Trial Outcomes & Findings for A Study of Lebrikizumab in Participants With Idiopathic Pulmonary Fibrosis (IPF) (NCT NCT01872689)

Last Updated: 2018-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

505 participants

Primary outcome timeframe

Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)

Results posted on

2018-08-24

Participant Flow

A total of 505 participants (154 participants in Monotherapy Cohort and 351 participants in Combination Therapy Cohort) were enrolled in the study.

Participant milestones

Participant milestones
Measure	Monotherapy (Cohort A): Placebo Participants received 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 were allowed to receive treatment with lebrikizumab at a dose of 250 milligrams (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.	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.	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 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.	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.
Double-Blind/Placebo-Controlled Period STARTED	76	78	177	174
Double-Blind/Placebo-Controlled Period COMPLETED	56	58	129	136
Double-Blind/Placebo-Controlled Period NOT COMPLETED	20	20	48	38
Open-Label Period (Only For Monotherapy) STARTED	52	56	0	0
Open-Label Period (Only For Monotherapy) COMPLETED	31	33	0	0
Open-Label Period (Only For Monotherapy) NOT COMPLETED	21	23	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Monotherapy (Cohort A): Placebo Participants received 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 were allowed to receive treatment with lebrikizumab at a dose of 250 milligrams (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.	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.	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 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.	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.
Double-Blind/Placebo-Controlled Period Lack of Efficacy	0	1	0	0
Double-Blind/Placebo-Controlled Period Other	1	1	6	3
Double-Blind/Placebo-Controlled Period Withdrawal by Subject	9	8	14	16
Double-Blind/Placebo-Controlled Period Protocol Violation	0	0	1	1
Double-Blind/Placebo-Controlled Period Physician Decision	0	3	3	1
Double-Blind/Placebo-Controlled Period Lost to Follow-up	1	0	0	1
Double-Blind/Placebo-Controlled Period Death	3	4	14	9
Double-Blind/Placebo-Controlled Period Adverse Event	6	3	10	7
Open-Label Period (Only For Monotherapy) Other	2	3	0	0
Open-Label Period (Only For Monotherapy) Withdrawal by Subject	11	12	0	0
Open-Label Period (Only For Monotherapy) Physician Decision	0	1	0	0
Open-Label Period (Only For Monotherapy) Lost to Follow-up	1	3	0	0
Open-Label Period (Only For Monotherapy) Death	5	3	0	0
Open-Label Period (Only For Monotherapy) Adverse Event	2	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=78 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=177 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=174 Participants 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.	Total n=505 Participants Total of all reporting groups
Age, Customized From 40 to <55 years	2 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants	2 participants n=4 Participants	11 participants n=21 Participants
Age, Customized From 55 to <65 years	18 participants n=5 Participants	10 participants n=7 Participants	40 participants n=5 Participants	41 participants n=4 Participants	109 participants n=21 Participants
Age, Customized From 65 to <75 years	38 participants n=5 Participants	44 participants n=7 Participants	99 participants n=5 Participants	92 participants n=4 Participants	273 participants n=21 Participants
Age, Customized >/=75 years	18 participants n=5 Participants	23 participants n=7 Participants	32 participants n=5 Participants	39 participants n=4 Participants	112 participants n=21 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants	37 Participants n=4 Participants	93 Participants n=21 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	65 Participants n=7 Participants	147 Participants n=5 Participants	137 Participants n=4 Participants	412 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants	15 Participants n=4 Participants	43 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=5 Participants	68 Participants n=7 Participants	160 Participants n=5 Participants	155 Participants n=4 Participants	447 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants	15 Participants n=4 Participants	53 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	66 Participants n=7 Participants	149 Participants n=5 Participants	151 Participants n=4 Participants	426 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	6 Participants n=4 Participants	18 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=53 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=56 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=120 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=134 Participants 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.
Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks	-6.1876 percent predicted FVC/year Standard Error 0.92597	-5.2065 percent predicted FVC/year Standard Error 0.92758	-6.0430 percent predicted FVC/year Standard Error 0.60633	-5.5430 percent predicted FVC/year Standard Error 0.59507

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=52 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=59 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=120 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=129 Participants 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.
Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks	-44.6512 m/year Standard Error 15.97862	-22.7209 m/year Standard Error 15.34753	-25.5683 m/year Standard Error 12.24923	-46.9810 m/year Standard Error 11.84199

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=173 Participants 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.
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	27.6 percentage of participants	30.3 percentage of participants	26.6 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=173 Participants 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.
Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause	53.1 weeks Interval 52.6 to Upper limit of 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Interval 52.9 to Median and upper limit of 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=50 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=52 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=112 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=122 Participants 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.
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	-4.2400 mL/min/mmHg/year Standard Error 0.73826	-5.7552 mL/min/mmHg/year Standard Error 0.46561	-5.5732 mL/min/mmHg/year Standard Error 0.45577

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=173 Participants 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.
Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC	47.4 percentage of participants	32.9 percentage of participants	39.4 percentage of participants	39.9 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=173 Participants 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.
Progression-Free Survival (PFS)	52.6 weeks Interval 43.9 to Upper limit of 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Interval 52.3 to Median and upper limit of 95% CI could not be estimated due to high number of censored participants.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=53 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=57 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=120 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=134 Participants 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.
Annualized Rate of Decrease in FVC Over 52 Weeks	-221.029 mL/year Standard Error 34.87511	-192.906 mL/year Standard Error 34.93853	-231.167 mL/year Standard Error 22.67786	-209.437 mL/year Standard Error 22.25073

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=58 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=62 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=136 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=144 Participants 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.
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	4.7886 units on a scale/year Standard Error 1.70370	5.6189 units on a scale/year Standard Error 0.99880	5.4558 units on a scale/year Standard Error 0.97793

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	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.	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.
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	48.7 percentage of participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	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.	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.
Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause	51.7 weeks Interval 24.1 to 54.6	52.3 weeks Interval 35.7 to Upper limit of 95% CI could not be estimated due to high number of censored participants.	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=172 Participants 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.
Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation	3.9 percentage of participants	3.9 percentage of participants	6.3 percentage of participants	2.9 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=172 Participants 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.
Time to First Event of Acute IPF Exacerbation	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=175 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=173 Participants 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.	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.	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.
Percentage of Participants With Respiratory-Related Hospitalization	15.4 percentage of participants	14.5 percentage of participants	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=175 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=173 Participants 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.	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.	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.
Time to Respiratory-Related Hospitalization	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=173 Participants 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.
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	6.6 percentage of participants	14.9 percentage of participants	11.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=76 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=76 Participants 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=175 Participants 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=173 Participants 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.
Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.	NA weeks Median and corresponding 95% CI could not be estimated due to high number of censored participants.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=75 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=172 Participants 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.	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.	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.
Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab Baseline	5.3 percentage of participants	1.8 percentage of participants	—	—
Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab Post-Baseline	6.7 percentage of participants	5.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: 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.

Participants who received lebrikizumab were only included in the analysis.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=62 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=137 Participants 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.	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.	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.
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52	29.6 micrograms per milliliter (mcg/mL) Standard Deviation 14.0	25.2 micrograms per milliliter (mcg/mL) Standard Deviation 12.7	—	—

SECONDARY outcome

Timeframe: 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.

Participants who received lebrikizumab were only included in the analysis.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=78 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=174 Participants 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.	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.	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.
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab Cmin at Week 4	14.0 mcg/mL Standard Deviation 4.86	14.9 mcg/mL Standard Deviation 5.75	—	—
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab Cmin at Week 12	24.4 mcg/mL Standard Deviation 9.86	25.0 mcg/mL Standard Deviation 11.0	—	—
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab Cmin at Week 24	28.5 mcg/mL Standard Deviation 12.5	25.7 mcg/mL Standard Deviation 12.4	—	—
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab Cmin at Week 36	29.9 mcg/mL Standard Deviation 14.1	25.6 mcg/mL Standard Deviation 13.8	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Monotherapy (Cohort A): Placebo n=35 Participants 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.	Monotherapy (Cohort A): Lebrikizumab n=125 Participants 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.	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.	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.
Elimination Half-Life (t1/2) of Lebrikizumab	23.5 days Standard Deviation 5.36	21.9 days Standard Deviation 4.79	—	—

Adverse Events

Monotherapy (Cohort A): Placebo

Serious events: 19 serious events

Other events: 70 other events

Deaths: 4 deaths

Monotherapy (Cohort A): Lebrikizumab

Serious events: 23 serious events

Other events: 73 other events

Deaths: 4 deaths

Combination Therapy (Cohort B): Placebo + Pirfenidone

Serious events: 47 serious events

Other events: 158 other events

Deaths: 15 deaths

Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone

Serious events: 56 serious events

Other events: 142 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Monotherapy (Cohort A): Placebo n=76 participants at risk 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.	Monotherapy (Cohort A): Lebrikizumab n=78 participants at risk 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.	Combination Therapy (Cohort B): Placebo + Pirfenidone n=177 participants at risk 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.	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone n=174 participants at risk 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.
Eye disorders Cataract	2.6% 2/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	4.0% 7/177 • Baseline up to Week 122 Safety Population	2.3% 4/174 • Baseline up to Week 122 Safety Population
Eye disorders Dry eye	0.00% 0/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	0.56% 1/177 • Baseline up to Week 122 Safety Population	1.7% 3/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Abdominal discomfort	2.6% 2/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	1.7% 3/177 • Baseline up to Week 122 Safety Population	1.7% 3/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Abdominal pain	3.9% 3/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	1.1% 2/177 • Baseline up to Week 122 Safety Population	0.57% 1/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Abdominal pain upper	5.3% 4/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	2.3% 4/177 • Baseline up to Week 122 Safety Population	3.4% 6/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Constipation	14.5% 11/76 • Baseline up to Week 122 Safety Population	14.1% 11/78 • Baseline up to Week 122 Safety Population	6.8% 12/177 • Baseline up to Week 122 Safety Population	8.0% 14/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Diarrhoea	21.1% 16/76 • Baseline up to Week 122 Safety Population	21.8% 17/78 • Baseline up to Week 122 Safety Population	13.0% 23/177 • Baseline up to Week 122 Safety Population	10.3% 18/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Dry mouth	0.00% 0/76 • Baseline up to Week 122 Safety Population	7.7% 6/78 • Baseline up to Week 122 Safety Population	1.1% 2/177 • Baseline up to Week 122 Safety Population	2.3% 4/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Dyspepsia	2.6% 2/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	2.8% 5/177 • Baseline up to Week 122 Safety Population	4.6% 8/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Flatulence	0.00% 0/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	0.56% 1/177 • Baseline up to Week 122 Safety Population	0.57% 1/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Gastrooesophageal reflux disease	2.6% 2/76 • Baseline up to Week 122 Safety Population	3.8% 3/78 • Baseline up to Week 122 Safety Population	5.1% 9/177 • Baseline up to Week 122 Safety Population	5.2% 9/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Nausea	13.2% 10/76 • Baseline up to Week 122 Safety Population	12.8% 10/78 • Baseline up to Week 122 Safety Population	13.0% 23/177 • Baseline up to Week 122 Safety Population	16.1% 28/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Toothache	5.3% 4/76 • Baseline up to Week 122 Safety Population	0.00% 0/78 • Baseline up to Week 122 Safety Population	1.1% 2/177 • Baseline up to Week 122 Safety Population	0.57% 1/174 • Baseline up to Week 122 Safety Population
Gastrointestinal disorders Vomiting	7.9% 6/76 • Baseline up to Week 122 Safety Population	3.8% 3/78 • Baseline up to Week 122 Safety Population	5.1% 9/177 • Baseline up to Week 122 Safety Population	4.6% 8/174 • Baseline up to Week 122 Safety Population
General disorders Asthenia	2.6% 2/76 • Baseline up to Week 122 Safety Population	6.4% 5/78 • Baseline up to Week 122 Safety Population	1.7% 3/177 • Baseline up to Week 122 Safety Population	0.00% 0/174 • Baseline up to Week 122 Safety Population
General disorders Chest discomfort	6.6% 5/76 • Baseline up to Week 122 Safety Population	2.6% 2/78 • Baseline up to Week 122 Safety Population	1.7% 3/177 • Baseline up to Week 122 Safety Population	1.7% 3/174 • Baseline up to Week 122 Safety Population
General disorders Chest pain	6.6% 5/76 • Baseline up to Week 122 Safety Population	9.0% 7/78 • Baseline up to Week 122 Safety Population	4.0% 7/177 • Baseline up to Week 122 Safety Population	5.7% 10/174 • Baseline up to Week 122 Safety Population
General disorders Fatigue	15.8% 12/76 • Baseline up to Week 122 Safety Population	19.2% 15/78 • Baseline up to Week 122 Safety Population	12.4% 22/177 • Baseline up to Week 122 Safety Population	16.1% 28/174 • Baseline up to Week 122 Safety Population
General disorders Injection site erythema	1.3% 1/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	0.56% 1/177 • Baseline up to Week 122 Safety Population	0.57% 1/174 • Baseline up to Week 122 Safety Population
General disorders Oedema peripheral	2.6% 2/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	2.3% 4/177 • Baseline up to Week 122 Safety Population	1.7% 3/174 • Baseline up to Week 122 Safety Population
General disorders Pain	2.6% 2/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	1.1% 2/177 • Baseline up to Week 122 Safety Population	0.57% 1/174 • Baseline up to Week 122 Safety Population
Infections and infestations Bronchitis	14.5% 11/76 • Baseline up to Week 122 Safety Population	19.2% 15/78 • Baseline up to Week 122 Safety Population	6.2% 11/177 • Baseline up to Week 122 Safety Population	9.8% 17/174 • Baseline up to Week 122 Safety Population
Infections and infestations Influenza	5.3% 4/76 • Baseline up to Week 122 Safety Population	6.4% 5/78 • Baseline up to Week 122 Safety Population	5.6% 10/177 • Baseline up to Week 122 Safety Population	1.7% 3/174 • Baseline up to Week 122 Safety Population
Infections and infestations Lower respiratory tract infection	6.6% 5/76 • Baseline up to Week 122 Safety Population	14.1% 11/78 • Baseline up to Week 122 Safety Population	7.3% 13/177 • Baseline up to Week 122 Safety Population	5.7% 10/174 • Baseline up to Week 122 Safety Population
Infections and infestations Nasopharyngitis	25.0% 19/76 • Baseline up to Week 122 Safety Population	21.8% 17/78 • Baseline up to Week 122 Safety Population	14.1% 25/177 • Baseline up to Week 122 Safety Population	17.8% 31/174 • Baseline up to Week 122 Safety Population
Infections and infestations Pneumonia	3.9% 3/76 • Baseline up to Week 122 Safety Population	1.3% 1/78 • Baseline up to Week 122 Safety Population	5.1% 9/177 • Baseline up to Week 122 Safety Population	1.7% 3/174 • Baseline up to Week 122 Safety Population
Infections and infestations Respiratory tract infection	6.6% 5/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	5.1% 9/177 • Baseline up to Week 122 Safety Population	4.6% 8/174 • Baseline up to Week 122 Safety Population
Infections and infestations Rhinitis	5.3% 4/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	4.0% 7/177 • Baseline up to Week 122 Safety Population	1.1% 2/174 • Baseline up to Week 122 Safety Population
Infections and infestations Sinusitis	6.6% 5/76 • Baseline up to Week 122 Safety Population	7.7% 6/78 • Baseline up to Week 122 Safety Population	5.1% 9/177 • Baseline up to Week 122 Safety Population	6.3% 11/174 • Baseline up to Week 122 Safety Population
Infections and infestations Upper respiratory tract infection	17.1% 13/76 • Baseline up to Week 122 Safety Population	23.1% 18/78 • Baseline up to Week 122 Safety Population	21.5% 38/177 • Baseline up to Week 122 Safety Population	17.8% 31/174 • Baseline up to Week 122 Safety Population
Infections and infestations Urinary tract infection	6.6% 5/76 • Baseline up to Week 122 Safety Population	11.5% 9/78 • Baseline up to Week 122 Safety Population	6.2% 11/177 • Baseline up to Week 122 Safety Population	3.4% 6/174 • Baseline up to Week 122 Safety Population
Injury, poisoning and procedural complications Fall	7.9% 6/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	1.7% 3/177 • Baseline up to Week 122 Safety Population	3.4% 6/174 • Baseline up to Week 122 Safety Population
Investigations Forced vital capacity decreased	5.3% 4/76 • Baseline up to Week 122 Safety Population	14.1% 11/78 • Baseline up to Week 122 Safety Population	3.4% 6/177 • Baseline up to Week 122 Safety Population	3.4% 6/174 • Baseline up to Week 122 Safety Population
Investigations Weight decreased	6.6% 5/76 • Baseline up to Week 122 Safety Population	2.6% 2/78 • Baseline up to Week 122 Safety Population	5.1% 9/177 • Baseline up to Week 122 Safety Population	6.3% 11/174 • Baseline up to Week 122 Safety Population
Metabolism and nutrition disorders Decreased appetite	6.6% 5/76 • Baseline up to Week 122 Safety Population	11.5% 9/78 • Baseline up to Week 122 Safety Population	12.4% 22/177 • Baseline up to Week 122 Safety Population	9.8% 17/174 • Baseline up to Week 122 Safety Population
Musculoskeletal and connective tissue disorders Arthralgia	11.8% 9/76 • Baseline up to Week 122 Safety Population	11.5% 9/78 • Baseline up to Week 122 Safety Population	4.5% 8/177 • Baseline up to Week 122 Safety Population	5.7% 10/174 • Baseline up to Week 122 Safety Population
Musculoskeletal and connective tissue disorders Back pain	11.8% 9/76 • Baseline up to Week 122 Safety Population	15.4% 12/78 • Baseline up to Week 122 Safety Population	6.2% 11/177 • Baseline up to Week 122 Safety Population	6.3% 11/174 • Baseline up to Week 122 Safety Population
Musculoskeletal and connective tissue disorders Muscle spasms	6.6% 5/76 • Baseline up to Week 122 Safety Population	7.7% 6/78 • Baseline up to Week 122 Safety Population	2.3% 4/177 • Baseline up to Week 122 Safety Population	1.1% 2/174 • Baseline up to Week 122 Safety Population
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.3% 1/76 • Baseline up to Week 122 Safety Population	6.4% 5/78 • Baseline up to Week 122 Safety Population	1.1% 2/177 • Baseline up to Week 122 Safety Population	0.57% 1/174 • Baseline up to Week 122 Safety Population
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.2% 10/76 • Baseline up to Week 122 Safety Population	6.4% 5/78 • Baseline up to Week 122 Safety Population	4.5% 8/177 • Baseline up to Week 122 Safety Population	1.1% 2/174 • Baseline up to Week 122 Safety Population
Nervous system disorders Dizziness	13.2% 10/76 • Baseline up to Week 122 Safety Population	17.9% 14/78 • Baseline up to Week 122 Safety Population	7.9% 14/177 • Baseline up to Week 122 Safety Population	6.3% 11/174 • Baseline up to Week 122 Safety Population
Nervous system disorders Headache	11.8% 9/76 • Baseline up to Week 122 Safety Population	12.8% 10/78 • Baseline up to Week 122 Safety Population	9.6% 17/177 • Baseline up to Week 122 Safety Population	6.3% 11/174 • Baseline up to Week 122 Safety Population
Psychiatric disorders Anxiety	6.6% 5/76 • Baseline up to Week 122 Safety Population	3.8% 3/78 • Baseline up to Week 122 Safety Population	0.56% 1/177 • Baseline up to Week 122 Safety Population	1.1% 2/174 • Baseline up to Week 122 Safety Population
Psychiatric disorders Insomnia	3.9% 3/76 • Baseline up to Week 122 Safety Population	9.0% 7/78 • Baseline up to Week 122 Safety Population	2.3% 4/177 • Baseline up to Week 122 Safety Population	4.6% 8/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Cough	25.0% 19/76 • Baseline up to Week 122 Safety Population	26.9% 21/78 • Baseline up to Week 122 Safety Population	26.0% 46/177 • Baseline up to Week 122 Safety Population	19.0% 33/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	0.56% 1/177 • Baseline up to Week 122 Safety Population	0.00% 0/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.8% 12/76 • Baseline up to Week 122 Safety Population	17.9% 14/78 • Baseline up to Week 122 Safety Population	10.2% 18/177 • Baseline up to Week 122 Safety Population	7.5% 13/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.3% 4/76 • Baseline up to Week 122 Safety Population	7.7% 6/78 • Baseline up to Week 122 Safety Population	2.3% 4/177 • Baseline up to Week 122 Safety Population	2.9% 5/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	17.1% 13/76 • Baseline up to Week 122 Safety Population	14.1% 11/78 • Baseline up to Week 122 Safety Population	5.6% 10/177 • Baseline up to Week 122 Safety Population	5.2% 9/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.2% 7/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	2.8% 5/177 • Baseline up to Week 122 Safety Population	1.1% 2/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Productive cough	3.9% 3/76 • Baseline up to Week 122 Safety Population	10.3% 8/78 • Baseline up to Week 122 Safety Population	4.5% 8/177 • Baseline up to Week 122 Safety Population	3.4% 6/174 • Baseline up to Week 122 Safety Population
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.3% 1/76 • Baseline up to Week 122 Safety Population	6.4% 5/78 • Baseline up to Week 122 Safety Population	0.56% 1/177 • Baseline up to Week 122 Safety Population	1.1% 2/174 • Baseline up to Week 122 Safety Population
Skin and subcutaneous tissue disorders Photosensitivity reaction	7.9% 6/76 • Baseline up to Week 122 Safety Population	3.8% 3/78 • Baseline up to Week 122 Safety Population	13.6% 24/177 • Baseline up to Week 122 Safety Population	4.0% 7/174 • Baseline up to Week 122 Safety Population
Skin and subcutaneous tissue disorders Pruritus	2.6% 2/76 • Baseline up to Week 122 Safety Population	3.8% 3/78 • Baseline up to Week 122 Safety Population	6.8% 12/177 • Baseline up to Week 122 Safety Population	4.6% 8/174 • Baseline up to Week 122 Safety Population
Skin and subcutaneous tissue disorders Rash	6.6% 5/76 • Baseline up to Week 122 Safety Population	11.5% 9/78 • Baseline up to Week 122 Safety Population	11.9% 21/177 • Baseline up to Week 122 Safety Population	10.3% 18/174 • Baseline up to Week 122 Safety Population
Vascular disorders Hypertension	5.3% 4/76 • Baseline up to Week 122 Safety Population	5.1% 4/78 • Baseline up to Week 122 Safety Population	2.3% 4/177 • Baseline up to Week 122 Safety Population	4.0% 7/174 • Baseline up to Week 122 Safety Population
General disorders Pyrexia	2.6% 2/76 • Baseline up to Week 122 Safety Population	7.7% 6/78 • Baseline up to Week 122 Safety Population	2.8% 5/177 • Baseline up to Week 122 Safety Population	0.57% 1/174 • Baseline up to Week 122 Safety Population