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
Overview
- Phase
- Phase 1
- Intervention
- Pirfenidone
- Conditions
- Idiopathic Pulmonary Fibrosis
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 21
- Locations
- 15
- Primary Endpoint
- Percentage of Participants with Discontinuation of Any Study Medication Due to a Drug-Related Adverse Event
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Pirfenidone
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.
Intervention: Vismodegib
Outcomes
Primary Outcomes
Percentage of Participants with Discontinuation of Any Study Medication Due to a Drug-Related Adverse Event
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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))