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

Idiopathic Pulmonary Fibrosis Clinical Trial

— ISLAND2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02648048
• Other study ID #: GB29764
• Secondary ID: 2015-003481-81
• Status: Completed
• Phase: Phase 1
• First received: January 5, 2016
• Last updated: October 26, 2017
• Start date: January 15, 2016
• Est. completion date: November 30, 2016

Study information

• Verified date: October 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 30, 2016
• Est. primary completion date: November 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Pirfenidone
Pirfenidone will be administered as per the dosage schedule mentioned in arm description.
• Vismodegib
Vismodegib will be administered as per the dosage schedule mentioned in arm description.

Locations

Country	Name	City	State
Germany	Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM	Hannover
United States	Steward St. Elizabeth's Medical Center ; Pulmonary, Critical Care and Sleep Medicine	Boston	Massachusetts
United States	Suburban Lung Associates	Elk Grove	Illinois
United States	Western Washington Medical Group	Everett	Washington
United States	Pulmonix LLC	Greensboro	North Carolina
United States	Scripps Clinic	La Jolla	California
United States	University of Louisville	Louisville	Kentucky
United States	Medical Consultants, PC ; Pulmonary	Muncie	Indiana
United States	Tulane University Medical School	New Orleans	Louisiana
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Central Florida Pulmonary Group, PA	Orlando	Florida
United States	Allied Clinical Research	Reno	Nevada
United States	Swedish Medical Center	Seattle	Washington
United States	Atlantic Respiratory Institute	Summit	New Jersey
United States	PMG Research of Wilmington	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)