2023-509141-12-00招募中2 期
Phase 2, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of Sotatercept versus Placebo-Controlled for the Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) due to Heart Failure with Preserved Ejection Fraction (HFpEF)
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 174
- 试验地点
- 33
- 主要终点
- Change from baseline in PVR at Week 24
研究概览
简要总结
Efficacy: This study is designed to evaluate the efficacy, measured by change from baseline in PVR (primary endpoint) and 6MWD (key secondary endpoint) of sotatercept versus placebo in adults with Cpc-PH due to HFpEF. Safety: The safety and tolerability of sotatercept versus placebo in adults with Cpc-PH due to HFpEF will be assessed by the safety endpoints listed below.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 主要目的
- The Follow-up Period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age 18 to 85 years
- •Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study
- •Ability to understand and provide documented informed consent for participation
- •Clinical diagnosis of HFpEF: • Left ventricular ejection fraction ≥ 50%, with no history of LVEF below 45% in more than 2 consecutive measurements under stable conditions
- •Demonstrated Cpc-PH by all of the following: • Baseline RHC performed within 28 days of randomization documenting a minimum PVR ≥ 320 dyn•sec/cm5 (4 wood units) (see Section 9.2.1 for historic RHC requirements) • Mean pulmonary arterial pressure > 20 mmHg • Pulmonary capillary wedge pressure > 15 mmHg but < 30 mmHg
- •New York Heart Association FC of II or III
- •Six minute Walk Distance ≥ 100 meters repeated twice during Screening and both values within 15% of each other, calculated from the highest value (see Section 9.3.2 for details)
- •Chronic medication for HF or for any underlying condition, administered at a stable (per investigator) dose for ≥ 30 days prior to Visit
- •Diuretics and/or anticoagulants are excepted from this rule but should not be newly started or stopped within 30 days of Visit 1, and a prescribed dose change should not occur within 7 days of Visit
- •Anticoagulation may be suspended for RHC if necessary.
- •Women of childbearing potential (defined in Appendix 2) must: • Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug • If sexually active, with a male partner: - Use highly effective contraception without interruption, for at least 28 days prior to starting the investigational product, AND - Agree to use the same highly effective contraception in combination with a barrier method during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment • Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study drug See Appendix 2 for additional contraceptive information.
- •Male participants must: • Agree to use a condom, defined as a male latex condom or non-latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a WOCBP while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy (see Appendix 2 for additional contraceptive information) • Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study drug
- •Ability to adhere to the study visit schedule and understand and comply with all protocol requirements
排除标准
- •Diagnosis of PH in WHO Group 1, 3, 4 or 5
- •Clinically significant, active lung disease: -COPD w/post-bronchodilator FEV1 < 60% predicted -Restrictive lung disease w/total lung capacity < 70% predicted -More than mild ILD w/FVC < 70% or FEV1 < 60% predicted (unless absence of > mild ILD, fibrosis, or COPD on CT imaging)
- •CV comorbidities, any: -Hx of more than mild mitral or aortic stenosis, corrected mitral or aortic stenosis by surgical or transcatheter method w/in 12 months of Visit 1 -Ongoing more than mild mitral or aortic regurg, corrected mitral or aortic regurg by surgical or transcatheter method w/in 12 months of Visit 1 -More than 1 valve replacement or repair or any anticipated valve replacement or repair -Severe tricuspid regurgitation due to primary valvular disease -MI, ACS, CABG or PCI w/in 180 days of Visit 1 -Hx of serious life-threatening or hemodynamically significant arrhythmia -Hx of or anticipated heart transplant or ventricular assist device implantation -Hx of implantable cardioverter defibrillator placement, anticipated pacemaker implant, or pacemaker implant w/in 30 days of Scrning -Hx of pericardial constriction, hypertrophic cardiomyopathy, sarcoidosis, or amyloid cardiomyopathy -Uncontrolled systemic hypertension (SBP > 160 mmHg or DBP > 110 mmHg during Scrning at rest) -Systemic hypotension (SBP < 90 mmHg or DBP < 50 mmHg during Scrning) -Resting HR < 45 bpm or > 115 bpm (including afib) -Stroke w/in 90 days of Visit 1 -Acutely decompensated HF requiring hospitalization w/in 30 days of Visit 1 -ECG during Scrning with QTcF > 470 msec if male, > 480 msec if female, or > 500 msec if ventricular conduction defect (RBBB/LBBBB or interventricular conduction delay) is present -Personal/family Hx of Brugada synd, sudden cardiac arrest or unexplained SCD or arrest -Personal/family Hx of long QT synd unless subject ECG shows normal QTcARVD unless recent cardiac MRI shows no evidence of diagnosis
- •Hospitalization for worsening of medical conditions/ significant surgery per PI w/in 30 days of Visit 1
- •Received any approved PAH-specific therapies (ERA, prostacyclin analogs, PDE-5 inhibitors, sGC stimulators) w/in 30 days of Visit
- •Oral PDE-5 inhibitor for ED permitted if not administered w/in 48 hours of visit or procedure.
- •Received IV inotropes w/in 30 days of Visit 1
- •Received EPOw/in 6 months of Visit 1
- •Hx of chronic liver disease, including untreated hepatitis B or C (with evidence of recent infection or active virus replication), with severe hepatic impairment or cirrhosis
- •Prior exposure to sotatercept or luspatercept
- •Currently enrolled in or completed IP study w/in 30 days for small-molecule drugs or w/in 5 halflives for biologics prior to documented consent date
- •Initiation of cardiopulm rehab exercise program w/in 90 days of Visit 1 or planned initiation during study
- •Lab values, any of: -Hgb > gender-specific ULN or < 10 g/dL per local lab w/in 28 days of Visit 1 -Serum ALT, AST, or total bilirubin > 3×ULN w/in 28 days of Visit 1 -eGFR < 30 mL/min/1.73 m2 (4-variable MDRD equation) w/in 28 days of Visit 1 or required renal replacement w/in 90 days of Visit 1 - HbA1c > 10% w/in 28 days of Visit 1 - PLT < 75,000/mm3 w/in 28 days of Visit 1
- •Hx of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product
- •Major surgery w/in 60 days of Visit 1 or incomplete recovery from any surgery prior to Visit 1
- •Prior solid organ or bone marrow transplant, or life expectancy of < 12 months
- •Pregnancy/ breastfeeding
- •Active malignancy, except fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
- •Hx of clinically significant (per investigator) disease that may limit study participation
- •BMI ≥ 50 kg/m2
- •More than mild OSA
- •Any non-cardiopul condition or impairment (except dyspnea) that limits ability to perform 6MWT
- •Polish translation (due to size limit)
研究组 & 干预措施
sotatercept
Experimental
Participants receiving sotatercept
干预措施: sotatercept (Drug)
结局指标
主要结局
Change from baseline in PVR at Week 24
Change from baseline in PVR at Week 24
次要结局
- Time to clinical worsening at Wk 24: −Hospitalization cardiopulmonary indication −Administration IV diuretics or SC furosemide −Death −Decrease 6MWD by ≥ 15% from baseline • Change from baseline in: -hemodynamic and ECHO parameters at Wk 24 -NT-proBNP at Wk 24 - -NYHA FC at Wk 24
- Cont. translations
研究者
Alexandra Cornell
Scientific
Acceleron Pharma Inc.
研究点 (33)
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