A Randomized, Phase 2, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (TROPOS Study)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 113
- 试验地点
- 110
- 主要终点
- Change from Baseline in PVR (Pulmonary Vascular Resistance)
研究概览
简要总结
Study KER-012-A201 is Phase 2, double-blind, randomized, placebo-controlled study to determine the efficacy and safety of KER-012 compared to Placebo in adults with PAH (WHO Group 1 PH) on stable background PAH therapy. The study is divided into the Screening Period, Treatment Period, Extension Period, and Follow-Up Period.
详细描述
This is a randomized, phase 2, double-blind, placebo-controlled study of KER-012 in combination with background therapy in participants with PAH of World Health Organization (WHO) Group 1, functional class II-III. Participants will be randomly assigned in a 2:2:2:3 ratio to receive KER-012 (Dose A), KER-012 (Dose B), KER-012 (Dose C), or placebo by subcutaneous injection (SC) every 4 weeks for a period of 24 weeks in the placebo-controlled treatment period of the study while on background therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and safety parameters. Participants who have not discontinued early from the placebo-controlled treatment period and have had their post-treatment period PVR assessment will be able to continue into the 72-week extension period in which KER-012 treated participants will continue to receive their same assigned dose level from the treatment period every 4 weeks and placebo treated participants will receive KER-012 (Dose B) every 4 weeks while on background therapy.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study in which treatment assignment will be blinded for the Investigators and any personnel (other than the unblinded pharmacist or designee) involved with the study conduct or evaluation at the investigational sites, the CRO, and the Sponsor.
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
- •Adult participants ≥ 18 years of age
- •Symptomatic World Health Organization (WHO) Group 1 Pulmonary Hypertension (PH)(PAH) classified by one of the following subgroups:
- •Idiopathic pulmonary arterial hypertension (IPAH);
- •Heritable pulmonary arterial hypertension (HPAH);
- •Associated with drugs and toxins;
- •PAH associated with:
- •Connective tissue disease
- •Congenital systemic-pulmonary intracardiac shunt
- •Has the following hemodynamic parameters that are consistent with the diagnosis of PAH:
- •Mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, AND
- •Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, AND
- •PVR ≥ 5 Wood Units (400 dyn·sec·cm-5)
- •Has WHO/New York Heart Association (NYHA) Functional Class (FC) II or III symptoms as assessed by the Investigator
- •Must be on a stable PAH background therapy with either an endothelin-receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE5-I) or soluble guanylate cyclase (sGC) stimulator and/or prostacyclin analogue or receptor agonist (oral/inhaled/SC/intravenous)
- •6MWD ≥ 150 and ≤ 500 meters at screening
- •Provide written (signed and dated) informed consent form before the initiation of any Screening tests or procedures
排除标准
- •Evidence or history of left ventricular dysfunction and/or clinically significant cardiac disease
- •Has pulmonary function tests (PFTs) with evidence of significant obstructive or parenchymal lung disease
- •Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or other local standard of care diagnostic evaluation at the time of PAH diagnosis or after
- •Has uncontrolled systemic hypertension
- •Hemoglobin < 9 g/dL at Screening
- •Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of < 12 months per Investigator assessment
- •Diagnosis of pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis
- •Initiation or discontinuation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Baseline or planned initiation during the study
- •Prior participation in a KER-012 study or prior treatment with a therapy targeting TGF-β superfamily (e.g. sotatercept)
- •Prior participation in another interventional clinical study with medicinal products within 30 days or 5 half-lives prior to Screening, whichever is longer
研究组 & 干预措施
Arm 1
KER-012 (Dose A) subcutaneously (SC) (every 4 weeks [Q4W]) Treatment Period: Dose A for 24 weeks; Extension Period: Dose A for another 72 weeks
干预措施: Dose A KER-012 (Biological)
Arm 2
KER-012 (Dose B) SC (Q4W) Treatment Period: Dose B for 24 weeks; Extension Period: Dose B for another 72 weeks
干预措施: Dose B KER-012 (Biological)
Arm 3
KER-012 (Dose C) SC (Q4W) Treatment Period: Dose C for 24 weeks; Extension Period: Dose C for another 72 weeks
干预措施: Dose C KER-012 (Biological)
Arm 4
Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks
干预措施: Dose B KER-012 (Biological)
Arm 4
Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks
干预措施: Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks (Biological)
结局指标
主要结局
Change from Baseline in PVR (Pulmonary Vascular Resistance)
时间窗: Baseline and Week 24
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background pulmonary arterial hypertension (PAH) therapy
Change From Baseline in PVR (Pulmonary Vascular Resistance)
时间窗: Baseline and Week 24
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background pulmonary arterial hypertension (PAH) therapy
次要结局
- Change from baseline in QTcF intervals(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Evaluate the changes from baseline in the concentration of the PAH biomarker, NT-proBNP in blood samples(Up to week 24 (primary treatment period) and up to Week 96 (extension period))
- Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- mPAP(Up to week 24 (primary treatment period) and up to Week 96 (extension period))
- Incidence of treatment-emergent adverse events (TEAEs)(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- CO(Up to week 24 (primary treatment period) and up to Week 96 (extension period))
- Evaluate improvement in functional assessment of KER-012 compared to Placebo in participants on background PAH therapy(Up to week 24 (primary treatment period) and up to Week 96 (extension period))
- Change from Baseline in the 6MWD(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Incidence of Antidrug Antibodies (ADA)(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- PAWP(Up to week 24 (primary treatment period) and up to Week 96 (extension period))
- Number of treatment-related TEAEs(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Number of discontinuations due to TEAEs(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Change from baseline in Systolic and Diastolic Blood Pressure(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Population PK predicted maximum concentration (Cmax) of KER-012(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Population PK predicted Area under concentration curve (AUC) of KER-012(Through week 24 (primary treatment period) and Through week 96 (extension period))
- Number of participants who experienced events indicative of clinical worsening of pulmonary arterial hypertension (PAH)(Up to week 24 (primary treatment period) and up to Week 96 (extension period))
- Evaluate improvement in risk stratifications of KER-012 in participants on background PAH therapy(Up to week 24 (primary treatment period) and up to Week 96 (extension period))
- Change From Baseline in the 6MWD(Through week 24 (primary treatment period))
- Evaluate Improvement in Functional Assessment of KER-012 Compared to Placebo in Participants on Background PAH Therapy(Up to week 24 (primary treatment period))
- Evaluate the Changes From Baseline in the Concentration of the PAH Biomarker, NT-proBNP in Blood Samples(Up to week 24 (primary treatment period))