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

NCT02648048 | Completed Phase 1

• 2 other identifiers: GB297642015-003481-81
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 15

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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Idiopathic Pulmonary Fibrosis; Vismodegib; Pirfenidone

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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 Week 24 (Cmin, Wk24)

  Predose (0 hour) at Week 24

• 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)

Study Arms (1)

Vismodegib and Pirfenidone

EXPERIMENTAL

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; Drug: Vismodegib

Interventions

Pirfenidone DRUG

Pirfenidone will be administered as per the dosage schedule mentioned in arm description.

Also known as: RO0220912

Vismodegib and Pirfenidone

Vismodegib DRUG

Vismodegib will be administered as per the dosage schedule mentioned in arm description.

Also known as: RO5450815

Vismodegib and Pirfenidone

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (15)

Scripps Clinic

La Jolla, California, 92037, United States

Location

Central Florida Pulmonary Group, PA

Orlando, Florida, 32803, United States

Location

Suburban Lung Associates

Elk Grove, Illinois, 60007, United States

Location

Medical Consultants, PC ; Pulmonary

Muncie, Indiana, 47303, United States

Location

University of Louisville

Louisville, Kentucky, 40202-1798, United States

Location

Tulane University Medical School

New Orleans, Louisiana, 70112, United States

Location

Steward St. Elizabeth's Medical Center ; Pulmonary, Critical Care and Sleep Medicine

Boston, Massachusetts, 02135, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68131, United States

Location

Allied Clinical Research

Reno, Nevada, 89503, United States

Location

Atlantic Respiratory Institute

Summit, New Jersey, 07901, United States

Location

Pulmonix LLC

Greensboro, North Carolina, 27403, United States

Location

PMG Research of Wilmington

Wilmington, North Carolina, 28401, United States

Location

Western Washington Medical Group

Everett, Washington, 98208, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM

Hanover, 30625, Germany

Location

Related Publications (1)

• 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.

  PMID: 32026407 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

pirfenidone; HhAntag691

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2016
• First Posted: January 6, 2016
• Study Start: January 15, 2016
• Primary Completion: November 30, 2016
• Study Completion: November 30, 2016
• Last Updated: October 30, 2017

Record last verified: 2017-10

Locations

DE (1); US (14)