Primary: To determine the safety and tolerability of CK3773274 in patients with symptomatic HCMSecondary: Assess long-term effects of CK3773274 on left ventricular outflow tract gradient (LVOT-G) in patients with oHCM
Source
Brief title
Condition
- Congenital cardiac disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence of adverse events observed during dosing of CK-3773274 in patients
with HCM Patient.
Incidence of reported Adverse Events (AEs).
Secondary outcome
1 Incidence of serious adverse events
2. Incidence of left ventricular ejection fraction (LVEF) < 50% observed during
dosing of CK-3773274 in patients with HCM
3. Long-term effects of CK-3773274 on left ventricular outflow tract gradient
(LVOT G) in patients with oHCM
Background summary
Aficamten is a small molecule allosteric inhibitor of cardiac myosin that is
being developed as a chronic, oral treatment for patients with hypertrophic
cardiomyopathy (HCM). Aficamten is designed to reduce the hypercontractility
that underlies the pathophysiology of HCM, which may be caused by genetic
mutations (or presumed genetic mutations) in the cardiac sarcomere. The
intended pharmacologic effect is a reduction in cardiac contractility while
preserving left ventricular ejection fraction (LVEF). This corresponds to a
measurable reduction in left ventricular outflow tract gradient (LVOT-G) at
rest and during provocation in patients with oHCM.
This is an open label study to collect long-term safety and tolerability data,
including assessments of cardiac structure and function, during chronic dosing
with aficamten. A cardiac magnetic resonance (CMR) imaging sub-study will
assess the effects of long-term dosing on cardiac morphology, function and
fibrosis.
Study objective
Primary: To determine the safety and tolerability of CK3773274 in patients
with symptomatic HCM
Secondary: Assess long-term effects of CK3773274 on left ventricular outflow
tract gradient (LVOT-G) in patients with oHCM
Study design
This is an open-label study of aficamten in patients with HCM. The treatment
duration is anticipated to be multiple years.
Approximately 300 patients will be enrolled in this study. After (up to)
56-days of screening, eligible patients will be administered a daily dose of CK
3773274.
Patients who are open label enrolled in CY 6022 will undergo
echocardiographic-guided dose titration approximately every two weeks during
the first 6 weeks. Patients will then be evaluated approximately every 12 weeks
after the Week 12 visit.
To determine an individually optimized dose, each patient will start at the
lowest dose (5 mg) in the pre-specified dose range and undergo
echocardiography-guided dose titration up to a maximum of 20 mg. Up-titrations
may be made no more frequently than every two weeks. The dose range will be
periodically reassessed in the context of ongoing conduct of other studies of
CK-3773274.
Intervention
All patients will receive aficamten. Route of administration is oral.
Dosage level(s) up to 20mg once daily (5, 10, 15 or 20 mg).
Study burden and risks
Aficamten has the potential to reduce the heart pumping function too much. This
has been observed in a few participants with no other side effect and improved
after the study medicine dose was reduced or discontinued.
Risks and discomforts from the study procedures include:
• Blood Draws: Possible side effects of having blood drawn are tenderness,
pain, bruising, bleeding and/or infection where the needle goes into the skin
and blood vein.
• Heart monitoring device: An ambulatory monitoring device called an E-Patch
(about the size of a deck of cards) will be used to monitor the subject*s
heartbeat. The small device attaches to the chest with an adhesive bandage. The
subject may be asked to shave a part of his chest prior to placing the device,
which may cause irritation. In rare instances, the adhesive bandage may cause
skin irritation. Also, wearing the device may be uncomfortable, such as during
sleep.
• 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 your chest and then press a
device known as a transducer firmly against the skin. The subject may feel some
mild discomfort during the process.
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
• Completion of a Cytokinetics study investigating aficamten. If unable to
complete a qualifying
study due to circumstances not related to compliance or safety, the Medical
Monitor may review and determine eligibility.
• LVEF >=55% at the Screening Visit
Exclusion criteria
Exclusion Criteria
• Has participated in another investigational device or drug study or received
an investigational device or drug <1 month (or 5 half-lives for drugs,
whichever is longer) prior to screening. Other investigational procedures while
participating in this study are not permitted.
• Since completion of a previous study of aficamten has:
* Developed new-onset paroxysmal or permanent atrial fibrillation requiring
rhythm restoring treatment (e.g., direct-current cardioversion, ablation
procedure, or antiarrhythmic therapy) <30 days prior to screening. Patient may
re-screen after 30 days if heart rate (HR) <100 bpm and/or rhythm is stable >30
days.
* Undergone septal reduction therapy (surgical myectomy or transcatheter
alcohol ablation).
• Has current obstructive coronary artery disease (>70% stenosis documented in
one or more arteries)
• Has moderate or severe aortic valve stenosis
• Had a confirmed LVEF <40% with an associated dose interruption during
participation in a prior study with aficamten. If data from the participant's
cohort has been unblinded, the patient may be considered for entry.
• History of syncope or sustained ventricular tachyarrhythmia with exercise
within 30 days prior to screening.
• History of appropriate ICD shock within 30 days prior to screening.
• Has received treatment with 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 | EUCTR2020-003571-17-NL |
ClinicalTrials.gov | NCT04848506 |
CCMO | NL81310.078.22 |