A Study of Oral Vismodegib in Combination With Pirfenidone in Participants With Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Pirfenidone
* Drug: Vismodegib


Participation Criteria
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Eligibility Criteria
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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 Evidence of acute or chronic hepatitis or known liver cirrhosis Creatinine clearance <=30 milliliter per minute, calculated using the Cockcroft-Gault formula

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vismodegib and Pirfenidone<br>Participants being treated with pirfenidone, will receive vismodegib 150 milligrams (mg) once daily and pirfenidone up to 2403 mg daily orally for 24 weeks. | Drug: Pirfenidone<br>* Pirfenidone will be administered as per the dosage schedule mentioned in arm description.<br>* Other names: RO0220912;Drug: Vismodegib<br>* Vismodegib will be administered as per the dosage schedule mentioned in arm description.<br>* Other names: RO5450815;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Serious and Non-Serious Adverse Events | 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. | Baseline up to 28 weeks | 
| Percentage of Participants with Discontinuation of Any Study Medication Due to a Drug-Related Adverse Event | 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. | Baseline up to 28 weeks | 
| Percentage of Participants with Dose Modifications Due to Laboratory Abnormalities and Adverse Events | An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possibility of causal relationship. | Baseline up to 28 weeks | 
| Percentage of Participants with Clinically Meaningful Laboratory Abnormalities as Assessed by Investigator | 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. | Baseline up to 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total and Free Trough Plasma Concentrations of Vismodegib at Week 4 (Cmin, Wk4) | Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + alpha-1-acid glycoprotein (AAG)-bound vismodegib plasma concentration. | Predose (0 hour) at Week 4 | 
| Total and Free Trough Plasma Concentrations of Vismodegib at Week 12 (Cmin, Wk12) | Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + AAG-bound vismodegib plasma concentration. | Predose (0 hour) at Week 12 | 
| Total and Free Trough Plasma Concentrations of Vismodegib at Week 24 (Cmin, Wk24) | Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + AAG-bound vismodegib plasma concentration. | Predose (0 hour) at Week 24 | 
| Total and Free Trough Plasma Concentrations of Vismodegib at Safety Follow-up Visit (Cmin, SFU) | Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + AAG-bound vismodegib plasma concentration. | At Day 30 post last dose (last dose = 24 weeks) (up to 28 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic Pulmonary Fibrosis, Vismodegib, Pirfenidone