A Single Arm, Multicenter, Open-label, Phase 1b Study to Assess the Safety and Tolerability of Oral Vismodegib in Combination With Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 15
- 主要终点
- Percentage of Participants with Discontinuation of Any Study Medication Due to a Drug-Related Adverse Event
研究概览
简要总结
This is a single arm, multicenter, open-label, Phase 1b study to evaluate the safety and tolerability of vismodegib in combination with pirfenidone in participants with idiopathic pulmonary fibrosis (IPF) currently being treated with pirfenidone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Have a diagnosis of IPF 5 years from time of screening, confirmed at baseline
- •Tolerated dose of pirfenidone 1602-2403 mg once daily (QD) for a minimum of 24 weeks required prior to and during screening
- •Greater than or equal to (>=) 50 percent (%) and less than or equal to (<=) 100% of predicted forced vital capacity (FVC) at screening
- •Stable baseline lung function as evidenced by a difference of less than (<) 10% in absolute FVC measurements (in liters) between screening and Day 1/Visit 2 prior to enrollment
- •>=30% and <=90% of predicted diffusion capacity of the lung for carbon monoxide at screening
- •Agree to use protocol defined methods of contraception
- •Male participants must agree not to donate semen during the study and for at least 2 months (or as per local requirements) after the last dose of vismodegib
- •Agree not to donate blood or blood products during the study and for at least 9 months (or as per local requirements) after the last dose of study treatment
排除标准
- •Prior treatment with vismodegib or any Hh-pathway inhibitor
- •Evidence of other known causes of interstitial lung disease
- •Hospitalization due to an exacerbation of IPF within 4 weeks prior to or during screening
- •Lung transplant expected within 6 months of screening
- •Evidence of clinically significant lung disease other than IPF
- •Post-bronchodilator forced expiratory volume in 1 second/FVC ratio <0.7 at screening
- •Any clinically significant medical disease (other than IPF) that is associated with an expected survival of <6 months, likely to require a change in therapy during the study
- •Class IV New York Heart Association chronic heart failure or historical evidence of left ventricular ejection fraction <35%
- •Known current malignancy or current evaluation for a potential malignancy
- •Known immunodeficiency, including, but not limited to, human immunodeficiency virus infection
- •Evidence of acute or chronic hepatitis or known liver cirrhosis
- •Creatinine clearance <=30 milliliter per minute, calculated using the Cockcroft-Gault formula
研究组 & 干预措施
Vismodegib and Pirfenidone
Participants being treated with pirfenidone, will receive vismodegib 150 milligrams (mg) once daily and pirfenidone up to 2403 mg daily orally for 24 weeks.
干预措施: Pirfenidone (Drug)
Vismodegib and Pirfenidone
Participants being treated with pirfenidone, will receive vismodegib 150 milligrams (mg) once daily and pirfenidone up to 2403 mg daily orally for 24 weeks.
干预措施: Vismodegib (Drug)
结局指标
主要结局
Percentage of Participants with Discontinuation of Any Study Medication Due to a Drug-Related Adverse Event
时间窗: Baseline up to 28 weeks
An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possibility of causal relationship. Relatedness to the study drug will be assessed by the investigator.
Percentage of Participants with Clinically Meaningful Laboratory Abnormalities as Assessed by Investigator
时间窗: Baseline up to 28 weeks
Vital signs and laboratory parameters will be evaluated, and percentage of participants with any clinically meaningful abnormalities as assessed by Investigator will be reported. Laboratory abnormalities of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade greater than (\>) 3 will be considered clinical meaningful.
Percentage of Participants with Serious and Non-Serious Adverse Events
时间窗: Baseline up to 28 weeks
An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possibility of causal relationship. A serious adverse event is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Percentage of Participants with Dose Modifications Due to Laboratory Abnormalities and Adverse Events
时间窗: Baseline up to 28 weeks
An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possibility of causal relationship.
次要结局
- Total and Free Trough Plasma Concentrations of Vismodegib at Week 24 (Cmin, Wk24)(Predose (0 hour) at Week 24)
- Total and Free Trough Plasma Concentrations of Vismodegib at Week 4 (Cmin, Wk4)(Predose (0 hour) at Week 4)
- Total and Free Trough Plasma Concentrations of Vismodegib at Week 12 (Cmin, Wk12)(Predose (0 hour) at Week 12)
- Total and Free Trough Plasma Concentrations of Vismodegib at Safety Follow-up Visit (Cmin, SFU)(At Day 30 post last dose (last dose = 24 weeks) (up to 28 weeks))