A Study of Oral Vismodegib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

This is a randomized, multicenter, double-blind, placebo-controlled, parallel-group study of vismodegib in patients with IPF. Eligible patients will be randomized in a 2:1 ratio to one of two treatment arms: vismodegib or placebo. The duration of treatment will be 52 weeks. Study drug will be administered daily by the oral route. An 8-week safety follow-up period is included for all patients who receive at least one dose of study drug.

Study Overview

• Status: Withdrawn
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: placebo; Drug: vismodegib

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients aged >/=40 years at Visit 1
• Diagnosis of IPF within the previous 5 years from time of screening and confirmed at baseline
• Patients from countries where a treatment is licensed/approved for IPF must additionally meet at least one of the following criteria to be eligible: (1) be unable to access a licensed therapy for IPF; (2) treatment with a licensed therapy/therapies has been stopped for lack of efficacy or because of safety/tolerability reasons (a washout period will be required); (3) be unwilling to be treated with a licensed therapy and study enrollment considered appropriate.
• Forced vital capacity (FVC) >/=40% and </=90% of predicted at screening
• Stable baseline lung function as evidenced by a difference of <10% in absolute FVC measurements (in liters) between screening and Day 1/Visit 2 prior to randomization
• Diffusion capacity of the lung for carbon dioxide (DLCO) >/=25% of predicted at screening
• Adequate hematopoietic capacity, liver and renal function
• Female patients of childbearing potential must use two methods of acceptable contraception, including one highly effective method and a barrier method, during treatment and for 7 months after completion of study treatment (or as per local requirement)
• Male patients must agree to remain abstinent or use a condom, even after a vasectomy, during sexual intercourse with female partners while being treated with vismodegib/placebo, and for 2 months after completion of study treatment
• Agreement not to donate blood or blood products during the study and for at least 7 months (or as per local requirements) after the last dose of study treatment

Exclusion Criteria:

• Pregnant or lactating
• Known hypersensitivity to any of the study drug excipients or the drug itself
• 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 12 months of screening
• Evidence of clinically significant lung disease other than IPF
• Substantial emphysema on high resolution computed tomography (HRCT) with degree of emphysema greater than fibrosis
• Post bronchodilator forced expiratory volume in 1 second/FVC ratio <0.7 at screening
• 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 HIV infection
• Any clinically significant medical disease (other than IPF) that is associated with an expected survival of <12 months, likely to require a change in therapy during the study, or likely to impact the ability of the patient to participate in the study in the opinion of the investigator, or impact the study efficacy or safety assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; matching placebo administered daily orally
Experimental: Vismodegib	Drug: vismodegib; vismodegib 150 mg administered daily orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in forced vital capacity (FVC) percent predicted	From baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in diffusion capacity of the lung for carbon dioxide (DLCO)	From baseline to Week 52
Annualized rate of change in FVC	Week 52
Progression-free survival	Week 52
Time from randomization to first event of acute IPF exacerbation	Up to 52 weeks
Change in Quality of Life measurements	From baseline to Week 52
Safety: Incidence of adverse events (AEs)	Approximately 60 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: June 18, 2014
• First Submitted That Met QC Criteria: June 18, 2014
• First Posted (Estimate): June 20, 2014

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: GB29298; 2014-000963-42 (EudraCT Number)