Clinical trial NCT02648048: A Study of Oral Vismodegib in Combination With Pirfenidone in Participants With Idiopathic Pulmonary Fibrosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic Pulmonary Fibrosis
Vismodegib
Pirfenidone
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-01-06
Enrollment: 21
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants with Serious and Non-Serious Adverse Events
timeFrame: Baseline up to 28 weeks
measure: Percentage of Participants with Discontinuation of Any Study Medication Due to a Drug-Related Adverse Event
timeFrame: Baseline up to 28 weeks
measure: Percentage of Participants with Dose Modifications Due to Laboratory Abnormalities and Adverse Events
timeFrame: Baseline up to 28 weeks
measure: Percentage of Participants with Clinically Meaningful Laboratory Abnormalities as Assessed by Investigator
timeFrame: Baseline up to 28 weeks
Secondary outcomes:
measure: Total and Free Trough Plasma Concentrations of Vismodegib at Week 4 (Cmin, Wk4)
timeFrame: Predose (0 hour) at Week 4
measure: Total and Free Trough Plasma Concentrations of Vismodegib at Week 12 (Cmin, Wk12)
timeFrame: Predose (0 hour) at Week 12
measure: Total and Free Trough Plasma Concentrations of Vismodegib at Week 24 (Cmin, Wk24)
timeFrame: Predose (0 hour) at Week 24
measure: Total and Free Trough Plasma Concentrations of Vismodegib at Safety Follow-up Visit (Cmin, SFU)
timeFrame: At Day 30 post last dose (last dose = 24 weeks) (up to 28 weeks)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Elk Grove
country: United States
facility: Suburban Lung Associates
state: Illinois
city: Muncie
country: United States
facility: Medical Consultants, PC ; Pulmonary
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Medical School
state: Louisiana
city: Boston
country: United States
facility: Steward St. Elizabeth's Medical Center ; Pulmonary, Critical Care and Sleep Medicine
state: Massachusetts
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Reno
country: United States
facility: Allied Clinical Research
state: Nevada
city: Summit
country: United States
facility: Atlantic Respiratory Institute
state: New Jersey
city: Greensboro
country: United States
facility: Pulmonix LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Everett
country: United States
facility: Western Washington Medical Group
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Hannover
country: Germany
facility: Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Prasse A, Ramaswamy M, Mohan S, Pan L, Kenwright A, Neighbors M, Belloni P, LaCamera PP. A Phase 1b Study of Vismodegib with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. Pulm Ther. 2019 Dec;5(2):151-163. doi: 10.1007/s41030-019-0096-8. Epub 2019 Jul 19.