Clinical Trials

Inclusion Criteria:

• Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent according to federal, local, and institutional guidelines prior to initiation of any study-specific procedure.
• At least 18 years old at screening.
• Body weight > 45 kg at screening.
• Adequate acoustic windows to enable accurate TTE (refer to the central echocardiography laboratory’s manual of operations).
• Diagnosed with oHCM (unexplained LV hypertrophy with nondilated ventricular chambers in the absence of other cardiac [e.g., aortic stenosis, hypertension]) or systemic disease. Patient has maximal septal wall thickness ≥ 15 mm or ≥ 13 mm with family history of HCM consistent with current ACCF/AHA 2011 and/or ESC 2014 guidelines (per the country in which the site is located). Patient must meet ACCF/AHA 2011 and/or ESC 2014 guideline recommendations for invasive SRT therapies as follows:
  • Clinical criteria: Despite maximally tolerated drug therapy severe dyspnea or chest pain (NYHA Class III or IV) or for the purposes of the Valor Study, subjects who are NYHA Class II with exertion-induced syncope or near syncope;
  • Hemodynamic criteria: dynamic LVOT gradient at rest or with provocation (i.e., Valsalva or exercise) ≥ 50 mmHg associated with septal hypertrophy (read by the core echocardiography laboratory);
  • Anatomic criteria: targeted anterior septal thickness sufficient to perform the procedure safely and effectively in the judgment of the individual operator.
• Referred or under active consideration within the past 12 months for SRT procedure and willing to have SRT procedure.
• Subjects referred or considered for ASA must have an adequate first septal perforating branch of left anterior descending (LAD) coronary artery, amenable for the interventionalist to perform the procedure.
• Documented oxygen saturation at rest ≥ 90% at screening.
• Documented LVEF ≥ 60% at screening according to core echocardiography laboratory reading.
• Female subjects not pregnant or lactating and, if sexually active, must either practice true abstinence or use 1 of the following highly effective birth control methods from screening through 3 months after the last dose of study drug:
  • Estrogen- and progestogen-containing hormonal contraception associated with inhibition of ovulation or progestogen-only hormonal contraception associated with inhibition of ovulation by oral, implantable, or injectable route of administration;
  • Intrauterine device;
  • Intrauterine hormone-releasing system;
  • Bilateral tubal occlusion;
  • Female surgically sterile or postmenopausal for 1 year. Permanent sterilization includes hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or documented bilateral tubal occlusion. Females are considered postmenopausal if they have had amenorrhea for ≥1 year after cessation of all exogenous hormonal treatments, and follicle stimulating hormone (FSH) levels are in the postmenopausal range.
• Male partners of female subjects must also use a contraceptive (e.g., barrier, condom, or vasectomy) from screening through 4 months after the last dose of study drug.

Exclusion Criteria:

• Previously participated in a clinical study with mavacamten (individuals who failed screening for a prior mavacamten study may participate).
• Hypersensitivity to any of the components of the mavacamten formulation.
• Participated in a clinical trial in which the subject received any investigational drug (or currently using an investigational device) within 30 days prior to screening, or at least 5 times the respective elimination half-life (whichever is longer).
• Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy.
• Planned invasive procedure during the first 32 weeks of the study.
• Papillary muscle or mitral valve in need of repair or any other intracardiac procedure planned (however, if need for mitral valve repair is discovered during SRT procedure, the subject will continue to be followed on study).
• For individuals on beta blockers, calcium channel blockers, or disopyramide, any dose adjustment of these medications < 14 days prior to screening or an anticipated change in regimen during the first 16 weeks of the study.
• Any medical condition that precludes upright exercise stress testing.
• Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at screening per the investigator’s evaluation of the subject’s electrocardiogram (ECG).
• Persistent or permanent atrial fibrillation and subject not on anticoagulation for ≥ 4 weeks prior to screening and/or not adequately rate controlled ≤ 6 months prior to screening.
• Previously treated with invasive septal reduction (surgical myectomy or percutaneous ASA). However, if the participant has a history of a suboptimal or a failed alcohol septal ablation and there is no evidence on site read prescreening echocardiogram of an ASA, the participant may be included after consultation with the MyoKardia or CRO medical monitor.
• Planned ICD placement or pulse generator change during the first 32 weeks of the study.
• ECG abnormality considered by the investigator to pose a risk to participant safety (eg, second degree atrioventricular block type II).
• Acute or serious comorbid condition (eg, major infection or hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that in the judgment of the investigator could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study:
  • Pulmonary disease that limits exercise capacity or systemic arterial oxygen saturation;
  • History of malignant disease within 10 years prior to screening:
    • Subjects who have been successfully treated for nonmetastatic cutaneous squamous cell or basal cell carcinoma or have been adequately treated for cervical carcinoma in situ or breast ductal carcinoma in situ may be included in the study;
    • Subjects with other malignancies who are cancer-free for more than 10 years prior to screening may be included in the study.
• History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to subject safety or interfere with study evaluations, procedures, or completion.
• Safety laboratory parameters (chemistry, hematology, coagulation, and urinalysis) outside normal limits (according to the central laboratory reference range) at screening as assessed by the central laboratory; however, a subject with safety laboratory parameters outside the normal limits may be included if all the following criteria are met:
  • Safety laboratory parameters outside normal limits are considered by the investigator to be clinically not significant;
  • If an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) result, the value must be < 3 × the upper limit of the laboratory reference range;
  • Body size–adjusted estimated glomerular filtration rate is ≥ 30 mL/min/1.73 m^2.
• Has known moderate or severe aortic valve stenosis or moderate to severe aortic stenosis determined at screening (as read by the echocardiography core laboratory).
• Positive serologic test at screening for infection with human immunodeficiency virus (HIV); hepatitis C virus (HCV); or hepatitis B virus (HBV), with the exception of HBV s-antibody positive which is a marker of immunity.
• Known active infection with Covid-19 (PCR+) within 90 days of screening. If subject had a PCR+ test within 6 months of screening, they must have a negative Covid-19 test at screening.
• Prior treatment with cardiotoxic agents, such as doxorubicin or similar.
• Unable to comply with the study requirements, including the number of required visits to the study site.
• First-degree relative of personnel directly affiliated with the study at the study site, any study vendor, or the study sponsor.

Eligibility last updated 10/14/21. Questions regarding updates should be directed to the study team contact.