NCT04811092终止3 期

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy in Newly Diagnosed Intermediate- and High-risk PAH Patients

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA302 个研究点分布在 4 个国家目标入组 321 人开始时间: 2022年3月18日最近更新: 2026年6月8日

适应症

干预措施

试验速览

阶段: 3 期
状态: 终止
发起方
入组人数: 321
试验地点: 302
主要终点: Time to Clinical Worsening

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

The objective of this study is to evaluate the effects of sotatercept (MK-7962, formerly called ACE-011) treatment (plus background pulmonary arterial hypertension [PAH] therapy) versus placebo (plus background PAH therapy) on time to clinical worsening (TTCW) in participants who are newly diagnosed with PAH and are at intermediate or high-risk of disease progression.

详细描述

This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate sotatercept when added to background PAH therapy in newly diagnosed intermediate- or high risk PAH participants.

Participants enrolled in the study will have a diagnosis within 12 months of study screening of symptomatic PAH (World Health Organization [WHO] Group 1, classified as functional class [FC] II or III) and presentation of idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin- induced PAH, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects.

As of Amendment 11, this study will be closed so that all eligible participants can receive sotatercept either on the MK-7962-004 extension study (SOTERIA, NCT04796337) or by commercial access, if available. All eligible participants will complete the end of treatment visit before enrollment in the extension study or initiation of commercial product. Participants not enrolling into the extension study or initiating commercial product will complete the end of study visit.

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

Double-blind

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

•Inclusion criteria include but are not limited to:
•Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum pulmonary vascular resistance (PVR) of ≥ 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg, with the diagnosis of WHO PAH Group 1 in any of the following subtypes:
•Idiopathic PAH
•Heritable PAH
•Drug/toxin-induced PAH
•PAH associated with connective tissue disease
•PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
•Symptomatic PAH classified as World Health Organization (WHO) Functional Class (FC) II or III
•Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 6 or Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk or above)
•Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening
•Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value)
•Females of childbearing potential must meet the following criteria:
•Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing urine or serum 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, have used highly effective contraception without interruption, for at least 28 days prior to starting the investigational product AND agreed 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 treatment
•Male participants must meet the following criteria:
•Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential 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
•Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment

排除标准

•Exclusion Criteria include but are not limited to:
•Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5
•Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension, schistosomiasis-associated PAH, pulmonary veno occlusive disease, and pulmonary capillary hemangiomatosis
•Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
•Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after a period of rest
•Baseline systolic BP < 90 mmHg at screening
•Pregnant or breastfeeding women
•Any of the following clinical laboratory values at the Screening Visit:
•Estimated glomerular filtration rate < 30 mL/min/1.73 m^2 (as defined by The Modification of Diet in Renal Disease [MDRD] equation)
•Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels > 3 × ULN
•Platelet count < 50,000/mm^3 (< 50.0 × 10^9 /L)
•Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented informed consent
•Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept
•History of pneumonectomy
•Pulmonary function test values of forced vital capacity < 60% predicted within 1 year prior to the Screening Visit
•Stopped receiving any PH chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
•Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the Screening Visit or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible)
•Untreated more than mild obstructive sleep apnea
•History of known pericardial constriction
•History of restrictive or congestive cardiomyopathy
•History of atrial septostomy within 180 days prior to the Screening Visit
•Electrocardiogram with Fridericia's corrected QT interval > 500 ms during the Screening Period
•Personal or family history of long QT syndrome or sudden cardiac death
•Left ventricular ejection fraction < 50% on historical echocardiogram (ECHO) within 1 year prior to the Screening Visit
•Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) in the past 6 months prior to the Screening Visit
•Cerebrovascular accident within 3 months prior to the Screening Visit
•Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment
•Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
•Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and vasopressin) within 30 days prior to the Screening Visit
•Has an active malignancy with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently or expected, during the study, to be treated with radiation therapy, chemotherapy, and/or surgical intervention, or hormonal treatment

研究组 & 干预措施

Sotatercept plus background PAH therapy

Experimental

Participants received sotatercept at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, subcutaneously (SC) every 21 days plus background PAH therapy.

干预措施: Sotatercept (Drug)

结局指标

主要结局

Time to Clinical Worsening

时间窗: Up to ~36 months

Time to clinical worsening is defined as time from randomization to the first confirmed morbidity event or death. Clinical worsening events are defined as all-cause death, non-planned PAH-related hospitalization of ≥ 24 hours in duration, atrial septostomy, lung transplant and deterioration in performance in 6-minute walk test from baseline combined with one of the following conditions: worsening of WHO functional class from baseline, signs/symptoms of increased right heart failure, addition of a background PAH therapy or change in the background PAH therapy delivery route to parenteral. All events will be adjudicated by a blinded, independent committee of clinical experts.

次要结局

Percentage of Participants Achieving the Multicomponent Improvement Endpoint of 6-Minute Walk Distance (6MWD), N-terminal prohormone Btype natriuretic peptide (NT-ProBNP) and World Health Organization (WHO) Functional Class (FC)(Baseline and Week 24)
Percentage of Participants who Achieved a Low Registry to Evaluate Early and Long Term PAH Disease Management (REVEAL) Lite 2 Risk Score(Baseline and Week 24)
Percentage of Participants who Maintain or Achieve a Low Simplified French Risk Score(Baseline and Week 24)
Change from Baseline in NT-proBNP Levels(Baseline and Week 24)
Percentage of Participants who Improve in WHO FC or Maintain WHO FC II at 24 Weeks from Baseline(Baseline and Week 24)
Change from Baseline in 6MWD(Baseline and Week 24)
Overall Survival (OS)(Up to ~36 Months)
Change from Baseline in the Physical Impacts Domain Score of Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT)®(Baseline and Week 24)
Change from Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT®(Baseline and Week 24)
Change from Baseline in the Cognitive/Emotional Impacts Domain Score of PAH-SYMPACT®(Baseline and Week 24)
Number of Participants who Experience an Adverse Event (AE)(Up to ~36 Months)
Number of Participants who Discontinued Study Treatment due to AEs(Up to ~34 months)
Incidence of Anti-drug Antibodies (ADAs) to Sotatercept(Up to ~36 Months)

研究者

发起方

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

申办方类型

Industry

责任方

Sponsor

研究点 (302)

Loading locations...

相似试验

已完成

3 期

A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH)Pulmonary Arterial Hypertension

NCT04896008Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA173

已完成

3 期

A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (MK-7962-003/A011-11)(STELLAR)Pulmonary Arterial Hypertension

NCT04576988Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA324

已完成

2 期

A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PAH)Pulmonary Arterial Hypertension

NCT03496207Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA106

终止

2 期

To Determine Safe and Effective Dose of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Participants With Advanced Non-small Cell Lung CancerCarcinoma, Non-Small-Cell LungCarcinoma, Small-Cell LungCancer of Head and NeckUterine Cervical CancerBladder CancerAnemia

NCT01284348Merck Sharp & Dohme LLC26

已完成

3 期

Efficacy and Safety of Suvorexant (MK-4305) for Reducing Incidence of Delirium in Japanese Participants at High Risk of Delirium (MK-4305-085)Delirium

NCT04571944Merck Sharp & Dohme LLC207