A Study of Lebrikizumab in Participants With Idiopathic Pulmonary Fibrosis - Full Text View

Purpose

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 idiopathic pulmonary fibrosis (IPF) therapy or as combination therapy with pirfenidone background therapy in participants with idiopathic pulmonary fibrosis. Participants will be randomized to receive either lebrikizumab or placebo subcutaneously (SC) every 4 weeks.

Condition	Intervention	Phase
Idiopathic Pulmonary Fibrosis	Drug: Lebrikizumab Drug: Pirfenidone Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Investigator Primary Purpose: Treatment
Official Title:	A Phase II, Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Idiopathic Pulmonary Fibrosis

Resource links provided by NLM:

Genetics Home Reference related topics: idiopathic pulmonary fibrosis

MedlinePlus related topics: Pulmonary Fibrosis

Drug Information available for: Pirfenidone

Genetic and Rare Diseases Information Center resources: Idiopathic Pulmonary Fibrosis

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 [ Time Frame: Baseline, Week 52 ]

Secondary Outcome Measures:

Progression Free Survival (PFS), Defined as Time From Randomization to Death, Non-elective Hospitalization, or a Decrease From Baseline of Greater Than or Equal to (>/=) 10 Percent (%) in FVC, Whichever Occurs First [ Time Frame: Baseline up to 18 weeks after last dose (last dose = Week 104) ]
Annualized Rate of Change in FVC (in Liters) [ Time Frame: Baseline up to Week 52 ]
Time to First Decrease From Baseline of >/=10% in FVC [ Time Frame: Baseline up to 18 weeks after last dose (last dose = Week 104) ]
Time to First Decrease From Baseline of >/= 15% in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) [ Time Frame: Baseline up to 18 weeks after last dose (last dose = Week 104) ]
Change From Baseline in the A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Score at Week 52 [ Time Frame: Baseline, Week 52 ]
Time to Non-elective Hospitalization From any Cause [ Time Frame: Baseline up to 18 weeks after last dose (last dose = Week 104) ]
Change From Baseline in 6-Minute Walk Test (6MWT) Distance at Week 52 [ Time Frame: Baseline, Week 52 ]
Time to First Event of Acute IPF Exacerbation [ Time Frame: Baseline up to 18 weeks after last dose (last dose = Week 104) ]
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Score at Week 52 [ Time Frame: Baseline, Week 52 ]
Percentage of Participants with Adverse Events or Serious Adverse Events [ Time Frame: Baseline up to 18 weeks after last dose (last dose = Week 104) ]
Percentage of Participants with Anti-therapeutic Antibody (ATA) to Lebrikizumab [ Time Frame: Baseline up to 18 weeks after last dose (last dose = Week 104) ]
Serum Lebrikizumab Concentration at Week 52 (Cwk52) [ Time Frame: Pre-dose (at Hour 0) at Week 52 ]
Minimum Observed Serum Trough Lebrikizumab Concentration (Cmin) at Week 4, 12, 24, and 36 [ Time Frame: Pre-dose (at Hour 0) at Weeks 4, 12, 24, and 36 ]
Elimination Half-Life (t1/2) of Lebrikizumab [ Time Frame: Pre-dose (at Hour 0) at Weeks 1, 4, 12, 24, 36, 64, 76, 88, 104; at 4, 12, and 18 weeks post-last dose (last dose = Week 104) ]


Enrollment:	507
Actual Study Start Date:	October 31, 2013
Estimated Study Completion Date:	November 15, 2017
Estimated Primary Completion Date:	November 15, 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort A: Monotherapy Lebrikizumab Monotherapy of lebrikizumab 250 milligrams (mg) will be administered SC once every 4 week up to 52 weeks placebo-controlled treatment period and thereafter for additional 52 weeks (i.e., up to Week 104) in the open-label period.	Drug: Lebrikizumab Administered SC every 4 weeks
Placebo Comparator: Cohort A: Monotherapy Placebo Placebo matched to lebrikizumab will be administered SC once every 4 week up to 52 week placebo-controlled treatment period. Thereafter will be followed by lebrikizumab 250 mg administered SC every 4 week for additional for 52 weeks (i.e., up to Week 104) in the open-label period.	Drug: Lebrikizumab Administered SC every 4 weeks Drug: Placebo Administered SC every 4 weeks
Experimental: Cohort B: Combination Therapy (Lebrikizumab + Pirfenidone) Pirfenidone </=2403 mg once daily (maximum tolerated dose) will be administered in combination with lebrikizumab 250 mg SC once every 4 week up to 52 week placebo-controlled treatment period.	Drug: Lebrikizumab Administered SC every 4 weeks Drug: Pirfenidone Administered daily at the maximum tolerated dose
Placebo Comparator: Cohort B: Combination Therapy (Placebo + Pirfenidone) Pirfenidone </=2403 mg once daily (maximum tolerated dose) will be administered in combination with placebo matched to lebrikizumab SC once every 4 week up to 52 week placebo-controlled treatment period.	Drug: Pirfenidone Administered daily at the maximum tolerated dose Drug: Placebo Administered SC every 4 weeks

Eligibility


Ages Eligible for Study:	40 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Have a diagnosis of IPF within the previous 5 years from time of screening and confirmed at baseline
FVC >/=40 % and less than or equal to (</=) 100% predicted at screening
Stable baseline lung function as evidenced by a difference of less than (<) 10% in FVC (liters) measurements between screening and Day 1/Visit 2 prior to randomization
Diffusion capacity of the lung for carbon monoxide >/=25% and </=90% 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/QD) 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 (ILD)
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 (mL) 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 infections within 6 months prior to randomization
Active tuberculosis requiring treatment within 12 months of screening
Known immunodeficiency, including but not limited to human immunodeficiency virus (HIV) infection
Past use of any anti-interleukin (IL)-13 or anti-IL-14/IL-13 therapy, including lebrikizumab
Evidence of acute or chronic hepatitis or known liver cirrhosis

Exclusions 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 mL/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)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01872689

Show 112 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01872689 History of Changes
Other Study ID Numbers:	GB28547 2013-001163-24 ( EudraCT Number )
Study First Received:	June 5, 2013
Last Updated:	May 18, 2017

Additional relevant MeSH terms:


Fibrosis Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Idiopathic Interstitial Pneumonias Pathologic Processes Lung Diseases Respiratory Tract Diseases Lung Diseases, Interstitial Pirfenidone Antibodies, Monoclonal	Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Anti-Inflammatory Agents Antirheumatic Agents Antineoplastic Agents Immunologic Factors

ClinicalTrials.gov processed this record on July 13, 2017