Dose-finding Study to Evaluate the Safety, Tolerability,... | NCT04219826 | Trialant
NCT04219826
Sponsor
Cytokinetics
Status
Completed
Last Update Posted
Feb 24, 2026Actual
Enrollment
96Actual
Phase
Phase 2
Conditions
Hypertrophic Cardiomyopathy (HCM)
Interventions
CK-3773274 (5 - 15 mg)
CK-3773274 (10 - 30 mg)
Placebo for CK-3773274
Countries
United States
Italy
Netherlands
Spain
Protocol Section
Identification Module
NCT ID
NCT04219826
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CY 6021
Secondary IDs
ID
Type
Description
Link
2019-002785-12
EudraCT Number
Brief Title
Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy
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
Acronym
REDWOOD-HCM
Organization
CytokineticsINDUSTRY
Status Module
Record Verification Date
Dec 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 10, 2020Actual
Primary Completion Date
Feb 28, 2023Actual
Completion Date
Feb 28, 2023Actual
First Submitted Date
Jan 3, 2020
First Submission Date that Met QC Criteria
Jan 3, 2020
First Posted Date
Jan 7, 2020Actual
Results Waived
Not provided
Results First Submitted Date
Nov 26, 2025
Results First Submitted that Met QC Criteria
Feb 5, 2026
Results First Posted Date
Feb 24, 2026Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Nov 30, 2023
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Feb 24, 2026Actual
Last Update Submitted Date
Feb 5, 2026
Last Update Posted Date
Feb 24, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
CytokineticsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study is being performed to understand the effect of different doses of CK-3773274 on patients with hypertrophic cardiomyopathy (HCM).
Detailed Description
This was a Phase 2, multi-center, randomized, placebo-controlled, double-blind, dose-finding study in participants with symptomatic HCM. The study consisted of 4 cohorts. For Cohorts 1 and 2, participants with obstructive HCM (oHCM) and not receiving disopyramide were randomized 2:1 to active or placebo treatment and received up to 3 escalating doses of aficamten (5, 10, and 15 mg once daily in Cohort 1 and 10, 20, and 30 mg once daily in Cohort 2) or placebo based on site-read echocardiographic guidance. Cohort 3 consisted of participants with oHCM whose background HCM therapy included disopyramide. All participants in Cohort 3 received up to 3 escalating doses of aficamten (5, 10, and 15 mg once daily) based on echocardiographic guidance. Cohort 4 consisted of participants with non-obstructive HCM (nHCM) on standard of care background therapy. Cohort 4 participants received up to 3 doses of aficamten (5, 10, and 15 mg once daily), titrated based on site-read echocardiographic guidance.
In all 4 cohorts, treatment duration was 10 weeks with a 4-week follow-up period after the last dose.
Conditions Module
Conditions
Hypertrophic Cardiomyopathy (HCM)
Keywords
CK-3773274
CK-274
obstructive hypertrophic cardiomyopathy
oHCM
REDWOOD-HCM
non-obstructive hypertrophic cardiomyopathy
nHCM
hypertrophic cardiomyopathy
HCM
aficamten
CY 6021
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
96Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1 (oHCM) - Aficamten
Experimental
Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Drug: CK-3773274 (5 - 15 mg)
Cohort 1 (oHCM) - Placebo
Placebo Comparator
Participants received placebo once daily for up to 10 weeks
Drug: Placebo for CK-3773274
Cohort 2 (oHCM) - Aficamten
Experimental
Participants received CK-3773274 doses 10 - 30 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Drug: CK-3773274 (10 - 30 mg)
Cohort 2 (oHCM) - Placebo
Placebo Comparator
Participants received placebo once daily for up to 10 weeks
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participant incidence of reported AEs to determine the safety and tolerability of aficamten in participants with HCM.
14 weeks
Incidence of Left Ventricular Ejection Fraction (LVEF) < 50%
Participant incidence of LVEF < 50% as assessed by the core laboratory assessment.
14 weeks
Incidence of Serious Adverse Events (SAEs)
Participant incidence of reported SAEs to determine the safety and tolerability of aficamten in participants with symptomatic HCM.
14 weeks
Secondary Outcomes
Measure
Description
Time Frame
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting Left Ventricular Outflow Track Gradient (LVOT-G)
Concentration-response relationship of CK-3773274 on the resting LVOT-G on echocardiogram over 10 weeks of treatment in participants with (oHCM) obstructive hypertrophic cardiomyopathy (oHCM) (Cohorts 1, 2, 3 only)
Baseline and 10 weeks
Other Outcomes
Not provided
Eligibility Module
Eligibility 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).
Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Drug: CK-3773274 (5 - 15 mg)
Cohort 4 (nHCM) - Aficamten
CK-3773274 (10 - 30 mg)
Drug
CK-3773274 tablets administered orally once daily
Cohort 2 (oHCM) - Aficamten
Placebo for CK-3773274
Drug
Placebo administered orally once daily
Cohort 1 (oHCM) - Placebo
Cohort 2 (oHCM) - Placebo
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Post-Valsalva LVOT-G
Concentration-response relationship of CK-3773274 on the post-Valsalva LVOT-G on echocardiogram over 10 weeks of treatment in participants with oHCM (Cohorts 1, 2, 3 only)
Baseline and 10 Weeks
Change From Baseline in Resting LVOT-G Over Time as a Function of Dose.
Dose response relationship on resting LVOT-G of CK-3773274 in participants with oHCM (Cohorts 1, 2, 3 only)
Baseline and 10 Weeks
Change From Baseline in Post-Valsalva LVOT-G Over Time as a Function of Dose.
Dose response relationship of CK-3773274 on post-Valsalva LVOT-G in participants with symptomatic oHCM (Cohorts 1, 2, 3 only)
10 weeks
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting LVEF
Concentration-response relationship of CK-3773274 on LVEF over 10 weeks of treatment in participants with HCM
Day 1 to End of Study (EOS) (Week 14)
San Francisco
California
94143
United States
Northwestern University
Evanston
Illinois
60208
United States
Tufts Medical Center
Boston
Massachusetts
02111
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Brigham and Women's Hospital
Boston
Massachusetts
02115
United States
Michigan Medicine - University of Michigan
Ann Arbor
Michigan
48109
United States
Washington University School of Medicine
St Louis
Missouri
63110
United States
New York University Langone Health Medical Center
New York
New York
10016
United States
Carolinas Medical Center
Charlotte
North Carolina
28203
United States
Duke Cardiology at Southpoint
Durham
North Carolina
27713
United States
Oregon Health and Science University
Portland
Oregon
97239
United States
Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)
Philadelphia
Pennsylvania
19104
United States
UMPC Heart and Vascular Institute
Pittsburgh
Pennsylvania
15213
United States
UT Southwestern Medical Center
Dallas
Texas
75390
United States
Houston Methodist Hospital
Houston
Texas
77030
United States
Intermountain Medical Center
Murray
Utah
84107
United States
University of Virginia Health System
Charlottesville
Virginia
22903
United States
Azienda Ospedaliero Universitaria Careggi
Florence
Italy
Erasmus University Medical Center (Erasmus MC)
Rotterdam
Netherlands
Complejo Hospitalario Universitario A Coruña
A Coruña
15003
Spain
Hospital Universitario Puerta de Hierro de Majadahonda
Madrid
Spain
Derived
Zampieri M, Argiro A, Marchi A, Berteotti M, Targetti M, Fornaro A, Tomberli A, Stefano P, Marchionni N, Olivotto I. Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy. Curr Cardiol Rep. 2021 Jun 3;23(7):79. doi: 10.1007/s11886-021-01508-0.
Participants received placebo once daily for up to 10 weeks
Placebo for CK-3773274: Placebo administered orally once daily
FG002
Cohort 2 (oHCM) - Aficamten
Participants received CK-3773274 doses 10 - 30 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting Left Ventricular Outflow Track Gradient (LVOT-G)
Concentration-response relationship of CK-3773274 on the resting LVOT-G on echocardiogram over 10 weeks of treatment in participants with (oHCM) obstructive hypertrophic cardiomyopathy (oHCM) (Cohorts 1, 2, 3 only)
The Pharmacodynamics Analysis Set (PDS) included all participants who received at least 1 dose of IP and had a baseline and at least 1 post-baseline core laboratory echocardiography assessment including non-missing LVEF measurements and non-missing LVOT-G at rest.
Posted
Least Squares Mean
90% Confidence Interval
mmHg per ng/ML
Baseline and 10 weeks
ID
Title
Description
OG000
Cohort 1 (oHCM) - Aficamten
Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Post-Valsalva LVOT-G
Concentration-response relationship of CK-3773274 on the post-Valsalva LVOT-G on echocardiogram over 10 weeks of treatment in participants with oHCM (Cohorts 1, 2, 3 only)
The Pharmacodynamics Analysis Set (PDS) included all participants who received at least 1 dose of IP and had a baseline and at least 1 post-baseline core laboratory echocardiography assessment including non-missing LVEF measurements and non-missing LVOT-G at rest.
Posted
Least Squares Mean
90% Confidence Interval
mmHg per ng/ML
Baseline and 10 Weeks
ID
Title
Description
OG000
Cohort 1 (oHCM) - Aficamten
Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Change From Baseline in Resting LVOT-G Over Time as a Function of Dose.
Dose response relationship on resting LVOT-G of CK-3773274 in participants with oHCM (Cohorts 1, 2, 3 only)
The Pharmacodynamics Analysis Set (PDS) included all participants who received at least 1 dose of IP and had a baseline and at least 1 post-baseline core laboratory echocardiography assessment including non-missing LVEF measurements and non-missing LVOT-G at rest.
Posted
Mean
Standard Deviation
mmHg
Baseline and 10 Weeks
ID
Title
Description
OG000
Cohort 1 (oHCM) - Aficamten
Participants received CK-3773274 doses of 5 - 15 mg once daily (QD) with dose levels guided by echocardiography assessments for up to 10 weeks
Change From Baseline in Post-Valsalva LVOT-G Over Time as a Function of Dose.
Dose response relationship of CK-3773274 on post-Valsalva LVOT-G in participants with symptomatic oHCM (Cohorts 1, 2, 3 only)
The Pharmacodynamics Analysis Set (PDS) included all participants who received at least 1 dose of IP and had a baseline and at least 1 post-baseline core laboratory echocardiography assessment including non-missing LVEF measurements and non-missing LVOT-G at rest.
Posted
Mean
Standard Deviation
mmHg
10 weeks
ID
Title
Description
OG000
Cohort 1 (oHCM) - Aficamten
Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting LVEF
Concentration-response relationship of CK-3773274 on LVEF over 10 weeks of treatment in participants with HCM
The Pharmacodynamics Analysis Set (PDS) included all participants who received at least 1 dose of IP and had a baseline and at least 1 post-baseline core laboratory echocardiography assessment including non-missing LVEF measurements and non-missing LVOT-G at rest.
Posted
Least Squares Mean
90% Confidence Interval
percentage per ng/ML
Day 1 to End of Study (EOS) (Week 14)
ID
Title
Description
OG000
Cohort 1 (oHCM) - Aficamten
Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participants received CK-377327 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0000 affected14 at risk
EG0010 affected7 at risk
EG0021 affected14 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Cytokinetics agreement with investigators vary; constant is Cytokinetics' right to review communications regarding trial results prior to public release. Cytokinetics does not prohibit investigators from publishing, but single-center publications must be postponed until after release of the first multi-center publication for the trial. Investigators may not disclose previously undisclosed confidential information other than study data and results from their site.
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
This statistical analysis is reporting the least squares mean difference of the aficamten group vs. placebo in change from baseline in resting LVOT-G for Cohort 1
Superiority
OG002
OG003
LS Mean Difference
-24.7
Standard Error of the Mean
7.0
2-Sided
90
-36.5
-12.8
This statistical analysis is reporting the least squares mean difference of the aficamten group vs. placebo in change from baseline in resting LVOT-G for Cohort 2
Superiority
OG003
Cohort 2 (oHCM) - Placebo
Participants received placebo once daily for up to 10 weeks
Placebo for CK-3773274: Placebo administered orally once daily
Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
This statistical analysis is reporting the least squares mean difference of the aficamten group vs. placebo in change from baseline in post-Valsalva LVOT-G for Cohort 1
Superiority
OG002
OG003
LS Mean Difference
-45.8
Standard Error of the Mean
9.2
2-Sided
90
-61.3
-30.3
This statistical analysis is reporting the least squares mean difference of the aficamten group vs. placebo in change from baseline in post-Valsalva LVOT-G for Cohort 2
Superiority
OG003
Cohort 4 (nHCM) - Aficamten
Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks