CTRI/2025/07/091820已完成4 期
A Phase 4, Single-Arm, Open-Label Study to Evaluate Safety, Tolerability, and Efficacy of Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy in India (ROVER)
BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED25 个研究点 分布在 1 个国家目标入组 50 人开始时间: 2025年8月18日最近更新:
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 25
- 主要终点
- Incidence of serious Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This Phase 4, single-arm open-label study is designed to evaluate the safety, tolerability, and efficacy of mavacamten in participants with symptomatic obstructive HCM in India. Mavacamten is a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin adenosine triphosphatase (ATPase) specifically developed to target the underlying pathophysiology of hypertrophic cardiomyopathy (HCM) by reducing actin–myosin cross-bridge formation, thereby reducing contractility and improving myocardial energetics.
In the EXPLORER-HCM (MYK-461-005) Phase 3 study, mavacamten treatment was also effective in reducing left ventricular outflow tract (LVOT) peak gradients and improving symptoms, exercise performance, and health status, as shown by significant improvement in all secondary endpoints.
Main estimand for the primary objective:
Treatment: Mavacamten, Population: Adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in India, Variable: Incidence of serious TEAE, Population-level summary: Percentage of participants with any serious TEAEs, Intercurrent event (strategy): study intervention discontinuation (all serious TEAEs that occur after last dose of study intervention +8 weeks for non-poor metabolizers (Non-PMs) or +18 weeks for poor metabolizers [PMs] will be included in the analysis)
Approximately 50 participants will be treated with mavacamten. It is estimated that approximately 100 screened participants will be required to achieve the 50 treated participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Signed Written Informed Consent a.
- •Participants must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines.
- •This ICF must be obtained before performing any protocol related procedures that are not part of normal patient care.
- •Type of Participant and Target Disease Characteristics -a.
- •Is able to understand and comply with the study procedures, understand the risks involved in the study, and provide informed consent according to federal, local, and institutional guidelines before the first study-specific procedure.
- •Diagnosed with obstructive HCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines, ie, satisfy all criteria below.i) Has unexplained LV hypertrophy with nondilated ventricular chambers in the absence of other cardiac
- •Diagnosed with obstructive HCM consistent with current American College of Cardiology Foundation or American Heart Association and European Society of Cardiology guidelines, ie, satisfy all criteria below.
- •i) Has unexplained LV hypertrophy with nondilated ventricular chambers in the absence of other cardiac (ie, hypertension, aortic stenosis) or systemic disease and with maximal LV wall thickness greater than or equal to 15 mm or greater than or equal to 13 mm with positive family history of hypertrophic cardiomyopathy.
- •Has LVOT peak gradient greater than or equal to 50 mmHg during screening as assessed by TTE at rest Valsalva maneuver, or post exercise LVOT peak gradient.
- •d Has LVOT peak gradient with Valsalva at screening TTE of greater than or equal to 30 mmHg. e Has adequate acoustic windows to enable accurate TTEs. f Has NYHA Class II or III symptoms at screening.
- •g Body weight is greater than 45 kg at screening.
- •h Documentation of LVEF greater than or equal to 55 percent at rest of screening TTE.
- •Age of Participant a.
- •Participants must be at least 18 years of age at the time of signing the ICF.
- •Reproductive Status • The investigator shall counsel individuals of childbearing potential (IOCBP) participants (as defined in Appendix 4) on the importance of pregnancy prevention and the implications of an unexpected pregnancy.
- •• The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
- •• Local laws and regulations may require the use of alternative and/or additional contraceptive methods.
- •Female (as assigned at birth) participants: i.
- •Female (as assigned at birth) participants, who are not of childbearing potential, must have documented proof.
- •Note: Documentation can be obtained from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview.
- •o Individuals who are not of childbearing potential (as defined in Appendix 4) are exempt from contraceptive requirements.
- •IOCBP must have a negative highly sensitive urine and serum (at screening) pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention.
- •In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- •• Additional requirements for pregnancy testing during and after study intervention are in Section 2: Schedule of Activities.
- •• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of a individual with an undetected pregnancy.
- •IOCBP must agree to follow instructions for method(s) of contraception as described below and included in the ICF.
- •A female (as assigned at birth) is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies: • Is not an IOCBP OR • Is an IOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 percent per year), as described in Appendix 4, during the intervention period and for at least 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period.
排除标准
- •Medical Conditions a.
- •Known infiltrative or storage disorder causing cardiac hypertrophy that mimics obstructive hypertrophic cardiomyopathy, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy.
- •Septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA]) within 6 months prior to screening or plans to have either of these treatments during the study (note: individuals with an unsuccessful myectomy or percutaneous ASA procedure performed greater than 6 months prior to screening may be enrolled if study eligibility criteria for LVOT peak gradient criteria are met).
- •Has paroxysmal atrial fibrillation present per the investigator’s evaluation of the participant’s ECG at the time of screening.
- •Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to screening and/or not adequately rate controlled within 6 months prior to screening.
- •(Note: Participants with persistent or permanent atrial fibrillation who are anticoagulated and adequately rate-controlled are allowed).
- •Has a history of syncope with exercise within 6 months prior to screening.
- •History of sustained ventricular tachyarrhythmia (greater than 30 seconds) within 6 months prior to screening.
- •g Implantable cardioverter-defibrillator (ICD) placement within 2 months prior to screening or planned ICD placement during the study.
- •h Has documented obstructive coronary artery disease (greater than 70 percent stenosis in one or more epicardial coronary arteries) or history of myocardial infarction.
- •i Has known moderate or severe (as per Investigator’s judgment) aortic valve stenosis at screening visit.
- •j Has participated in a clinical trial in which the participant received any investigational drug (or is currently using an investigational device) within 30 days prior to screening or at least 5 times the respective elimination half-life (whichever is longer).
- •(Prior participation in a non-interventional observational study is allowed.) k Has a history of resuscitated sudden cardiac arrest or known history of appropriate implantable cardioverter-defibrillator (ICD) discharge for life-threatening ventricular arrhythmia.
- •(Note: history of anti-tachycardia pacing is allowed.) l 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.
- •m History of clinically significant malignant disease: participants 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 can be included in the study.
- •n Is unable to comply with the study requirements, including the number of required visits to the clinical site.
- •o Is employed by or is a relative of someone employed by the Sponsor, the Investigator, or his/her staff or family.
- •Reproductive Status a.
- •Individuals who are breastfeeding b.
- •Individuals who are of childbearing potential 3) Prior/Concomitant Therapy a.
- •Is currently taking, or has taken within 14 days of screening, a prohibited medication such as a CYP2C19 inhibitor (eg, omeprazole).
- •Previous or current use of cardiac myosin inhibitor.
- •Physical and Laboratory Test Findings a.
- •Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population.
- •Has any ECG abnormality considered by the Investigator to pose a risk to participant safety (eg, second-degree atrioventricular block type II).
- •Positive urine/serum screen for drugs of abuse.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of the laboratory reference range or total bilirubin greater than or equal to 2 times the upper limit of the laboratory reference range.
- •Renal function less than 30% of normal for age, gender, and height as determined by the Schwartz formula: (glomerular filtration rate GFR [mL/min/1.73m2] = [0.413 times the height (cm)] / serum creatinine mg/dL).
- •Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus (HIV)-1 and HIV-2 antibody if deemed to be clinically significant per the determination of the Principal Investigator in conjunction with the Sponsor Medical Monitor.
- •Allergies and Adverse Drug Reactions a.
- •Other Exclusion Criteria a.
- •Prisoners or participants who are involuntarily incarcerated.
- •Participation in another clinical trial concurrent with this study.
- •Any significant acute or chronic medical illness that in the opinion of the investigator could prevent participation in the study and follow-up.
- •Inability to tolerate oral medication.
- •Inability to be venipunctured and/or tolerate venous access.
结局指标
主要结局
Incidence of serious Treatment Emergent Adverse Events (TEAEs)
时间窗: Baseline (Day 1) to EOS (follow up week 8 or 18 as per protocol)
(Number and percentage /descriptive statistics)
时间窗: Baseline (Day 1) to EOS (follow up week 8 or 18 as per protocol)
次要结局
- Incidence of major adverse cardiac events (CV death, non-fatal stroke, non-fatal myocardial infarction, hospitalization for heart failure.(Incidence of CV hospitalizations)
研究者
研究点 (25)
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