Effects of Mavacamten on the Heart in Obstructive Hypertrophic Cardiomyopathy

Who can take part

• The subject has given their written consent to participate in the trial
• Age ≥ 18 years
• Diagnosis of oHCM with unexplained LV hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease and with maximal LV wall thickness ≥15 mm
• Eligible for on-label mavacamten therapy per Swedish prescribing information
• Left ventricular outflow tract (LVOT) ≥ 50 mmHg at rest, during Valsalva or post-exercise
• Left ventricular ejection fraction ≥ 55%
• New York Heart Association (NYHA) class II or III symptoms
• Participants who are capable of becoming pregnant must not be pregnant or lactating and, if sexually active, must use effective birth control methods (see section 7.4) from the Screening visit through 6 months after the last dose of mavacamten

Who cannot take part

• Previous participation in this trial
• Current treatment (within 14 days prior to screening) or planned treatment during the study with: (a) a strong CYP3A4 inhibitor in participants with poor or unknown CYP2C19 metaboliser phenotype; (b) the simultaneous combination of a strong CYP2C19 inhibitor and a strong CYP3A4 inhibitor; (c) strong inducers of both CYP2C19 and CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, St. John's Wort); or (d) omeprazole or esomeprazole
• Presence or planned implantation of electronic cardiac devices such as ICD or pacemaker
• Known or suspected allergies against any product included in the trial
• History of or planned septal reduction therapy (surgical myectomy or percutaneous alcohol ablation) during trial period
• Treatment or disease which, according to the investigator, can affect treatment or trial results
• Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy
• Has documented obstructive coronary artery disease (>70% stenosis in one or more epicardial coronary arteries) or history of myocardial infarction
• Has any 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
• Reduced kidney function with estimated GFR <30 ml/min/1.73m2
• Severe impairment of liver function (Child-Pugh class C) or if there is an alanine aminotransferase or aspartate aminotransferase result, the value must be <3 × the upper limit of the laboratory reference range
• Unable to comply with the study requirements
• Unable to perform CMR exams
• Body mass index ≥ 40kg/m2
• Participation or recent participation in a clinical trial with an investigational medicinal product within 30 days
• Pregnancy (positive p-hCG test at screening), breastfeeding, or planned pregnancy
• Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of participation in the trial
• Has paroxysmal, intermittent atrial fibrillation with atrial fibrillation present per the investigator’s evaluation of the participant’s ECG at the time of Screening
• Has permanent atrial fibrillation
• Has known moderate or severe (as per investigator’s judgment) aortic valve stenosis at Screening