2024-511377-30-00招募中3 期
A Phase 2/3 Multicenter, Randomized, Double-blind, Placebo-controlled and Open-label Extension Trial to Evaluate the Efficacy and Safety of Aficamten in a Pediatric Population with Symptomatic Obstructive Hypertrophic Cardiomyopathy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- P1: Change in Valsalva LVOT-G while maintaining LVEF ≥ 55% from baseline to Week 12
研究概览
简要总结
P1: To assess the effect of aficamten compared with placebo on change from baseline in Valsalva LVOT-G
P2: To determine the safety of aficamten in pediatric participants with symptomatic oHCM
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Period Two – Open-Label Extension
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •P1: Males and females between 12 and < 18 years of age at screening and at Day
- •P1: Body weight ≥ 45 kg for the initial cohort and then body weight ≥ 35 kg after at least 10 participants in the initial cohort have undergone dose titration up to Week 4 without observed events of LVEF < 50% at the starting dose of 5 mg qd.
- •P1: Core laboratory confirmation of the following oHCM echocardiographic criteria at screening: Left ventricular (LV) hypertrophy with nondilated LV chamber in the absence of other cardiac disease. LV end -diastolic wall thickness that meets a threshold of: Z-score (Ommen 2020) > 2.5 in the absence of family history or Z-score (Ommen 2020) > 2 in the presence of positive family history or positive genetic test. LVEF ≥ 60% AND Valsalva LVOT-G ≥ 50 mmHg.
- •P1: oHCM of sarcomeric origin confirmed by genetic testing or, if unable to confirm by genetic testing, oHCM of sarcomeric origin may be presumed in the absence of history of metabolic disorders, mitochondrial cardiomyopathies, neuromuscular disease, malformation syndromes, infiltrative diseases/inflammation, and endocrine disorders (such as Fabry’s disease, Noonan syndrome with left ventricular hypertrophy, and amyloid-cardiomyopathy).
- •P1: New York Heart Association (NYHA) Class ≥ II at screening.
- •P1: Adequate acoustic windows for echocardiography.
- •P1: Participants on beta blockers, verapamil, diltiazem, or disopyramide should have been on stable doses or more than 4 weeks prior to randomization.
- •P2: Completed Period
- •If unable to complete Period 1 due to circumstances not related to compliance or safety, the Medical Monitor may review and determine eligibility.
- •P2: LVEF ≥ 55% after washout.
排除标准
- •P1: Significant valvular heart disease. - Moderate or severe valvular aortic stenosis or fixed subaortic obstruction. - Mitral regurgitation that is greater than mild in severity and not due to systolic anterior motion of the mitral valve (per judgment of Principal Investigator or designee). - Evidence of fixed left-sided obstruction (eg, subaortic, aortic valve, or coarctation of the aorta).
- •P1: Has received prior treatment with aficamten or mavacamten.
- •P1: Currently listed for heart transplantation or anticipated to be listed for heart transplantation in the next 12 months.
- •P1: Does not assent/consent to participate in the CMR substudy.
- •P1: Inability to tolerate CMR.
- •P1: Has an ICD or cardiac pacemaker.
- •P1: History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course.
- •P1: History of congenital heart disease other than oHCM (may be enrolled if not hemodynamically significant in the judgement of the Principal Investigator and study Medical Monitor).
- •P1: Hypersensitivity to aficamten or any of the excipients
- •P1: Has been treated with SRT (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the trial period.
- •P1: History of paroxysmal or persistent atrial fibrillation or atrial flutter.
- •P1: History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia within 3 months prior to screening.
- •P1: History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the Principal Investigator (or designee) or the Medical Monitor, would pose a risk to participant safety or interfere with the trial evaluation, procedures, or completion.
- •P1: Current or previous use of drugs known to cause cardiomyopathy (eg, anthracyclines, monoclonal antibodies [trastuzumab], alkylating agents [cyclophosphamide], and tyrosine kinase inhibitors [sunitinib and imatinib]).
- •P1: Currently participating in another investigational device or drug trial or received an investigational device or drug < 1 month (or 5 half-lives for drugs, whichever is longer) prior to screening.
- •P2: Had a confirmed LVEF < 40% with an associated dose interruption during participation in Period 1
- •P1: Implantable cardioverter defibrillator (ICD) implantation within 6 weeks of screening or planned ICD implantation during the trial period.
结局指标
主要结局
P1: Change in Valsalva LVOT-G while maintaining LVEF ≥ 55% from baseline to Week 12
P1: Change in Valsalva LVOT-G while maintaining LVEF ≥ 55% from baseline to Week 12
P2: Participant incidence of AEs and SAEs through End of Study
P2: Participant incidence of AEs and SAEs through End of Study
次要结局
- P1: Change in resting LVOT-G from baseline to Week 12
- P1: All participants: Observed Ctrough of aficamten over the 12-week treatment period Intensive PK substudy: Observed Cmax, tmax, AUCtau, and Ctrough for aficamten
- P1: Change in NT-proBNP from baseline to Week 12 Change in hs-cTnI from baseline to Week 12
- P1: Change in NYHA Functional Class from baseline to Week 12
- P1: Proportion of participants with ≥ 1 class improvement in NYHA Functional Class from baseline to Week 12
- P2: Change in the following measurements at 12-week intervals from Week 14 (baseline in OLE) through end of treatment: − Peak LVOT-G at rest and with Valsalva provocation
- P2: Change in the following measurements at 12-week intervals from Week 14 (baseline in OLE) through end of treatment: Proportion of participants with resting LVOT-G < 30 mmHg
- P2: Change in the following measurements at 12-week intervals from Week 14 (baseline in OLE) through end of treatment: − Proportion of participants with Valsalva LVOT-G < 50 mmHg
- P2: Change in the following measurements at 12-week intervals from Week 14 (baseline in OLE) through end of treatment: − Proportion of participants with Valsalva LVOT-G < 30 mmHg
- P2: Change in the following measurements at 12-week intervals from Week 14 (baseline in OLE) through end of treatment: − Proportion of participants with LVEF ≥ 50%, resting LVOT-G < 30 mmHg, and Valsalva LVOT-G < 50 mmHg
- P2: Time to the following event through last follow-up: − First resting LVOT-G < 30 mmHg − First Valsalva LVOT-G < 50 mmHg − First Valsalva LVOT-G < 30 mmHg − First LVEF ≥ 50%, resting LVOT-G < 30 mmHg, and Valsalva LVOT-G < 50 mmHg
- P2: Change in NYHA Functional Class from Week 14 to end of treatment
- P2: Proportion of participants with ≥ 1 class improvement in NYHA Functional Class from Week 14 to end of treatment
研究者
Cytokinetics Inc. Medical Affairs
Scientific
Cytokinetics Inc.
研究点 (2)
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