Primary• To evaluate the effect of CK-3773274 on exercise capacity (VO2) in patients with symptomatic oHCMSecondary• To evaluate the effect of CK-3773274 on patient health status• To evaluate the effect of CK-3773274 on New York Heart Association (…
ID
Source
Brief title
Condition
- Congenital cardiac disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is change in pVO2 by CPET from baseline to
Week 24.
Secondary outcome
• Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score
(KCCQ-CSS) from baseline to Week 12 and Week 24
• Proportion of patients with >=1 class improvement in NYHA Functional Class
from baseline to Week 12 and Week 24
• Change in post-Valsalva LVOT-G from baseline to Week 12 and Week 24
• Proportion of patients with post-Valsalva LVOT-G <30 mmHg at Week 12 and Week
24
• Change in total workload during CPET from baseline to Week 24
Background summary
CK-3773274, a small molecule allosteric inhibitor of cardiac myosin, is being
developed as a chronic oral treatment for patients with HCM. CK-3773274 is
designed to reduce the hypercontractility that underlies the pathophysiology of
HCM in the cardiac sarcomere. The intended pharmacologic effect is reduction in
force produced by the cardiac sarcomere resulting in less LVOT obstruction and
improved diastolic function in patients with oHCM.
CK-3773274 has been studied in a Phase 1 study of healthy adult participants
and a Phase 2 study of patients with oHCM. This Phase 3 trial will assess the
efficacy and safety of CK-3773274 in patients with oHCM.
Study objective
Primary
• To evaluate the effect of CK-3773274 on exercise capacity (VO2) in patients
with symptomatic oHCM
Secondary
• To evaluate the effect of CK-3773274 on patient health status
• To evaluate the effect of CK-3773274 on New York Heart Association (NYHA)
Functional Classification
• To evaluate the effect of CK-3773274 on post-Valsalva left ventricular
outflow tract gradients (LVOT-G)
• To evaluate the effect of CK-3773274 on exercise capacity(total workload)
• To evaluate the effect of CK-3773274 on duration of eligibility for septal
reduction therapy
Safety
• To evaluate the safety and tolerability profile of CK-3773274 in patients
with symptomatic oHCM
For exploratory objectives, please refer to the protocol.
Study design
This is a Phase 3, randomized, placebo-controlled, double-blind, multi-center
trial in patients with symptomatic oHCM. Approximately 270 eligible patients
will be randomized in a 1:1 ratio to receive CK-3773274 or placebo.
IP will be administered orally once daily with or without food. IP doses will
be individually titrated. The primary endpoint of pVO2 will be measured by CPET
at screening and at end of treatment (Week 24). If applicable, patients will
continue taking background HCM medications consistent with regional clinical
practice guidelines during the trial.
Intervention
Subjects will receive CK-3773274 or placebo. CK-3773274 is administered as an
oral 5 mg tablet at doses of 5-20 mg per day.
Study burden and risks
Risks and side effects observed with CK-3773274
CK-3773274 has the potential to reduce heart pumping function too much. This
has been observed in a few study subjects with no other side effect and
improved after the study medicine dose was reduced or discontinued. Since
CK-3773274 is a research medicine, there may be other risks that are unknown.
All medicines have the potential risk of an allergic reaction, which if not
treated promptly, could become life threatening.
Risks from study procedures
Risks and discomforts that subjects may experience from the study procedures
include:
Electrocardiogram (ECG):
Occasionally there may be some minor skin irritation from the adhesive tabs of
the wire electrodes.
Echocardiogram:
The technician will spread gel on the subject*s chest and then press a device
known as a transducer firmly against the skin. The subject may feel some mild
discomfort during the process.
Cardiopulmonary exercise test (CPET):
As during any moderate exercise, the subject will become tired and short of
breath; this is normal. It is likely that the subject*s heart rate and blood
pressure will increase during exercise. In rare instances, abnormal changes may
occur such as fainting, irregular heartbeat and low blood pressure. In very
rare instances heart attack may occur as in any other strenuous activity. Every
effort will be made to minimize any possible risks by constant monitoring of
heart rate, heart rhythm and blood pressure. Trained medical personnel provide
surveillance during testing and may stop the test at any time. Trained medical
personnel and equipment are available to deal with unusual situations, should
they arise.
Oyster Point Boulevard 350
South San Francisco CA 94080
US
Oyster Point Boulevard 350
South San Francisco CA 94080
US
Listed location countries
Age
Inclusion criteria
Males and females between 18 and 85 years of age, inclusive, at screening.
• Body mass index <35 kg/m^2.
• Diagnosed with HCM per the following criteria: * Has LV hypertrophy and
non-dilated LV chamber in the absence of other cardiac disease and
* Has an end-diastolic LV wall thickness as measured by the echocardiography
core laboratory of: • >=15 mm in one or more myocardial segments OR
• >=13 mm in one or more wall segments and a known-disease-causing gene mutation
or positive family history of HCM
• Has resting LVOT-G >=30 mmHg and post-Valsalva LVOT G >=50 mmHg during
screening as determined by the echocardiography core laboratory.
• LVEF >=60% at screening as determined by the echocardiography core laboratory.
• NYHA Functional Class II or III at screening.
• Hemoglobin >=10g/dL at screening.
• Respiratory exchange ratio (RER) >=1.05 and pVO2 <=90% predicted on the
screening CPET per the core laboratory.
• Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have
been on stable doses for >6 weeks prior to randomization and anticipate
remaining on the same medication regimen during the trial. Patients treated
with disopyramide must also be concomitantly treated with a beta blocker and/or
calcium channel blocker
Exclusion criteria
• Known or suspected infiltrative, genetic or storage disorder causing cardiac
hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).
• Significant valvular heart disease (per investigator judgment).
* Moderate-severe valvular aortic stenosis.
* Moderate-severe mitral regurgitation not due to systolic anterior motion of
the mitral valve.
• History of LV systolic dysfunction (LVEF <45%) or stress cardiomyopathy at
any time during their clinical course.
• Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations).
• Has been treated with septal reduction therapy (surgical myectomy or
percutaneous alcohol septal ablation) or has plans for either treatment during
the trial period.
• Documented paroxysmal atrial fibrillation during the screening period.
• Paroxysmal or permanent atrial fibrillation requiring is only excluded IF:
- rhythm restoring treatment (eg, direct-current cardioversion, atrial
fibrillation ablation procedure, or antiarrhythmic therapy) has been required
<=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.)
-rate control and anticoagulation have not been achieved for at least 6 months
prior to screening
• History of syncope or sustained ventricular tachyarrhythmia with exercise
within 6 months prior to screening.
• Has received prior treatment with CK-3773274 or mavacamten.
Exclusion Criteria for CMR sub-study
• Inability to tolerate CMR.
• Has an implantable cardioverter-defibrillator (ICD).
• Has a cardiac pacemaker.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003536-92-NL |
| ClinicalTrials.gov | NCT05186818 |
| CCMO | NL79139.078.22 |