Idiopathic Pulmonary Fibrosis
Conditions
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.
Interventions
DRUGLebrikizumab
Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.
DRUGPirfenidone
Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.
DRUGPlacebo
Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks | Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52) | Annualized rates of decrease (slope throughout time from baseline to Week 52) for percent predicted FVC was assessed and reported. FVC is a standard pulmonary function test. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | 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) | FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100. |
| Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | 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) | FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100. Time from randomization to first occurrence of an event of \>/=10% absolute decline in percent predicted FVC or death from any cause was reported. Participants without an event were censored at the last assessment during the double-blind treatment period. Any participant who underwent lung transplantation was censored at the date of the transplant. The median time to event was estimated using Kaplan-Meier method. 95% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. |
| Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks | Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52) | Annualized rates of decrease (slope throughout time from baseline to Week 52) in DLco was assessed and reported. DLco (in milliliters per minute/millimeters of mercury \[mL/min/mmHg\]) is a measure of the gas transfer. |
| Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC | 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) | FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC = \[(observed FVC)/(predicted FVC)\]\*100. |
| Progression-Free Survival (PFS) | 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) | FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC = \[(observed FVC)/(predicted FVC)\]\*100. PFS was defined as time from randomization to death from any cause, all cause hospitalization, or a decrease from baseline of \>/=10% in FVC, whichever occurred first. Participants without an event were censored at the last assessment during the double-blind treatment period. Any participant who underwent lung transplantation was censored at the date of the transplant. The median PFS was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Annualized Rate of Decrease in FVC Over 52 Weeks | Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52) | Annualized rates of decrease (slope throughout time from baseline to Week 52) in FVC (in milliliters per year \[mL/year\]) was assessed and reported. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position. |
| Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks | Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52) | The ATAQ-IPF Version 3 was utilized that included 31 items within 5 domains: cough (6 items), dyspnea (7 items), exhaustion (6 items), emotional well-being (6 items), and independence (6 items). Each item was assessed on a scale ranging from 1 (Strongly disagree) to 4 (Strongly agree). The ATAQ-IPF had a recall specification of 2 weeks. Simple summation scoring was used to derive individual domain scores as well as a total score. ATAQ-IPF total score ranged from 31 to 124 with lower score indicating better quality of life (QoL). Annualized rates of decrease (slope throughout time from baseline to Week 52) in ATAQ-IPF questionnaire total score was assessed and reported. |
| Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause | Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122) | The SGRQ is a 50-item health-related QoL instrument that measured health impairment. The questionnaire contains 3 domains: symptoms, activity, and impacts. Items were assessed on various response scales, including a 5-point Likert scale and True/False scale. The SGRQ had a recall specification of 4 weeks. The SGRQ total score (summed weights) ranged from 0 to 100 with a lower score denoting a better health status. Percentage of participants with an event of SGRQ total score worsening (defined as reaching minimal important difference \[MID\], that is, an increase in total score of \>/=7) or death from any cause was reported. |
| Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause | Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122) | The SGRQ is a 50-item health-related QoL instrument that measured health impairment. The questionnaire contains 3 domains: symptoms, activity, and impacts. Items were assessed on various response scales, including a 5-point Likert scale and True/False scale. The SGRQ had a recall specification of 4 weeks. The SGRQ total score (summed weights) ranged from 0 to 100 with a lower score denoting a better health status. Time from randomization to first occurrence of an event of SGRQ total score worsening (defined as reaching minimal important difference \[MID\], that is, an increase in total score of \>/=7) or death from any cause was reported. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks | Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52) | Annualized rates of decline (slope throughout time from baseline to Week 52) in 6MWT was assessed and reported. 6MWT was the distance (in meters \[m\]) that a participant could walk in 6 minutes. |
| Time to First Event of Acute IPF Exacerbation | Baseline up to the event of acute IPF exacerbation (up to Week 122) | Time from randomization to first occurrence of an event of IPF exacerbation was reported. IPF exacerbation was defined as an event that met all of the following criteria as determined by the investigator: Unexplained worsening or development of dyspnea within the previous 30 days; And radiologic evidence of new bilateral ground-glass abnormality or consolidation, superimposed on a reticular or honeycomb background pattern, that is consistent with usual interstitial pneumonitis; And absence of alternative causes, or other events leading to acute lung injury. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Percentage of Participants With Respiratory-Related Hospitalization | Baseline up to the event of respiratory-related hospitalization (up to Week 122) | — |
| Time to Respiratory-Related Hospitalization | Baseline up to the event of respiratory-related hospitalization (up to Week 122) | Time from randomization to first occurrence of an event of respiratory-related hospitalization was reported. Participants without an event were censored at the last known alive day, study Day 368, or the last date during the double-blind period. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122) | DLco (in mL/min/mmHg) is a measure of the gas transfer. Predicted DLco is based on sex, age, and height of a person. Percent of predicted DLco (in %) = \[(observed DLco)/(predicted DLco)\]\*100. |
| Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122) | DLco is a measure of the gas transfer. Predicted DLco is based on sex, age, and height of a person. Percent of predicted DLco (in %) = \[(observed DLco)/(predicted DLco)\]\*100. Time from randomization to first occurrence of \>/=15% absolute decrease in percentage of predicted DLco or death from any cause was reported. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab | 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) | ATA to lebrikizumab was tested using a validated immunoassay. A positive ATA result was defined as one in which the presence of detectable ATAs could be confirmed by competitive binding with lebrikizumab. Percentage of participants with positive results for ATA at Baseline and at post-baseline time points were reported. Only participants who received lebrikizumab were included in the analysis. |
| Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52 | Predose (Hour 0) at Week 52 | Participants who received lebrikizumab were only included in the analysis. |
| Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Predose (Hour 0) at Weeks 4, 12, 24, and 36 | Participants who received lebrikizumab were only included in the analysis. |
| Elimination Half-Life (t1/2) of Lebrikizumab | 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) | Elimination half-life is the time measured for the plasma drug concentration to decrease by one-half during the elimination phase of the drug. Analysis was performed on PK-Evaluable Population. Participants who received lebrikizumab were only included in the analysis. |
| Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | Baseline up to the event of acute IPF exacerbation (up to Week 122) | IPF exacerbation was defined as an event that met all of the following criteria as determined by the investigator: Unexplained worsening or development of dyspnea within the previous 30 days; And radiologic evidence of new bilateral ground-glass abnormality or consolidation, superimposed on a reticular or honeycomb background pattern, that is consistent with usual interstitial pneumonitis; And absence of alternative causes, such as left heart failure, pulmonary embolism, pulmonary infection (on the basis of endotracheal aspirate or bronchoalveolar lavage if available, or investigator judgment), or other events leading to acute lung injury (for example, sepsis, aspiration, trauma, reperfusion pulmonary edema). |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Japan, Mexico, Peru, Poland, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 505 participants (154 participants in Monotherapy Cohort and 351 participants in Combination Therapy Cohort) were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy (Cohort A): Placebo Participants received monotherapy with placebo matched to lebrikizumab administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants were 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. | 76 |
| Monotherapy (Cohort A): Lebrikizumab Participants received monotherapy 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. Participants were 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. | 78 |
| Combination Therapy (Cohort B): Placebo + Pirfenidone Participants received 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 placebo matched to lebrikizumab administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. | 177 |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone Participants received 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. | 174 |
| Total | 505 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind/Placebo-Controlled Period | Adverse Event | 6 | 3 | 10 | 7 |
| Double-Blind/Placebo-Controlled Period | Death | 3 | 4 | 14 | 9 |
| Double-Blind/Placebo-Controlled Period | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Double-Blind/Placebo-Controlled Period | Lost to Follow-up | 1 | 0 | 0 | 1 |
| Double-Blind/Placebo-Controlled Period | Other | 1 | 1 | 6 | 3 |
| Double-Blind/Placebo-Controlled Period | Physician Decision | 0 | 3 | 3 | 1 |
| Double-Blind/Placebo-Controlled Period | Protocol Violation | 0 | 0 | 1 | 1 |
| Double-Blind/Placebo-Controlled Period | Withdrawal by Subject | 9 | 8 | 14 | 16 |
| Open-Label Period (Only For Monotherapy) | Adverse Event | 2 | 1 | 0 | 0 |
| Open-Label Period (Only For Monotherapy) | Death | 5 | 3 | 0 | 0 |
| Open-Label Period (Only For Monotherapy) | Lost to Follow-up | 1 | 3 | 0 | 0 |
| Open-Label Period (Only For Monotherapy) | Other | 2 | 3 | 0 | 0 |
| Open-Label Period (Only For Monotherapy) | Physician Decision | 0 | 1 | 0 | 0 |
| Open-Label Period (Only For Monotherapy) | Withdrawal by Subject | 11 | 12 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Combination Therapy (Cohort B): Placebo + Pirfenidone | Monotherapy (Cohort A): Lebrikizumab | Monotherapy (Cohort A): Placebo |
|---|---|---|---|---|---|
| Age, Customized >/=75 years | 112 participants | 39 participants | 32 participants | 23 participants | 18 participants |
| Age, Customized From 40 to <55 years | 11 participants | 2 participants | 6 participants | 1 participants | 2 participants |
| Age, Customized From 55 to <65 years | 109 participants | 41 participants | 40 participants | 10 participants | 18 participants |
| Age, Customized From 65 to <75 years | 273 participants | 92 participants | 99 participants | 44 participants | 38 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants | 15 Participants | 13 Participants | 6 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 447 Participants | 155 Participants | 160 Participants | 68 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 53 Participants | 15 Participants | 19 Participants | 8 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 6 Participants | 7 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 426 Participants | 151 Participants | 149 Participants | 66 Participants | 60 Participants |
| Sex: Female, Male Female | 93 Participants | 37 Participants | 30 Participants | 13 Participants | 13 Participants |
| Sex: Female, Male Male | 412 Participants | 137 Participants | 147 Participants | 65 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 76 | 4 / 78 | 15 / 177 | 7 / 174 |
| other Total, other adverse events | 70 / 76 | 73 / 78 | 158 / 177 | 142 / 174 |
| serious Total, serious adverse events | 19 / 76 | 23 / 78 | 47 / 177 | 56 / 174 |
Outcome results
Primary
Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks
Annualized rates of decrease (slope throughout time from baseline to Week 52) for percent predicted FVC was assessed and reported. FVC is a standard pulmonary function test. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100.
Time frame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure at Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks | -6.1876 percent predicted FVC/year | Standard Error 0.92597 |
| Monotherapy (Cohort A): Lebrikizumab | Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks | -5.2065 percent predicted FVC/year | Standard Error 0.92758 |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks | -6.0430 percent predicted FVC/year | Standard Error 0.60633 |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks | -5.5430 percent predicted FVC/year | Standard Error 0.59507 |
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.455595% CI: [-1.61, 3.57]Mixed Models Analysis
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.556695% CI: [-1.17, 2.17]Mixed Models Analysis
Secondary
Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks
Annualized rates of decline (slope throughout time from baseline to Week 52) in 6MWT was assessed and reported. 6MWT was the distance (in meters \[m\]) that a participant could walk in 6 minutes.
Time frame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure at Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks | -44.6512 m/year | Standard Error 15.97862 |
| Monotherapy (Cohort A): Lebrikizumab | Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks | -22.7209 m/year | Standard Error 15.34753 |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks | -25.5683 m/year | Standard Error 12.24923 |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks | -46.9810 m/year | Standard Error 11.84199 |
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.312995% CI: [-20.97, 64.83]Mixed Models Analysis
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.203695% CI: [-54.5, 11.67]Mixed Models Analysis
Secondary
Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks
The ATAQ-IPF Version 3 was utilized that included 31 items within 5 domains: cough (6 items), dyspnea (7 items), exhaustion (6 items), emotional well-being (6 items), and independence (6 items). Each item was assessed on a scale ranging from 1 (Strongly disagree) to 4 (Strongly agree). The ATAQ-IPF had a recall specification of 2 weeks. Simple summation scoring was used to derive individual domain scores as well as a total score. ATAQ-IPF total score ranged from 31 to 124 with lower score indicating better quality of life (QoL). Annualized rates of decrease (slope throughout time from baseline to Week 52) in ATAQ-IPF questionnaire total score was assessed and reported.
Time frame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure at Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks | 6.8907 units on a scale/year | Standard Error 1.71778 |
| Monotherapy (Cohort A): Lebrikizumab | Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks | 4.7886 units on a scale/year | Standard Error 1.7037 |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks | 5.6189 units on a scale/year | Standard Error 0.9988 |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks | 5.4558 units on a scale/year | Standard Error 0.97793 |
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.385495% CI: [-6.88, 2.68]Mixed Models Analysis
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.905795% CI: [-2.87, 2.55]Mixed Models Analysis
Secondary
Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks
Annualized rates of decrease (slope throughout time from baseline to Week 52) in DLco was assessed and reported. DLco (in milliliters per minute/millimeters of mercury \[mL/min/mmHg\]) is a measure of the gas transfer.
Time frame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure at Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks | -4.7818 mL/min/mmHg/year | Standard Error 0.74479 |
| Monotherapy (Cohort A): Lebrikizumab | Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks | -4.2400 mL/min/mmHg/year | Standard Error 0.73826 |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks | -5.7552 mL/min/mmHg/year | Standard Error 0.46561 |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks | -5.5732 mL/min/mmHg/year | Standard Error 0.45577 |
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.607595% CI: [-1.54, 2.62]Mixed Models Analysis
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.780395% CI: [-1.1, 1.47]Mixed Models Analysis
Secondary
Annualized Rate of Decrease in FVC Over 52 Weeks
Annualized rates of decrease (slope throughout time from baseline to Week 52) in FVC (in milliliters per year \[mL/year\]) was assessed and reported. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position.
Time frame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure at Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Annualized Rate of Decrease in FVC Over 52 Weeks | -221.029 mL/year | Standard Error 34.87511 |
| Monotherapy (Cohort A): Lebrikizumab | Annualized Rate of Decrease in FVC Over 52 Weeks | -192.906 mL/year | Standard Error 34.93853 |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Annualized Rate of Decrease in FVC Over 52 Weeks | -231.167 mL/year | Standard Error 22.67786 |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Annualized Rate of Decrease in FVC Over 52 Weeks | -209.437 mL/year | Standard Error 22.25073 |
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.570795% CI: [-69.8, 126.04]Mixed Models Analysis
Comparison: Mixed Linear model comparing Lebrikizumab to Placebo, with assessment as the outcome variable; assessment time by treatment as fixed effects; and participant baseline FVC (\<50%, 50 to 75%, \>75%) and participant by assessment time as random effects with unstructured covariance.p-value: 0.493495% CI: [-40.65, 84.11]Mixed Models Analysis
Secondary
Elimination Half-Life (t1/2) of Lebrikizumab
Elimination half-life is the time measured for the plasma drug concentration to decrease by one-half during the elimination phase of the drug. Analysis was performed on PK-Evaluable Population. Participants who received lebrikizumab were only included in the analysis.
Time frame: 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)
Population: Analysis was performed on PK-Evaluable Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Elimination Half-Life (t1/2) of Lebrikizumab | 23.5 days | Standard Deviation 5.36 |
| Monotherapy (Cohort A): Lebrikizumab | Elimination Half-Life (t1/2) of Lebrikizumab | 21.9 days | Standard Deviation 4.79 |
Secondary
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab
Participants who received lebrikizumab were only included in the analysis.
Time frame: Predose (Hour 0) at Weeks 4, 12, 24, and 36
Population: Analysis was performed on PK-Evaluable Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 4 | 14.0 mcg/mL | Standard Deviation 4.86 |
| Monotherapy (Cohort A): Placebo | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 12 | 24.4 mcg/mL | Standard Deviation 9.86 |
| Monotherapy (Cohort A): Placebo | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 24 | 28.5 mcg/mL | Standard Deviation 12.5 |
| Monotherapy (Cohort A): Placebo | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 36 | 29.9 mcg/mL | Standard Deviation 14.1 |
| Monotherapy (Cohort A): Lebrikizumab | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 36 | 25.6 mcg/mL | Standard Deviation 13.8 |
| Monotherapy (Cohort A): Lebrikizumab | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 4 | 14.9 mcg/mL | Standard Deviation 5.75 |
| Monotherapy (Cohort A): Lebrikizumab | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 24 | 25.7 mcg/mL | Standard Deviation 12.4 |
| Monotherapy (Cohort A): Lebrikizumab | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab | Cmin at Week 12 | 25.0 mcg/mL | Standard Deviation 11 |
Secondary
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52
Participants who received lebrikizumab were only included in the analysis.
Time frame: Predose (Hour 0) at Week 52
Population: Analysis was performed on Pharmacokinetic (PK)-Evaluable Population, which included all participants who received at least one dose of study drug and had at least one non-missing PK observation. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure at Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52 | 29.6 micrograms per milliliter (mcg/mL) | Standard Deviation 14 |
| Monotherapy (Cohort A): Lebrikizumab | Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52 | 25.2 micrograms per milliliter (mcg/mL) | Standard Deviation 12.7 |
Secondary
Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
DLco (in mL/min/mmHg) is a measure of the gas transfer. Predicted DLco is based on sex, age, and height of a person. Percent of predicted DLco (in %) = \[(observed DLco)/(predicted DLco)\]\*100.
Time frame: Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | 9.2 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | 6.6 percentage of participants |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | 14.9 percentage of participants |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | 11.0 percentage of participants |
Secondary
Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
IPF exacerbation was defined as an event that met all of the following criteria as determined by the investigator: Unexplained worsening or development of dyspnea within the previous 30 days; And radiologic evidence of new bilateral ground-glass abnormality or consolidation, superimposed on a reticular or honeycomb background pattern, that is consistent with usual interstitial pneumonitis; And absence of alternative causes, such as left heart failure, pulmonary embolism, pulmonary infection (on the basis of endotracheal aspirate or bronchoalveolar lavage if available, or investigator judgment), or other events leading to acute lung injury (for example, sepsis, aspiration, trauma, reperfusion pulmonary edema).
Time frame: Baseline up to the event of acute IPF exacerbation (up to Week 122)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | 3.9 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | 3.9 percentage of participants |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | 6.3 percentage of participants |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | 2.9 percentage of participants |
Secondary
Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause
The SGRQ is a 50-item health-related QoL instrument that measured health impairment. The questionnaire contains 3 domains: symptoms, activity, and impacts. Items were assessed on various response scales, including a 5-point Likert scale and True/False scale. The SGRQ had a recall specification of 4 weeks. The SGRQ total score (summed weights) ranged from 0 to 100 with a lower score denoting a better health status. Percentage of participants with an event of SGRQ total score worsening (defined as reaching minimal important difference \[MID\], that is, an increase in total score of \>/=7) or death from any cause was reported.
Time frame: Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
Population: Analysis was performed on ITT Population for monotherapy cohort only. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause | 57.9 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause | 48.7 percentage of participants |
Secondary
Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab
ATA to lebrikizumab was tested using a validated immunoassay. A positive ATA result was defined as one in which the presence of detectable ATAs could be confirmed by competitive binding with lebrikizumab. Percentage of participants with positive results for ATA at Baseline and at post-baseline time points were reported. Only participants who received lebrikizumab were included in the analysis.
Time frame: 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)
Population: Analysis was performed on Safety Population (all participants who received at least one dose of study drug grouped according to the actual treatment received). 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at indicated time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy (Cohort A): Placebo | Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab | Baseline | 5.3 percentage of participants |
| Monotherapy (Cohort A): Placebo | Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab | Post-Baseline | 6.7 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab | Baseline | 1.8 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab | Post-Baseline | 5.2 percentage of participants |
Secondary
Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC
FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC = \[(observed FVC)/(predicted FVC)\]\*100.
Time frame: 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)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC | 47.4 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC | 32.9 percentage of participants |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC | 39.4 percentage of participants |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC | 39.9 percentage of participants |
Secondary
Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100.
Time frame: 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)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | 34.2 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | 27.6 percentage of participants |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | 30.3 percentage of participants |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | 26.6 percentage of participants |
Secondary
Percentage of Participants With Respiratory-Related Hospitalization
Time frame: Baseline up to the event of respiratory-related hospitalization (up to Week 122)
Population: Analysis was performed on ITT Population for combination therapy cohorts only. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Percentage of Participants With Respiratory-Related Hospitalization | 15.4 percentage of participants |
| Monotherapy (Cohort A): Lebrikizumab | Percentage of Participants With Respiratory-Related Hospitalization | 14.5 percentage of participants |
Secondary
Progression-Free Survival (PFS)
FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC = \[(observed FVC)/(predicted FVC)\]\*100. PFS was defined as time from randomization to death from any cause, all cause hospitalization, or a decrease from baseline of \>/=10% in FVC, whichever occurred first. Participants without an event were censored at the last assessment during the double-blind treatment period. Any participant who underwent lung transplantation was censored at the date of the transplant. The median PFS was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time frame: 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)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Progression-Free Survival (PFS) | 52.6 weeks |
| Monotherapy (Cohort A): Lebrikizumab | Progression-Free Survival (PFS) | NA weeks |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Progression-Free Survival (PFS) | NA weeks |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Progression-Free Survival (PFS) | NA weeks |
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.097295% CI: [0.39, 1.09]Log Rank
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.934495% CI: [0.72, 1.42]Log Rank
Secondary
Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
DLco is a measure of the gas transfer. Predicted DLco is based on sex, age, and height of a person. Percent of predicted DLco (in %) = \[(observed DLco)/(predicted DLco)\]\*100. Time from randomization to first occurrence of \>/=15% absolute decrease in percentage of predicted DLco or death from any cause was reported. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time frame: Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | NA weeks |
| Monotherapy (Cohort A): Lebrikizumab | Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | NA weeks |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | NA weeks |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause | NA weeks |
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.568595% CI: [0.23, 2.26]Log Rank
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.197695% CI: [0.37, 1.23]Log Rank
Secondary
Time to First Event of Acute IPF Exacerbation
Time from randomization to first occurrence of an event of IPF exacerbation was reported. IPF exacerbation was defined as an event that met all of the following criteria as determined by the investigator: Unexplained worsening or development of dyspnea within the previous 30 days; And radiologic evidence of new bilateral ground-glass abnormality or consolidation, superimposed on a reticular or honeycomb background pattern, that is consistent with usual interstitial pneumonitis; And absence of alternative causes, or other events leading to acute lung injury. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time frame: Baseline up to the event of acute IPF exacerbation (up to Week 122)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Time to First Event of Acute IPF Exacerbation | NA weeks |
| Monotherapy (Cohort A): Lebrikizumab | Time to First Event of Acute IPF Exacerbation | NA weeks |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Time to First Event of Acute IPF Exacerbation | NA weeks |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Time to First Event of Acute IPF Exacerbation | NA weeks |
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.936695% CI: [0.21, 5.3]Log Rank
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.134695% CI: [0.16, 1.31]Log Rank
Secondary
Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100. Time from randomization to first occurrence of an event of \>/=10% absolute decline in percent predicted FVC or death from any cause was reported. Participants without an event were censored at the last assessment during the double-blind treatment period. Any participant who underwent lung transplantation was censored at the date of the transplant. The median time to event was estimated using Kaplan-Meier method. 95% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.
Time frame: 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)
Population: Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | 53.1 weeks |
| Monotherapy (Cohort A): Lebrikizumab | Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | NA weeks |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | NA weeks |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause | NA weeks |
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.429995% CI: [0.44, 1.41]Log Rank
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.375195% CI: [0.56, 1.24]Log Rank
Secondary
Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause
The SGRQ is a 50-item health-related QoL instrument that measured health impairment. The questionnaire contains 3 domains: symptoms, activity, and impacts. Items were assessed on various response scales, including a 5-point Likert scale and True/False scale. The SGRQ had a recall specification of 4 weeks. The SGRQ total score (summed weights) ranged from 0 to 100 with a lower score denoting a better health status. Time from randomization to first occurrence of an event of SGRQ total score worsening (defined as reaching minimal important difference \[MID\], that is, an increase in total score of \>/=7) or death from any cause was reported. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time frame: Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
Population: Analysis was performed on ITT Population for monotherapy cohort only. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause | 51.7 weeks |
| Monotherapy (Cohort A): Lebrikizumab | Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause | 52.3 weeks |
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.443395% CI: [0.54, 1.31]Log Rank
Secondary
Time to Respiratory-Related Hospitalization
Time from randomization to first occurrence of an event of respiratory-related hospitalization was reported. Participants without an event were censored at the last known alive day, study Day 368, or the last date during the double-blind period. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time frame: Baseline up to the event of respiratory-related hospitalization (up to Week 122)
Population: Analysis was performed on ITT Population for combination therapy cohorts only. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Time to Respiratory-Related Hospitalization | NA weeks |
| Monotherapy (Cohort A): Lebrikizumab | Time to Respiratory-Related Hospitalization | NA weeks |
Comparison: Stratified Analysis: stratified by baseline FVC (\<50%, 50 to 75%, \>75%)p-value: 0.681595% CI: [0.52, 1.54]Log Rank