A Phase 2b Randomized, Double-blind, Placebo-controlled, Repeat-dose, Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 153
- 试验地点
- 82
- 主要终点
- Core Phase: Change in FVC % Predicted From Baseline to Week 52
研究概览
简要总结
HZNP-HZN-825-303 (HARBOR) comprises of 2 parts. Part 1 (Core Phase) is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial to evaluate the efficacy, safety and tolerability of HZN-825 in participants with Idiopathic Pulmonary Fibrosis (IPF).
Part 2 (Extension Phase) is an optional, open-label, repeat-dose, multicenter extension of the Core Phase. The trial will include up to an 8-week Screening Period and a 52-week Double-blind Treatment Period in the Core Phase and 52 weeks of open-label HZN-825 treatment in the Extension Phase.
During the Core Phase, participants will be screened within 8 weeks prior to the baseline (Day 1) Visit. Approximately 135 participants who meet the trial eligibility criteria will be randomly assigned in a 1:1:1 ratio on Day 1 to receive HZN-825 300 mg QD, HZN-825 300 mg BID or matching placebo orally for 52 weeks using the following 2 stratification factors:
- Concomitant use of approved IPF therapy (i.e., nintedanib or pirfenidone): yes or no
- Forced vital capacity (FVC) % predicted at Baseline: ≥70% or <70%
Participants who complete the 52-week Double blind Treatment Period of the Core Phase of the trial will be invited to extend their participation in the 52-week Extension Phase of the trial.
详细描述
Part 1 (Core Phase) The overall objective of the Core Phase is to investigate the efficacy, safety and tolerability of 2 dose regimens of HZN-825, a selective antagonist of lysophosphatidic acid receptor-1 (LPAR1), administered orally once daily (QD) or twice daily (BID) for 52 weeks in the treatment of participants with IPF.
Part 2 (Extension Phase) The overall objective of the Extension Phase is to investigate the long-term efficacy, safety and tolerability of HZN-825, a selective antagonist of LPAR1, administered at a dose of 300 mg BID orally to participants with IPF in a 52-week open-label extension (OLE) following completion of the Core Phase of the trial. The dose for the Extension Phase may be modified based on the results of the Core Phase.
Two types of Baseline are defined for the Extension Phase:
- OLE Baseline, defined as the latest measurement prior to the first dose of HZN-825 in the Extension Phase
- HZN-825 Baseline, defined as the latest measurement prior to the first dose of HZN-825 in either the Core Phase or the Extension Phase. For subjects who received placebo in the Core Phase, OLE Baseline will be the same as HZN-825 Baseline.
Acquired from Horizon in 2024
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
- Triple (Participant, Care Provider, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
HZN-825 300 mg once daily (QD)
Two 150 mg oral tablets given in the morning with a meal and two matching placebo tablets given in the evening with a meal; total daily dose 300 mg HZN-825.
干预措施: HZN-825 (Drug)
HZN-825-300 mg twice daily (BID)
Two 150 mg oral tablets given in the morning with a meal and two 150 mg oral tablets given in the evening with a meal; total daily dose 600 mg HZN-825.
干预措施: HZN-825 (Drug)
Placebo BID
Matching placebo tablets (2) given in the morning with a meal and matching placebo tablets (2) given in the evening with a meal; total dose 4 placebo tablets.
干预措施: Placebo (Drug)
结局指标
主要结局
Core Phase: Change in FVC % Predicted From Baseline to Week 52
时间窗: Baseline and Week 52
FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.
Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104
时间窗: OLE baseline (Week 52) and Week 104
OLE baseline was defined as the latest measurement prior to the first dose of HZN-825 in the extension phase. FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.
次要结局
- Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52(Baseline and Week 52)
- Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52(Baseline and Week 52)
- Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52(Baseline and Week 52)
- Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52(Baseline and Week 52)
- Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52(Baseline to Week 52)
- Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52(Up to Week 52)
- Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52(Up to Week 52)
- Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From 1st dose to last dose + 28 days, Median (min, max) duration was 12.0 (1.0, 13.1) months for Core Phase and 7.0 (1.6, 13.2) months for OLE Phase.)
- Core Phase: Pre- and Post-dose Concentrations of HZN-825(Day 1 (2-4 hours after the first dose), Week 4 (pre-dose), Week 10, Weeks 16 and 28 (pre-dose and 2-4 hours post-dose), and Weeks 40 and 52 (pre-dose for participants entering OLE).)