REDWOOD-HCM: Randomized Evaluation of Dosing With CK-3773274 in Obstructive Outflow Disease in HCM (REDWOOD-HCM)
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| ClinicalTrials.gov Identifier: NCT04219826 |
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Recruitment Status :
Recruiting
First Posted : January 7, 2020
Last Update Posted : August 5, 2021
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Sponsor:
Cytokinetics
Information provided by (Responsible Party):
Cytokinetics
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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 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 48 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 and Left Ventricular Outflow Tract Obstruction |
| Actual Study Start Date : | January 10, 2020 |
| Estimated Primary Completion Date : | September 2021 |
| Estimated Study Completion Date : | September 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial hypertrophic cardiomyopathy
MedlinePlus related topics:
Cardiomyopathy
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: CK-3773274 (5 - 15 mg)
CK-3773274 tablets administered orally |
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Placebo Comparator: Placebo - Cohort 1
Subjects will receive placebo for up to 10 weeks
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Drug: Placebo for CK-3773274
Placebo administered orally |
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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
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Drug: CK-3773274 (10 - 30 mg)
CK-3773274 tablets administered orally |
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Placebo Comparator: Placebo - Cohort 2
Subjects will receive placebo for up to 10 weeks
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Drug: Placebo for CK-3773274
Placebo administered orally |
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Experimental: CK-3773274 & disopyramide - Cohort 3
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
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Drug: CK-3773274 (5 - 15 mg)
CK-3773274 tablets administered orally |
Primary Outcome Measures :
- 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 :
- 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%
- 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)
- 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
- 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
- Dose response relationship of CK-3773274 in patients with oHCM at rest [ Time Frame: 10 weeks ]Change from baseline in resting LVOT-G over time as a function of dose
- Dose response relationship of CK-3773274 in patients with oHCM post-Valsalva [ Time Frame: 10 weeks ]Change from baseline in post-Valsalva LVOT-G over time as a function of dose
- 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
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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.
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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.
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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.
- 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.
- For Cohorts 1 and 2: 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).
- 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
Contacts
| Contact: Cytokinetics, MD | 650-624-2929 | medicalaffairs@cytokinetics.com |
Locations
Show 22 study locations
Sponsors and Collaborators
Cytokinetics
Investigators
| Study Director: | Cytokinetics, MD | Cytokinetics |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | August 5, 2021 |
| Last Verified: | August 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Cytokinetics:
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CK-3773274 CK-274 obstructive hypertrophic cardiomyopathy oHCM REDWOOD-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 |