
Subjects will receive placebo for up to 10 weeks
Drug: Placebo for CK-3773274
Placebo administered orally

Experimental: CK-3773274 - Cohort 2 (Obstructive HCM)
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 (Obstructive HCM)
Subjects will receive placebo for up to 10 weeks
Drug: Placebo for CK-3773274
Placebo administered orally

Experimental: CK-3773274 & disopyramide - Cohort 3 (Obstructive HCM)
Subjects will receive doses 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Drug: CK-3773274 (5 - 15 mg)
CK-3773274 tablets administered orally

Experimental: CK-3773274 - Cohort 4 (non-obstructive HCM)
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




Primary Outcome Measures :
  1. Incidence of adverse events observed during dosing of CK--3773274 in patients with HCM [ 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 CK-3773274 in patients with HCM [ 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 HCM [ 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 in patients with oHCM (Cohorts 1, 2, 3 only) [ 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 in patients with oHCM (Cohorts 1, 2, 3 only) [ 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 on LVOT-G of CK-3773274 in patients with oHCM at rest (Cohorts 1, 2, 3 only) [ Time Frame: 10 weeks ]
    Change from baseline in resting LVOT-G over time as a function of dose

  6. Dose response relationship on LVOT-G of CK-3773274 in patients with oHCM post-Valsalva (Cohorts 1, 2, 3 only) [ Time Frame: 10 weeks ]
    Change from baseline in post-Valsalva LVOT-G over time as a function of dose

  7. Concentration-response relationship of CK-3773274 on left ventricular ejection fraction (LVEF) over 10 weeks of treatment in patients with HCM [ Time Frame: Day 1 to End of Study (EOS) (Week 14) ]
    Change from baseline in the resting LVEF



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

Inclusion Criteria

  • Males and females between 18 and 85 years of age at screening.
  • Body weight is ≥45 kg at screening.
  • Diagnosed with HCM 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.
  • For Cohorts 1, 2 and 3 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
  • For Cohort 4 has resting and post-Valsalva LVOT-G < 30 mmHg at the time of screening
  • For Cohort 4 has elevated NT-proBNP > 300 pg/mL at the time of screening
  • 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.
  • For Cohort 3: Patients must be taking disopyramide. Patients should have been on stable disopyramide doses for >4 weeks prior to screening 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 (Cohorts 1, 2, and 3 only). Patients having undergone septal reduction therapy > 12 months prior to screening who remain symptomatic from nHCM, and who meet all other criteria for inclusion, may be enrolled in Cohort 4.
  • For Cohorts 1, 2 and 4: Has been treated with disopyramide or antiarrhythmic drugs that have negative inotropic activity within 4 weeks prior to screening. (For Cohort 3, use of disopyramide is required).
  • Has any ECG abnormality considered by the investigator to pose a risk to patient safety (eg, second degree atrioventricular block type II).
  • 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 mavacamten.
  • For Cohort 4: has any documented history of LVOT-G ≥ 30 mmHg at rest, with Valsalva, or with exercise (for subjects who have had prior septal reduction therapy, this exclusion criteria only applies to gradients detected following septal reduction therapy).

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
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Sponsors and Collaborators
Cytokinetics
Investigators
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Study Director: Cytokinetics, MD Cytokinetics
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT04219826    
Other Study ID Numbers: CY 6021
2019-002785-12 ( EudraCT Number )
First Posted: January 7, 2020    Key Record Dates
Last Update Posted: November 7, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
non-obstructive hypertrophic cardiomyopathy
nHCM
hypertrophic cardiomyopathy
HCM
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Aortic Valve Disease
Heart Valve Diseases