Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Idiopathic Pulmonary Fibrosis, Vismodegib, Pirfenidone
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.
Interventions
DRUGPirfenidone
Pirfenidone will be administered as per the dosage schedule mentioned in arm description.
DRUGVismodegib
Vismodegib will be administered as per the dosage schedule mentioned in arm description.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Clinically Meaningful Laboratory Abnormalities as Assessed by Investigator | Baseline up to 28 weeks | 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. |
| Percentage of Participants with Serious and Non-Serious Adverse Events | Baseline up to 28 weeks | 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 | Baseline up to 28 weeks | 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 | Baseline up to 28 weeks | An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possibility of causal relationship. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total and Free Trough Plasma Concentrations of Vismodegib at Week 4 (Cmin, Wk4) | Predose (0 hour) at Week 4 | 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) | Predose (0 hour) at Week 12 | 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) | Predose (0 hour) at Week 24 | 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) | At Day 30 post last dose (last dose = 24 weeks) (up to 28 weeks) | Total plasma concentration of vismodegib = free (unbound) vismodegib plasma concentration + AAG-bound vismodegib plasma concentration. |
Countries
Germany, United States
Outcome results
None listed