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A Study of Oral Vismodegib in Combination With Pirfenidone in Participants With Idiopathic Pulmonary Fibrosis (ISLAND2)

Primary Purpose

Idiopathic Pulmonary Fibrosis

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Pirfenidone
Vismodegib
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis focused on measuring Idiopathic Pulmonary Fibrosis, Vismodegib, Pirfenidone

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Scripps Clinic
  • Central Florida Pulmonary Group, PA
  • Suburban Lung Associates
  • Medical Consultants, PC ; Pulmonary
  • University of Louisville
  • Tulane University Medical School
  • Steward St. Elizabeth's Medical Center ; Pulmonary, Critical Care and Sleep Medicine
  • Creighton University Medical Center
  • Allied Clinical Research
  • Atlantic Respiratory Institute
  • Pulmonix LLC
  • PMG Research of Wilmington
  • Western Washington Medical Group
  • Swedish Medical Center
  • Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vismodegib and Pirfenidone

Arm Description

Participants being treated with pirfenidone, will receive vismodegib 150 milligrams (mg) once daily and pirfenidone up to 2403 mg daily orally for 24 weeks.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
January 5, 2016
Last Updated
October 26, 2017
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02648048
Brief Title
A Study of Oral Vismodegib in Combination With Pirfenidone in Participants With Idiopathic Pulmonary Fibrosis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
January 15, 2016 (Actual)
Primary Completion Date
November 30, 2016 (Actual)
Study Completion Date
November 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis
Keywords
Idiopathic Pulmonary Fibrosis, Vismodegib, Pirfenidone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vismodegib and Pirfenidone
Arm Type
Experimental
Arm Description
Participants being treated with pirfenidone, will receive vismodegib 150 milligrams (mg) once daily and pirfenidone up to 2403 mg daily orally for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Pirfenidone
Other Intervention Name(s)
RO0220912
Intervention Description
Pirfenidone will be administered as per the dosage schedule mentioned in arm description.
Intervention Type
Drug
Intervention Name(s)
Vismodegib
Other Intervention Name(s)
RO5450815
Intervention Description
Vismodegib will be administered as per the dosage schedule mentioned in arm description.
Primary Outcome Measure Information:
Title
Percentage of Participants with Serious and Non-Serious Adverse Events
Description
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.
Time Frame
Baseline up to 28 weeks
Title
Percentage of Participants with Discontinuation of Any Study Medication Due to a Drug-Related Adverse Event
Description
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.
Time Frame
Baseline up to 28 weeks
Title
Percentage of Participants with Dose Modifications Due to Laboratory Abnormalities and Adverse Events
Description
An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possibility of causal relationship.
Time Frame
Baseline up to 28 weeks
Title
Percentage of Participants with Clinically Meaningful Laboratory Abnormalities as Assessed by Investigator
Description
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.
Time Frame
Baseline up to 28 weeks
Secondary Outcome Measure Information:
Title
Total and Free Trough Plasma Concentrations of Vismodegib at Week 4 (Cmin, Wk4)
Description
Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + alpha-1-acid glycoprotein (AAG)-bound vismodegib plasma concentration.
Time Frame
Predose (0 hour) at Week 4
Title
Total and Free Trough Plasma Concentrations of Vismodegib at Week 12 (Cmin, Wk12)
Description
Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + AAG-bound vismodegib plasma concentration.
Time Frame
Predose (0 hour) at Week 12
Title
Total and Free Trough Plasma Concentrations of Vismodegib at Week 24 (Cmin, Wk24)
Description
Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + AAG-bound vismodegib plasma concentration.
Time Frame
Predose (0 hour) at Week 24
Title
Total and Free Trough Plasma Concentrations of Vismodegib at Safety Follow-up Visit (Cmin, SFU)
Description
Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + AAG-bound vismodegib plasma concentration.
Time Frame
At Day 30 post last dose (last dose = 24 weeks) (up to 28 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Central Florida Pulmonary Group, PA
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Suburban Lung Associates
City
Elk Grove
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
Medical Consultants, PC ; Pulmonary
City
Muncie
State/Province
Indiana
ZIP/Postal Code
47303
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202-1798
Country
United States
Facility Name
Tulane University Medical School
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Steward St. Elizabeth's Medical Center ; Pulmonary, Critical Care and Sleep Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02135
Country
United States
Facility Name
Creighton University Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
Allied Clinical Research
City
Reno
State/Province
Nevada
ZIP/Postal Code
89503
Country
United States
Facility Name
Atlantic Respiratory Institute
City
Summit
State/Province
New Jersey
ZIP/Postal Code
07901
Country
United States
Facility Name
Pulmonix LLC
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27403
Country
United States
Facility Name
PMG Research of Wilmington
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Western Washington Medical Group
City
Everett
State/Province
Washington
ZIP/Postal Code
98208
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM
City
Hannover
ZIP/Postal Code
30625
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
32026407
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.
Results Reference
derived

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

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