NCT03439514终止3 期
A Phase 3, Multinational, Randomized, Placebo-controlled Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation (REALM-DCM)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 77
- 试验地点
- 103
- 主要终点
- Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a mutation of the gene encoding the lamin A/C protein (LMNA). The study will further evaluate a dose level of study drug (ARRY-371797) that has shown preliminary efficacy and safety in this patient population. After the primary analysis has been performed, eligible patients may receive open-label treatment with ARRY-371797.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
During the randomized, double-blind period, patients, Investigators, site personnel and the sponsor personnel directly involved with the conduct of the study will remain blinded to assigned treatment, except for regulatory reporting requirements.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with symptomatic lamin A/C protein (LMNA)-related cardiomyopathy Class II/III/ or Class IV defined as:
- •Gene positive for a pathogenic, likely pathogenic, or VUS mutation in the LMNA gene as determined by an accredited clinical laboratory.
- •Evidence of cardiac impairment in LVEF <= 50%
- •Patient will have an implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (ICD/CRT-D). ICD implanted at least 4 weeks prior to initiation of study treatment or CRT-D initiated at least 6 months prior to initiation of study treatment and defibrillation function activated at least 4 weeks prior to initiation of study treatment.
- •Class II/III patients must have objective functional impairment evidenced by a reduction in 6-minute walk test (6MWT); a. Screening: 6MWT distance >100 m but ≤450 m, AND b. Day -1 visit: 6MWT distance >100 m but ≤485 m, AND c. Baseline visit (Day 1): 6MWT distance >100 m but ≤485
- •Class II/III patients must be stable for at least 3 months
- •Stable medical and/or device therapy consistent with regional American Heart Association (AHA) / American College of Cardiology (ACC) or European Society of Cardiology (ESC) guidelines at the investigator discretion, without change in heart failure drug(s) dose in the past 1 month.
- •Patients must meet acceptable hematology, hepatic and renal laboratory values within 35 days prior to Day 1 as specified in the protocol.
- •Selected Key
排除标准
- •Presence of other form(s) of cardiomyopathy contributing to HF (eg, inflammatory or infiltrative cardiomyopathy), clinically significant cardiac anatomic abnormality (eg,LV aneurysm), clinically significant coronary artery disease (eg, coronary revascularization, exercise induced angina) or uncorrected, hemodynamically significant (ie, moderate-severe) primary structural valvular disease not due to HF, per investigator judgment.
- •Currently receiving intermittent or continuous IV inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation. Participants listed for cardiac transplantation may be enrolled provided transplantation is not likely to occur in the next 6 months.
- •Myocardial infarction, cardiac surgical procedures (other than for pacemaker/ICD/CRT-D implantation or replacement), acute coronary syndrome, serious systemic infection with evidence of septicemia, or any major surgical procedure requiring general anesthesia within 3 months prior to screening.
- •Currently receiving or deemed at high risk of requiring chronic renal replacement therapy (eg, hemodialysis or peritoneal dialysis) within 6 months.
- •Initiation of CRT within 6 months prior to screening.
- •Treatment with any investigational agent(s) for HF within 35 days prior to Day
- •Malignancy that is active or has been diagnosed within 3 years prior to screening, except surgically curatively resected in situ malignancies or surgically cured early breast cancer, prostate cancer, skin cancer (basal cell carcinoma, squamous cell carcinoma), thyroid cancer, or cervical cancer, or, with prior review by the medical monitor, other early stage surgically curatively resected malignancies with less than a 20% expected 2 year recurrence rate.
- •Non-cardiac condition that limits lifespan to < 1 year.
- •Serum positive for hepatitis B surface antigen, viremic hepatitis C, or human immunodeficiency virus (HIV) at screening.
研究组 & 干预措施
Part 2 Open-label Treatment
Experimental
ARRY-371797 (PF-07265803) tablet orally
干预措施: ARRY-371797 (PF-07265803) (Drug)
Part 1 Double-blind Treatment
Experimental
ARRY-371797 (PF-07265803) tablet orally OR matching placebo tablet orally
干预措施: ARRY-371797 (PF-07265803) (Drug)
Part 1 Double-blind Treatment
Experimental
ARRY-371797 (PF-07265803) tablet orally OR matching placebo tablet orally
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24
时间窗: Baseline, Week 24
The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional. Study discontinuation \& death were incorporated into endpoint definition through ranking in hypothesis testing of treatment difference. Missing data resulting from study discontinuation were imputed using control-based multiple imputation method to estimate treatment effect.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity(Maximum up to 212.28 weeks (maximum exposure was of 208 weeks))
- Number of Participants With Laboratory Test Abnormalities(Maximum up to 212.28 weeks (maximum exposure was of 208 weeks))
- Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24(Week 12, Week 24)
- Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24(Baseline, Week 4, Week 12, Week 24)
- Composite Time to First Occurrence of All-Cause Mortality or Worsening Heart Failure (WHF)(Maximum up to 212.28 weeks (maximum exposure was 208 weeks))
- Overall Survival (OS)(From randomization up to death due to any cause or censored date, maximum up to 212.28 weeks (maximum exposure was of 208 weeks))
- Change From Baseline in 6 MWT at Weeks 4 and 12(Baseline, Week 4, Week 12)
- Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24(Baseline, Week 12, Week 24)
- Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24(Week 12, Week 24)
- Number of Participants According to Categorization of Abnormal Vital Signs(Maximum up to 212.28 weeks (maximum exposure was of 208 weeks))
- Number of Participants According to Categorization of Electrocardiogram (ECG) Data(Maximum up to 212.28 weeks (maximum exposure was of 208 weeks))
- Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias(Baseline, Week 12, Week 24)
研究者
研究点 (103)
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