Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01872689




Registration number
NCT01872689
Ethics application status
Date submitted
5/06/2013
Date registered
7/06/2013
Date last updated
24/08/2018

Titles & IDs
Public title
A Study of Lebrikizumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
Scientific title
A Phase II, Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Idiopathic Pulmonary Fibrosis
Secondary ID [1] 0 0
2013-001163-24
Secondary ID [2] 0 0
GB28547
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lebrikizumab
Treatment: Drugs - Pirfenidone
Treatment: Drugs - Placebo

Placebo comparator: Monotherapy (Cohort A): Placebo - 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.

Experimental: Monotherapy (Cohort A): Lebrikizumab - 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.

Placebo comparator: Combination Therapy (Cohort B): Placebo + Pirfenidone - 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.

Experimental: Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone - 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: Drugs: Lebrikizumab
Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.

Treatment: Drugs: Pirfenidone
Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.

Treatment: Drugs: Placebo
Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks
Timepoint [1] 0 0
Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Secondary outcome [1] 0 0
Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks
Timepoint [1] 0 0
Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Secondary outcome [2] 0 0
Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
Timepoint [2] 0 0
Baseline up to the event of >/=10% absolute decline in percent predicted FVC or death from any cause, whichever occurred first (up to Week 122)
Secondary outcome [3] 0 0
Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
Timepoint [3] 0 0
Baseline up to the event of >/=10% absolute decline in percent predicted FVC or death from any cause, whichever occurred first (up to Week 122)
Secondary outcome [4] 0 0
Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks
Timepoint [4] 0 0
Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Secondary outcome [5] 0 0
Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC
Timepoint [5] 0 0
Baseline up to the event of death from any cause, all cause hospitalization, or a decrease from baseline of >/=10% in FVC, whichever occurred first (up to Week 122)
Secondary outcome [6] 0 0
Progression-Free Survival (PFS)
Timepoint [6] 0 0
Baseline up to the event of death from any cause, all cause hospitalization, or a decrease from baseline of >/=10% in FVC, whichever occurred first (up to Week 122)
Secondary outcome [7] 0 0
Annualized Rate of Decrease in FVC Over 52 Weeks
Timepoint [7] 0 0
Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Secondary outcome [8] 0 0
Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks
Timepoint [8] 0 0
Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Secondary outcome [9] 0 0
Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause
Timepoint [9] 0 0
Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
Secondary outcome [10] 0 0
Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause
Timepoint [10] 0 0
Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
Secondary outcome [11] 0 0
Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
Timepoint [11] 0 0
Baseline up to the event of acute IPF exacerbation (up to Week 122)
Secondary outcome [12] 0 0
Time to First Event of Acute IPF Exacerbation
Timepoint [12] 0 0
Baseline up to the event of acute IPF exacerbation (up to Week 122)
Secondary outcome [13] 0 0
Percentage of Participants With Respiratory-Related Hospitalization
Timepoint [13] 0 0
Baseline up to the event of respiratory-related hospitalization (up to Week 122)
Secondary outcome [14] 0 0
Time to Respiratory-Related Hospitalization
Timepoint [14] 0 0
Baseline up to the event of respiratory-related hospitalization (up to Week 122)
Secondary outcome [15] 0 0
Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
Timepoint [15] 0 0
Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
Secondary outcome [16] 0 0
Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
Timepoint [16] 0 0
Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
Secondary outcome [17] 0 0
Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab
Timepoint [17] 0 0
Baseline and Post-Baseline (assessed at multiple time points: Weeks 4, 12, 24, 36, 52, 56, 64, 76, and at safety follow-up up to Week 122)
Secondary outcome [18] 0 0
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52
Timepoint [18] 0 0
Predose (Hour 0) at Week 52
Secondary outcome [19] 0 0
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab
Timepoint [19] 0 0
Predose (Hour 0) at Weeks 4, 12, 24, and 36
Secondary outcome [20] 0 0
Elimination Half-Life (t1/2) of Lebrikizumab
Timepoint [20] 0 0
Pre-dose (Hour 0) at Weeks 1, 4, 12, 24, 36, 64, 76, 88, 104; and at 4, 12, and 18 weeks post-last dose (last dose = Week 104)

Eligibility
Key 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
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/11/2017
Sample size
Target
Accrual to date
Final
505
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital; Department of Respiratory Medicine - Camperdown
Recruitment hospital [2] 0 0
ST VINCENT'S HOSPITAL; Thoracic Medicine - Darlinghurst
Recruitment hospital [3] 0 0
Box Hill Hospital; Eastern Clinical Research Unit - Box Hill
Recruitment hospital [4] 0 0
Alfred Hospital; Allergy Immuno Resp - Melbourne
Recruitment hospital [5] 0 0
Institute for Respiratory Health Inc - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Maine
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Nebraska
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
Rhode Island
Country [24] 0 0
United States of America
State/province [24] 0 0
South Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
Tennessee
Country [26] 0 0
United States of America
State/province [26] 0 0
Texas
Country [27] 0 0
United States of America
State/province [27] 0 0
Utah
Country [28] 0 0
United States of America
State/province [28] 0 0
Vermont
Country [29] 0 0
United States of America
State/province [29] 0 0
Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
United States of America
State/province [31] 0 0
Wisconsin
Country [32] 0 0
Belgium
State/province [32] 0 0
Bruxelles
Country [33] 0 0
Belgium
State/province [33] 0 0
Leuven
Country [34] 0 0
Belgium
State/province [34] 0 0
Mont-godinne
Country [35] 0 0
Canada
State/province [35] 0 0
British Columbia
Country [36] 0 0
Canada
State/province [36] 0 0
New Brunswick
Country [37] 0 0
Canada
State/province [37] 0 0
Ontario
Country [38] 0 0
Canada
State/province [38] 0 0
Quebec
Country [39] 0 0
France
State/province [39] 0 0
Bobigny
Country [40] 0 0
France
State/province [40] 0 0
Bron
Country [41] 0 0
France
State/province [41] 0 0
Lille
Country [42] 0 0
France
State/province [42] 0 0
Paris
Country [43] 0 0
France
State/province [43] 0 0
Rennes
Country [44] 0 0
Germany
State/province [44] 0 0
Essen
Country [45] 0 0
Germany
State/province [45] 0 0
Gießen
Country [46] 0 0
Germany
State/province [46] 0 0
Großhansdorf
Country [47] 0 0
Germany
State/province [47] 0 0
Heidelberg
Country [48] 0 0
Germany
State/province [48] 0 0
Immenhausen
Country [49] 0 0
Germany
State/province [49] 0 0
München
Country [50] 0 0
Italy
State/province [50] 0 0
Emilia-Romagna
Country [51] 0 0
Italy
State/province [51] 0 0
Lazio
Country [52] 0 0
Italy
State/province [52] 0 0
Lombardia
Country [53] 0 0
Italy
State/province [53] 0 0
Piemonte
Country [54] 0 0
Italy
State/province [54] 0 0
Sicilia
Country [55] 0 0
Italy
State/province [55] 0 0
Toscana
Country [56] 0 0
Japan
State/province [56] 0 0
Kanagawa
Country [57] 0 0
Japan
State/province [57] 0 0
Osaka
Country [58] 0 0
Japan
State/province [58] 0 0
Seto-shi
Country [59] 0 0
Mexico
State/province [59] 0 0
Hermosillo
Country [60] 0 0
Mexico
State/province [60] 0 0
Mexico City
Country [61] 0 0
Mexico
State/province [61] 0 0
Monterrey
Country [62] 0 0
Peru
State/province [62] 0 0
Lima
Country [63] 0 0
Poland
State/province [63] 0 0
Lodz
Country [64] 0 0
Poland
State/province [64] 0 0
Lublin
Country [65] 0 0
Poland
State/province [65] 0 0
Poznan
Country [66] 0 0
Poland
State/province [66] 0 0
Warszawa
Country [67] 0 0
Poland
State/province [67] 0 0
Zabrze
Country [68] 0 0
Spain
State/province [68] 0 0
Barcelona
Country [69] 0 0
Spain
State/province [69] 0 0
Madrid
Country [70] 0 0
Spain
State/province [70] 0 0
Sevilla
Country [71] 0 0
Spain
State/province [71] 0 0
Valencia
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Bristol
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Cambridge
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Hampshire
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Leeds
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Liverpool
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01872689