A Multicenter, Double-blind, Placebo-controlled Phase 3 Study Assessing the Safety and Efficacy of Selexipag on Morbidity and Mortality in Patients With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,156
- 试验地点
- 182
- 主要终点
- Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake
研究概览
简要总结
The AC-065A302 (GRIPHON) study is an event-driven Phase 3 study to demonstrate the effect of selexipag on time to first morbidity or mortality event in patients with pulmonary arterial hypertension.
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)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients 18-75 years old, with symptomatic PAH
- •PAH belonging to the following subgroups of the updated Dana Point Clinical Classification Group 1 (Idiopathic, or Heritable, or Drug or toxin induced, or Associated (APAH) with Connective tissue disease, Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair, or HIV infection)
- •Documented hemodynamic diagnosis of PAH by right heart catheterization, performed at any time prior to Screening
- •Six minute walk distance (6MWD) between 50 and 450 m at Screening within 2 weeks prior to the Baseline Visit
- •Signed informed consent
排除标准
- •Patients with pulmonary hypertension (PH) in the Updated Dana Point Classification Groups 2-5, and PAH Group 1 subgroups that are not covered by the inclusion criteria
- •Patients who have received prostacyclin or its analogs within 1 month before Baseline Visit, or are scheduled to receive any of these compounds during the trial
- •Patients with moderate or severe obstructive lung disease
- •Patients with moderate or severe restrictive lung disease
- •Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
- •Patients with documented left ventricular dysfunction
- •Patients with severe renal insufficiency
- •Patients with BMI <18.5 Kg/m2
- •Patients who are receiving or have been receiving any investigational drugs within 1 month before the Baseline Visit
- •Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6MWT
- •Recently conducted or planned cardio-pulmonary rehabilitation program based on exercise training
- •Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
- •Life expectancy less than 12 months
- •Females who are lactating or pregnant or plan to become pregnant during the study
- •Known hypersensitivity to any of the excipients of the drug formulations
研究组 & 干预措施
2
Matching placebo is administered orally with a dosing interval of approximately12 h. A (mock) up-titration scheme is followed
干预措施: Placebo (Drug)
1
Selexipag is up-titrated from Day 1 to Week 12 to each patient's maximum tolerated dose in the range of 200-1600 µg twice a day (b.i.d.) in 200 µg steps starting with one 200 µg oral tablet on Day 1. From Day 2 onwards, a b.i.d. dose regimen with an interval of approximately 12 hours is followed. If this dose (selexipag 200 μg b.i.d.) is well-tolerated, selexipag is up-titrated with weekly increments of 200 µg. Up-titration is followed by a stable maintenance treatment period from Week 12 onwards, up to Week 26, at the maximum tolerated dose
干预措施: Selexipag (Drug)
结局指标
主要结局
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake
时间窗: Up to 7 days after end of double-blind treatment (maximum: 4.3 years)
Time from randomization to the first occurrence of a morbidity event or death (all causes) was analyzed with the Kaplan-Meier method (event-free KM estimates at different time points). Morbidity event was defined as any of the following events confirmed by the Critical Event committee: * Hospitalization for worsening of pulmonary arterial hypertension (PAH), * Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy, * Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to worsening of PAH, * Disease progression which was defined by a decrease in 6-minute walk distance from baseline (\>=15%, confirmed by a 2nd test on a different day) combined with worsening of WHO FC for patients belonging to WHO FC II/III at baseline, or combined with the need for additional PAH-specific therapy for patients belonging to WHO FC III/IV at baseline. Note: The number of patients at risk decreased over time but this cannot be captured below
次要结局
- Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough(Week 26)
- Absence of Worsening From Baseline to Week 26 in Modified NYHA/WHO Functional Class (WHO FC)(Week 26)