A Subject-, Investigator-, and Sponsor-blinded, Randomized, Placebo-controlled, Multicenter Study to Investigate Efficacy, Safety, and Tolerability of VAY736 in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).
研究概览
简要总结
The purpose of this study was to investigate the safety, tolerability and efficacy of VAY736 as potential therapy for the treatment of idiopathic pulmonary fibrosis (IPF).
详细描述
This was an exploratory (non-confirmatory) randomized, patient-, investigator-, sponsor- blinded, placebo controlled study of VAY736 in IPF patients. This study investigated the safety and efficacy of 300 mg VAY736 administered subcutaneously (s.c.) every 4 weeks for 48 weeks.
Participants were randomized in a 1:1 ratio on top of local standard of care (SOC), to receive VAY736 or placebo. Randomized subjects entered the treatment epoch (for up to 48 weeks), followed by two follow-up epochs: the PK/safety follow-up epoch and the PD/safety follow-up epoch. The PK/safety follow-up epoch lasted for 20 weeks. When the PK/safety follow-up epoch was completed, participants in the placebo arm were discharged from the study; but participants in the active arm (those who had received VAY736) continued into the PD/safety follow-up epoch. Participants in the PD/safety follow-up epoch were followed until B-cell recovery (in the peripheral blood), defined as: B cells >=50/μL or B cells >= 80% of baseline (whichever occurred first). If a participant had not recovered his/her B-cells after a period of 2 years from the last dose of VAY736, then this participant was discharged from the study.
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
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of definite or probable IPF within 5 years of the screening visit
- •Forced Vital Capacity (FVC) 40-90% predicted (inclusive)
- •Diffusing Capacity of the Lungs (DLCO), corrected for hemoglobin, 25-79% predicted (inclusive)
- •Forced Expiratory Volume in first second (FEV1)/FVC >70%
- •Unlikely to die from cause other than IPF within the next 3 years, in the opinion of the investigator
- •Unlikely to undergo lung transplantation during this trial
排除标准
- •Emphysema > fibrosis on screening high-resolution computed tomography (must be confirmed by central reader)
- •History of major organ, hematopoietic stem cell or bone marrow transplant
- •Clinically diagnosed acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) or other significant clinical worsening within 3 months of randomization
- •New York Heart Association (NYHA) class III/IV Congestive Heart Failure (CHF), Ejection Fraction (EF) <25%
- •Current smoker
- •Prior use of any B-cell depleting therapy (e.g., rituximab, ofatumumab, or other anti-CD20 mAb, anti-CD40, anti-CD19,anti-CD22 mAb, anti-CD52 mAb, or anti-BAFF mAb)
研究组 & 干预措施
VAY736
Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
干预措施: VAY736 (Drug)
VAY736
Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
干预措施: Standard of Care (SoC) (Drug)
Placebo
Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
干预措施: Placebo (Drug)
Placebo
Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
干预措施: Standard of Care (SoC) (Drug)
结局指标
主要结局
Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).
时间窗: From baseline up to 48 weeks post first dose of study treatment
FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
次要结局
- Percentage of Participants With All-cause Mortality Events(Up to 48 weeks post first dose of study treatment)
- Percentage of Participants With Progression-free Survival (PFS) Events(Up to 48 weeks post first dose of study treatment)
- Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events(Up to 48 weeks post first dose of study treatment)
- Percentage of Participants With Disease Progression Events(Up to 48 weeks post first dose of study treatment)
- Percentage of Participants With Composite Events(Up to 48 weeks post first dose of study treatment)
- Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs(From baseline up to 48 weeks post first dose of study treatment)
- Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air)(From baseline up to 48 weeks post first dose of study treatment)
- Number of Participants With Positive Serum Anti-VAY736 Antibodies(Day 1, 29, 85, 169, 253 and 337)
- Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD)(From baseline up to 48 weeks post first dose of study treatment)
- Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product(From baseline up to 48 weeks post first dose of study treatment)
- Ctrough of VAY736 From the Serum Concentration-time Data(At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337)