A Study of Lebrikizumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Roche

Status and phase: Completed; Phase 2

Conditions: Idiopathic Pulmonary Fibrosis

Treatments: Drug: Pirfenidone; Drug: Lebrikizumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01872689

GB28547

2013-001163-24 (EudraCT Number)

Details and patient eligibility

About

This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of lebrikizumab as monotherapy in the absence of background IPF therapy and as combination therapy with pirfenidone background therapy in participants with IPF. Participants will be randomized to receive either lebrikizumab or placebo subcutaneously every 4 weeks.

Enrollment: 505 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a diagnosis of IPF within the previous 5 years from time of screening and confirmed at baseline
• FVC >/=40 percent (%) and </=100% of predicted at screening
• Stable baseline lung function as evidenced by a difference of less than (<) 10% in FVC (in liters) measurements between screening and Day 1, Visit 2 prior to randomization
• DLco >/=25% and </=90% of predicted at screening
• Ability to walk >/=100 meters unassisted in 6 minutes
• Cohort A: No background IPF therapy for >/=4 weeks allowed prior to randomization and throughout the placebo-controlled study period
• Cohort B: Tolerated dose of pirfenidone </=2403 milligrams once daily (mg/day) for >/=4 weeks required prior to randomization and throughout the placebo-controlled study period

Exclusion criteria

• History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
• Evidence of other known causes of interstitial lung disease
• Lung transplant expected within 12 months of screening
• Evidence of clinically significant lung disease other than IPF
• Post-bronchodilator forced expiratory volume in 1 second (FEV1)/FVC ratio <0.7 at screening
• Positive bronchodilator response, evidenced by an increase of >/=12% predicted and 200 milliliters increase in FEV1 or FVC
• Class IV New York Heart Association chronic heart failure or historical evidence of left ventricular ejection fraction <35%
• Hospitalization due to an exacerbation of IPF within 4 weeks prior to or during screening
• Known current malignancy or current evaluation for potential malignancy
• Listeria monocytogenes infection or active parasitic infection within 6 months prior to Day 1, Visit 2
• Active tuberculosis requiring treatment within 12 months of screening
• Known immunodeficiency, including but not limited to human immunodeficiency virus infection
• Past use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
• Evidence of acute or chronic hepatitis or known liver cirrhosis

Exclusions Criteria Limited to Cohort B:

• Known achalasia, esophageal stricture, or esophageal dysfunction sufficient to limit the ability to swallow oral medication
• Tobacco smoking or use of tobacco-related products within 3 months of screening or unwillingness to avoid smoking throughout the study period
• Known or suspected peptic ulcer
• Any condition that, as assessed by the investigator, might be significantly exacerbated by the known side effects associated with pirfenidone
• Creatinine clearance <40 milliliters/minute, calculated using the Cockcroft-Gault formula
• Use of following therapies within 4 weeks of randomization (Day 1, Visit 2) or during the study: Strong inhibitors of CYP1A2 (Cytochrome P450 Family 1 Subfamily A Member 2) (example: fluvoxamine or enoxacin); Moderate inducers of CYP1A2 (limited to tobacco smoking and tobacco-related products)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

505 participants in 4 patient groups, including a placebo group

Monotherapy (Cohort A): Placebo

Placebo Comparator group

Description:

Participants will receive monotherapy with placebo matched to lebrikizumab administered via subcutaneous (SC) injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants will be allowed to receive treatment with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to additional 52 weeks (that is, up to Week 104) in the open-label period.

Treatment:

Drug: Placebo

Drug: Lebrikizumab

Monotherapy (Cohort A): Lebrikizumab

Experimental group

Description:

Participants will receive monotherapy with lebrikizumab at a dose of 250 milligrams (mg) administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants will be allowed to receive treatment with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to additional 52 weeks (that is, up to Week 104) in the open-label period.

Treatment:

Drug: Lebrikizumab

Combination Therapy (Cohort B): Placebo + Pirfenidone

Placebo Comparator group

Description:

Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day \[9 capsules daily\] for a total of 2403 mg/day) or at maximum tolerated dose (MTD) administered orally along with placebo matched to lebrikizumab administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.

Treatment:

Drug: Placebo

Drug: Pirfenidone

Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone

Experimental group

Description:

Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day \[9 capsules daily\] for a total of 2403 mg/day) or at MTD administered orally along with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.

Treatment:

Drug: Lebrikizumab

Drug: Pirfenidone