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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
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United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
State/province [3] 0 0
California
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United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
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Connecticut
Country [6] 0 0
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Florida
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Georgia
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Illinois
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Iowa
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Kansas
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Maine
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Italy
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Sicilia
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Italy
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Toscana
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Kanagawa
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Osaka
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Seto-shi
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Hermosillo
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Mexico City
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Monterrey
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Peru
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Lima
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Lodz
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Lublin
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Poznan
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London
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Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01872689
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