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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01872689
• Collaborator: (none)
• Enrollment: 505
• Locations: 112
• Arms: 4
• Actual Duration (Months): 48.8
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Lebrikizumab; Drug: Pirfenidone; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 505 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Idiopathic Pulmonary Fibrosis
• Actual Study Start Date: Oct 13, 2013
• Actual Primary Completion Date: Jul 28, 2017
• Actual Study Completion Date: Nov 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Monotherapy (Cohort A): Placebo Participants will receive monotherapy with placebo matched to lebrikizumab administered via subcutaneous (SC) injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants will be allowed to receive treatment with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to additional 52 weeks (that is, up to Week 104) in the open-label period.	Drug: Lebrikizumab; Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.; Other Names: RO5490255 ; Drug: Placebo; Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.
Experimental: Monotherapy (Cohort A): Lebrikizumab Participants will receive monotherapy with lebrikizumab at a dose of 250 milligrams (mg) administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants will be allowed to receive treatment with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to additional 52 weeks (that is, up to Week 104) in the open-label period.	Drug: Lebrikizumab; Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.; Other Names: RO5490255
Placebo Comparator: Combination Therapy (Cohort B): Placebo + Pirfenidone Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day [9 capsules daily] for a total of 2403 mg/day) or at maximum tolerated dose (MTD) administered orally along with placebo matched to lebrikizumab administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.	Drug: Pirfenidone; Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.; Drug: Placebo; Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.
Experimental: Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day [9 capsules daily] for a total of 2403 mg/day) or at MTD administered orally along with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.	Drug: Lebrikizumab; Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.; Other Names: RO5490255 ; Drug: Pirfenidone; Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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).

12. 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.

13. Percentage of Participants With Respiratory-Related Hospitalization [Baseline up to the event of respiratory-related hospitalization (up to Week 122)]

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Alabama At Birmingham	Birmingham	Alabama	United States	35294
2	Mayo Clinic- Scottsdale	Scottsdale	Arizona	United States	85259
3	Southern Arizona Veterans Administration Healthcare Systems	Tucson	Arizona	United States	85723
4	University of Arizona	Tucson	Arizona	United States	85724-5030
5	UCSD Medical Center	La Jolla	California	United States	92093
6	University of California, San Francisco	San Francisco	California	United States	94116
7	National Jewish Health	Denver	Colorado	United States	80206
8	Rocky Mountain Center For Clinical Research	Wheat Ridge	Colorado	United States	80033
9	Yale New Haven Hospital	New Haven	Connecticut	United States	06520
10	Research Alliance Inc	Clearwater	Florida	United States	33756
11	Mayo Clinic-Jacksonville	Jacksonville	Florida	United States	32224
12	University Miami	Miami	Florida	United States	33136
13	Central Florida Pulmonary Group, PA	Orlando	Florida	United States	32803
14	USF Tampa General Hospital	Tampa	Florida	United States	33606
15	Cleveland Clinic Florida	Weston	Florida	United States	33331
16	Piedmont Healthcare Pulmonary and Critical Care Research	Austell	Georgia	United States	30106
17	Southeastern Lung Care	Decatur	Georgia	United States	30033
18	University of Chicago; Pulmonary and Critical Care	Chicago	Illinois	United States	60637
19	Loyola University Med Center	Maywood	Illinois	United States	60153
20	Univ of Iowa Hosp & Clinics; Pulmonary	Iowa City	Iowa	United States	52242
21	Uni of Kansas Medical Center	Kansas	Kansas	United States	66160
22	Via Christi Hospital Inc. DBA Via Christi Research; Research Dept.	Wichita	Kansas	United States	67208
23	Maine Medical Center -Division of Pulmomary and Critical Care Medicine	Portland	Maine	United States	04106
24	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
25	Johns Hopkins Bayview Medical Center - Johns Hopkins Asthma & Allergy Center	Baltimore	Maryland	United States	21224
26	Tufts Medical Center	Boston	Massachusetts	United States	02111
27	University of Minnesota Hospital & Clinic	Minneapolis	Minnesota	United States	55455
28	Mayo Clinic Rochester	Rochester	Minnesota	United States	55902
29	Cardiopulmonary Associates LLC Cardiopulmonary Research	Chesterfield	Missouri	United States	63017
30	University of Nebraska	Omaha	Nebraska	United States	68198-5300
31	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico	United States	87108
32	Weill Medical College of Cornell University	New York	New York	United States	10021-5663
33	Mt Sinai School Medical Pulmo And Critical Care Med	New York	New York	United States	10029
34	Highland Hospital-University of Rochester Medical Center	Rochester	New York	United States	14620
35	University of Cincinnati	Cincinnati	Ohio	United States	45203-0542
36	Case Western Research University; University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106-5067
37	Ohio State University	Columbus	Ohio	United States	43210
38	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
39	The Oregon Clinic.	Portland	Oregon	United States	97220
40	Penn State University College Medical Allergy And Care Med	Hershey	Pennsylvania	United States	17033
41	Temple Lung Center, Temple Universtiy-Of the Commomwealth System of Higher Education	Philadelphia	Pennsylvania	United States	19140
42	University of Pittsburgh Med Cen; Dorothy P And Richard P Simmons Cen For Interstitial Lung Disease	Pittsburgh	Pennsylvania	United States	15213
43	Rhode Island Hospital	Providence	Rhode Island	United States	02903
44	Medical University of South Carolina	Charleston	South Carolina	United States	29425
45	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
46	Baylor College Med	Houston	Texas	United States	77030
47	Houston Methodist Hospital	Houston	Texas	United States	77030
48	Audie Murphy Va Hospital	San Antonio	Texas	United States	78229
49	University of Utah Health Sciences Center, Lung Health Research Center	Salt Lake City	Utah	United States	84108
50	University Vermont College Medicine Fletcher Allen Health Care	Colchester	Vermont	United States	05446
51	Inova Transplant Center Fairfax Hospital	Falls Church	Virginia	United States	22042
52	Pulmonary Consultants	Tacoma	Washington	United States	98405
53	University Wisconsin Hospitals and Clinics	Madison	Wisconsin	United States	53792
54	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
55	Royal Prince Alfred Hospital; Department of Respiratory Medicine	Camperdown	New South Wales	Australia	2050
56	ST VINCENT'S HOSPITAL; Thoracic Medicine	Darlinghurst	New South Wales	Australia	2010
57	Box Hill Hospital; Eastern Clinical Research Unit	Box Hill	Victoria	Australia	3128
58	Alfred Hospital; Allergy Immuno Resp	Melbourne	Victoria	Australia	3004
59	Institute for Respiratory Health Inc	Nedlands	Western Australia	Australia	6009
60	Hospital Erasme; Neurologie	Bruxelles		Belgium	1070
61	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
62	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
63	CHU UCL Mont-Godinne	Mont-godinne		Belgium	5530
64	University of British Columbia - Vancouver Coastal Health Authority	Vancouver	British Columbia	Canada	V5Z 1M9
65	Dr. Georges-L. Dumont Regional Hospital	Moncton	New Brunswick	Canada	E1G 2K5
66	St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada	L8N4A6
67	Lawson Health Research Institute a joint venture of LHSC Research Inc and Lawson Research Institute	London	Ontario	Canada	N6C 2R5
68	Institut universitaire de cardiologie et de pneumologie de Québec (Hôpital Laval)	Ste. Foy	Quebec	Canada	G1V 4G5
69	Hopital Avicenne; Pneumologie	Bobigny		France	93000
70	Hopital Louis Pradel; Pneumologie	Bron		France	69677
71	Hopital Calmette; Pneumologie	Lille		France	59037
72	Hopital Bichat Claude Bernard ; Service de Pneumologie	Paris		France	75877
73	Hopital de Pontchaillou; Service de Pneumologie	Rennes		France	35033
74	Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie	Essen		Germany	45239
75	Universitätsklinikum Standort Gießen Medizinische Klinik II u. Poliklinik Innere Med./Pneumologie	Gießen		Germany	35392
76	LungenClinic Großhansdorf	Großhansdorf		Germany	22927
77	Thoraxklinik Heidelberg gGmbH	Heidelberg		Germany	69126
78	Fachklinik für Lungenerkrankungen	Immenhausen		Germany	34376
79	CPC Comprehensive Pneumology Center / Forschungsambulanz, Helmholtz Zentrum	München		Germany	81377
80	Ospedale Morgagni-Pierantoni; U.O. Pneumologia	Forlì	Emilia-Romagna	Italy	47121
81	Policlinico Tor Vergata; UO Mal. Respiratorie; Centro Malattie rare polmone	Roma	Lazio	Italy	00133
82	Ospedale San Giuseppe; U.O. di Pneumologia	Milano	Lombardia	Italy	20123
83	A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone	Orbassano (TO)	Piemonte	Italy	10043
84	A.O.U. Policlinico Vittorio Emanuele; Centro per la cura delle Malattie Rare del Polmone	Catania	Sicilia	Italy	95123
85	A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare	Siena	Toscana	Italy	53100
86	Kanagawa Cardiovascular and Respiratory Center; Respiratory Medicine	Kanagawa		Japan	236-0051
87	Kinki-Chuo Chest Medical Center	Osaka		Japan	591-8555
88	Tosei General Hospital	Seto-shi		Japan	489-8642
89	Hospital General Del Estado De Sonora "Dr. Ernesto Ramos Bours"; Servicio De Neumologia	Hermosillo		Mexico	83000
90	Instituto Nacional De Enfermedades Respiratorias;Unidad de Investigación	Mexico City		Mexico	14080
91	Universidad Autonoma De Nuevo Leon, Hospital Universitario Doctor Jose Eleuterio Gonzalez	Monterrey		Mexico	64460
92	Unidad de Investigacion Clinica En Medicina (Udicem) S.C.	Monterrey		Mexico	64718
93	Clinica San Pablo	Lima		Peru	Lima 33
94	Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional	Lima		Peru	Lima 41
95	Clinica San Borja; NEUMOCARE	Lima		Peru	Lima 41
96	Uniwersytecki Szpital Kliniczny Nr 1 im.N.Barlickiego Oddzial Kliniczny Pneumonologii i Alergologii	Lodz		Poland	90-153
97	Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej	Lublin		Poland	20-064
98	Klinika Pulmonologii, Alergologii i Onkologii Pulmonologicznej Uniwersytet Medyczny w Poznaniu	Poznan		Poland	60-569
99	Instytut Gruzlicy i Chorob Płuc	Warszawa		Poland	01-138
100	Klinika Chorob Pluc i Gruzlicy w Zabrzu; Slaski Uniwersytet Medyczny	Zabrze		Poland	41-803
101	Hospital Universitari de Bellvitge ; Servicio de Neumologia	Hospitalet de Llobregat	Barcelona	Spain	08097
102	Hospital Universitario La Princesa; Servicio de Neumologia	Madrid		Spain	28006
103	Hospital Clínico San Carlos - Servicio de Neumologia	Madrid		Spain	28040
104	Hospital Universitario Virgen del Rocio; Servicio de Neumologia	Sevilla		Spain	41013
105	Hospital General Universitario De Valencia; Servicio de Neumologia	Valencia		Spain	46014
106	Southmead Hospital; Respiratory Department	Bristol		United Kingdom	BS10-5NB
107	Papworth Hospital NHS Foundation Trust; Respiratory Department	Cambridge		United Kingdom	CB23 3RE
108	Southampton General Hospital; Respiratory Department	Hampshire		United Kingdom	SO16 6YD
109	St James University Hospital; Respiratory Department	Leeds		United Kingdom	LS9 7TF
110	Respiratory research department clinical science building	Liverpool		United Kingdom	L9 7AL
111	Royal Brompton Hospital; Respiratory Department	London		United Kingdom	SW3 6NP
112	North Manchester Hospital; Respiratory Department	Manchester		United Kingdom	M8 5RB

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 23, 2016

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01872689
• Other Study ID Numbers: GB28547; 2013-001163-24
• First Posted: Jun 7, 2013
• Last Update Posted: Aug 24, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pirfenidone

Study Results

Participant Flow

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

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Period Title: Double-Blind/Placebo-Controlled Period
STARTED	76	78	177	174
COMPLETED	56	58	129	136
NOT COMPLETED	20	20	48	38
Period Title: Double-Blind/Placebo-Controlled Period
STARTED	52	56	0	0
COMPLETED	31	33	0	0
NOT COMPLETED	21	23	0	0

Baseline Characteristics

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone	Total
Arm/Group Description	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.	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.	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.	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 of all reporting groups
Overall Participants	76	78	177	174	505
Age, Customized (participants) [Number]
From 40 to <55 years	2 2.6%	1 1.3%	6 3.4%	2 1.1%	11 2.2%
From 55 to <65 years	18 23.7%	10 12.8%	40 22.6%	41 23.6%	109 21.6%
From 65 to <75 years	38 50%	44 56.4%	99 55.9%	92 52.9%	273 54.1%
>/=75 years	18 23.7%	23 29.5%	32 18.1%	39 22.4%	112 22.2%
Sex: Female, Male (Count of Participants)
Female	13 17.1%	13 16.7%	30 16.9%	37 21.3%	93 18.4%
Male	63 82.9%	65 83.3%	147 83.1%	137 78.7%	412 81.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 11.8%	6 7.7%	13 7.3%	15 8.6%	43 8.5%
Not Hispanic or Latino	64 84.2%	68 87.2%	160 90.4%	155 89.1%	447 88.5%
Unknown or Not Reported	3 3.9%	4 5.1%	4 2.3%	4 2.3%	15 3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.3%	1 1.3%	0 0%	1 0.6%	3 0.6%
Asian	11 14.5%	8 10.3%	19 10.7%	15 8.6%	53 10.5%
Native Hawaiian or Other Pacific Islander	1 1.3%	0 0%	1 0.6%	0 0%	2 0.4%
Black or African American	0 0%	0 0%	1 0.6%	1 0.6%	2 0.4%
White	60 78.9%	66 84.6%	149 84.2%	151 86.8%	426 84.4%
More than one race	0 0%	1 1.3%	0 0%	0 0%	1 0.2%
Unknown or Not Reported	3 3.9%	2 2.6%	7 4%	6 3.4%	18 3.6%

Outcome Measures

1. Primary Outcome

Title	Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	53	56	120	134
Mean (Standard Error) [percent predicted FVC/year]	-6.1876 (0.92597)	-5.2065 (0.92758)	-6.0430 (0.60633)	-5.5430 (0.59507)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4555
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.98111
	Confidence Interval	(2-Sided) 95%; -1.61 to 3.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.31064
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5566
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.49998
	Confidence Interval	(2-Sided) 95%; -1.17 to 2.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.84946
	Estimation Comments

2. Secondary Outcome

Title	Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	52	59	120	129
Mean (Standard Error) [m/year]	-44.6512 (15.97862)	-22.7209 (15.34753)	-25.5683 (12.24923)	-46.9810 (11.84199)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3129
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	21.93023
	Confidence Interval	(2-Sided) 95%; -20.97 to 64.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 21.62248
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2036
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-21.4127
	Confidence Interval	(2-Sided) 95%; -54.50 to 11.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 16.80160
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	173
Number [percentage of participants]	34.2 45%	27.6 35.4%	30.3 17.1%	26.6 15.3%

4. Secondary Outcome

Title	Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	173
Median (95% Confidence Interval) [weeks]	53.1	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4299
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3751
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	50	52	112	122
Mean (Standard Error) [mL/min/mmHg/year]	-4.7818 (0.74479)	-4.2400 (0.73826)	-5.7552 (0.46561)	-5.5732 (0.45577)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6075
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.54171
	Confidence Interval	(2-Sided) 95%; -1.54 to 2.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.05201
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7803
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.18203
	Confidence Interval	(2-Sided) 95%; -1.10 to 1.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.65206
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	173
Number [percentage of participants]	47.4 62.4%	32.9 42.2%	39.4 22.3%	39.9 22.9%

7. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	173
Median (95% Confidence Interval) [weeks]	52.6	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0972
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9344
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Annualized Rate of Decrease in FVC Over 52 Weeks
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	53	57	120	134
Mean (Standard Error) [mL/year]	-221.029 (34.87511)	-192.906 (34.93853)	-231.167 (22.67786)	-209.437 (22.25073)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5707
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	28.12302
	Confidence Interval	(2-Sided) 95%; -69.80 to 126.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 49.47253
	Estimation Comments	Mean Difference = Lebrikizumab - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4934
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.72972
	Confidence Interval	(2-Sided) 95%; -40.65 to 84.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 31.68767
	Estimation Comments	Mean Difference = Lebrikizumab - Placebo

9. Secondary Outcome

Title	Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	58	62	136	144
Mean (Standard Error) [units on a scale/year]	6.8907 (1.71778)	4.7886 (1.70370)	5.6189 (0.99880)	5.4558 (0.97793)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3854
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-2.10204
	Confidence Interval	(2-Sided) 95%; -6.88 to 2.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.41325
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9057
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.16313
	Confidence Interval	(2-Sided) 95%; -2.87 to 2.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.37698
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab
Arm/Group Description	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.	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.
Measure Participants	76	76
Number [percentage of participants]	57.9 76.2%	48.7 62.4%

11. Secondary Outcome

Title	Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab
Arm/Group Description	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.	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.
Measure Participants	76	76
Median (95% Confidence Interval) [weeks]	51.7	52.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4433
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	172
Number [percentage of participants]	3.9 5.1%	3.9 5%	6.3 3.6%	2.9 1.7%

13. Secondary Outcome

Title	Time to First Event of Acute IPF Exacerbation
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	172
Median (95% Confidence Interval) [weeks]	NA	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9366
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.21 to 5.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1346
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; 0.16 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants With Respiratory-Related Hospitalization
Time Frame	Baseline up to the event of respiratory-related hospitalization (up to Week 122)

Outcome Measure Data

Analysis Population Description

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/Group Title	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.
Measure Participants	175	173
Number [percentage of participants]	15.4 20.3%	14.5 18.6%

15. Secondary Outcome

Title	Time to Respiratory-Related Hospitalization
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.
Measure Participants	175	173
Median (95% Confidence Interval) [weeks]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6815
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	173
Number [percentage of participants]	9.2 12.1%	6.6 8.5%	14.9 8.4%	11.0 6.3%

17. Secondary Outcome

Title	Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Placebo	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Placebo + Pirfenidone	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.	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.	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.
Measure Participants	76	76	175	173
Median (95% Confidence Interval) [weeks]	NA	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monotherapy (Cohort A): Placebo, Monotherapy (Cohort A): Lebrikizumab
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5685
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.23 to 2.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination Therapy (Cohort B): Placebo + Pirfenidone, Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Comments	Stratified Analysis: stratified by baseline FVC (<50%, 50 to 75%, >75%)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1976
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.37 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.
Measure Participants	75	172
Baseline	5.3 7%	1.8 2.3%
Post-Baseline	6.7 8.8%	5.2 6.7%

19. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52
Description	Participants who received lebrikizumab were only included in the analysis.
Time Frame	Predose (Hour 0) at Week 52

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.
Measure Participants	62	137
Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]	29.6 (14.0)	25.2 (12.7)

20. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Lebrikizumab
Description	Participants who received lebrikizumab were only included in the analysis.
Time Frame	Predose (Hour 0) at Weeks 4, 12, 24, and 36

Outcome Measure Data

Analysis Population Description

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/Group Title	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.
Measure Participants	78	174
Cmin at Week 4	14.0 (4.86)	14.9 (5.75)
Cmin at Week 12	24.4 (9.86)	25.0 (11.0)
Cmin at Week 24	28.5 (12.5)	25.7 (12.4)
Cmin at Week 36	29.9 (14.1)	25.6 (13.8)

21. Secondary Outcome

Title	Elimination Half-Life (t1/2) of Lebrikizumab
Description	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK-Evaluable Population. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Monotherapy (Cohort A): Lebrikizumab	Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.	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.
Measure Participants	35	125
Mean (Standard Deviation) [days]	23.5 (5.36)	21.9 (4.79)

Adverse Events

Time Frame	Baseline up to Week 122
Adverse Event Reporting Description	Safety Population
Arm/Group Title	Monotherapy (Cohort A): Placebo		Monotherapy (Cohort A): Lebrikizumab		Combination Therapy (Cohort B): Placebo + Pirfenidone		Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Monotherapy (Cohort A): Placebo		Monotherapy (Cohort A): Lebrikizumab		Combination Therapy (Cohort B): Placebo + Pirfenidone		Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/76 (5.3%)		4/78 (5.1%)		15/177 (8.5%)		7/174 (4%)
Serious Adverse Events
	Monotherapy (Cohort A): Placebo		Monotherapy (Cohort A): Lebrikizumab		Combination Therapy (Cohort B): Placebo + Pirfenidone		Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/76 (25%)		23/78 (29.5%)		47/177 (26.6%)		56/174 (32.2%)
Cardiac disorders
Acute coronary syndrome	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Acute myocardial infarction	1/76 (1.3%)		1/78 (1.3%)		0/177 (0%)		1/174 (0.6%)
Angina pectoris	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Atrial fibrillation	0/76 (0%)		1/78 (1.3%)		2/177 (1.1%)		1/174 (0.6%)
Atrial flutter	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Atrioventricular block	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Atrioventricular block second degree	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Bradycardia	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Cardiac arrest	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Cardio-respiratory arrest	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Cardiac failure	0/76 (0%)		2/78 (2.6%)		3/177 (1.7%)		1/174 (0.6%)
Cardiomegaly	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Coronary artery disease	2/76 (2.6%)		0/78 (0%)		2/177 (1.1%)		2/174 (1.1%)
Coronary artery occlusion	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Myocardial ischaemia	0/76 (0%)		1/78 (1.3%)		3/177 (1.7%)		0/174 (0%)
Right ventricular failure	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Tachycardia	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Ear and labyrinth disorders
Vertigo positional	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Gastrointestinal disorders
Diarrhoea	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Diverticulum intestinal haemorrhagic	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Gastritis	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Gastrooesophageal reflux disease	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Inguinal hernia	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Intestinal prolapse	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Mesenteric vein thrombosis	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Nausea	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Pancreatitis	0/76 (0%)		0/78 (0%)		0/177 (0%)		2/174 (1.1%)
Pancreatitis acute	2/76 (2.6%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Toothache	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Vomiting	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
General disorders
Chest pain	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Death	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Multiple organ dysfunction syndrome	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Sudden death	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Hepatobiliary disorders
Drug-induced liver injury	0/76 (0%)		0/78 (0%)		0/177 (0%)		2/174 (1.1%)
Immune system disorders
Graft versus host disease	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Infections and infestations
Bronchitis	0/76 (0%)		1/78 (1.3%)		1/177 (0.6%)		0/174 (0%)
Bronchitis bacterial	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Bronchopulmonary aspergillosis	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Campylobacter infection	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Diverticulitis	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Erysipelas	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Fungal infection	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
H1N1 influenza	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Influenza	1/76 (1.3%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Lower respiratory tract infection	1/76 (1.3%)		4/78 (5.1%)		2/177 (1.1%)		1/174 (0.6%)
Lung infection	0/76 (0%)		1/78 (1.3%)		1/177 (0.6%)		2/174 (1.1%)
Pneumonia	2/76 (2.6%)		3/78 (3.8%)		7/177 (4%)		7/174 (4%)
Pneumonia bacterial	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Pneumonia haemophilus	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Pneumonia influenzal	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Pneumonia viral	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Postoperative wound infection	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Respiratory syncytial virus infection	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Respiratory tract infection	1/76 (1.3%)		1/78 (1.3%)		3/177 (1.7%)		5/174 (2.9%)
Sepsis	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Septic shock	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		1/174 (0.6%)
Urinary tract infection enterococcal	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Wound infection bacterial	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Mycobacterium avium complex infection	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Urinary tract infection	0/76 (0%)		2/78 (2.6%)		0/177 (0%)		0/174 (0%)
Injury, poisoning and procedural complications
Fall	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Procedural hypotension	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Procedural pain	1/76 (1.3%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Radius fracture	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Spinal fracture	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Investigations
Blood creatine phosphokinase increased	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Hepatic enzyme increased	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Metabolism and nutrition disorders
Decreased appetite	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Dehydration	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Hypercalcaemia	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Hyponatraemia	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Musculoskeletal chest pain	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Musculoskeletal pain	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Rheumatoid arthritis	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		1/174 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Basosquamous carcinoma	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Chondrosarcoma	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Hepatic cancer	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Hepatocellular carcinoma	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Lung Adenocarcinoma Stage IV	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Lung Neoplasm	0/76 (0%)		1/78 (1.3%)		1/177 (0.6%)		0/174 (0%)
Lung neoplasm malignant	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Lung squamous cell carcinoma Stage 0	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Neuroendocrine carcinoma	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Pancreatic carcinoma metastatic	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Plasma cell myeloma	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Squamous cell carcinoma	0/76 (0%)		1/78 (1.3%)		3/177 (1.7%)		1/174 (0.6%)
Squamous cell carcinoma of skin	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Nervous system disorders
Carotid artery stenosis	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Cerebrovascular accident	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Epilepsy	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Ischaemic stroke	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Presyncope	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Syncope	1/76 (1.3%)		1/78 (1.3%)		1/177 (0.6%)		1/174 (0.6%)
Psychiatric disorders
Delirium	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/76 (2.6%)		1/78 (1.3%)		1/177 (0.6%)		1/174 (0.6%)
Haemoptysis	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Hyperventilation	0/76 (0%)		1/78 (1.3%)		0/177 (0%)		0/174 (0%)
Hypoxia	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		3/174 (1.7%)
Idiopathic pulmonary fibrosis	13/76 (17.1%)		11/78 (14.1%)		22/177 (12.4%)		17/174 (9.8%)
Oropharyngeal discomfort	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Pleural effusion	0/76 (0%)		1/78 (1.3%)		1/177 (0.6%)		0/174 (0%)
Pneumomediastinum	2/76 (2.6%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Pneumothorax	2/76 (2.6%)		2/78 (2.6%)		0/177 (0%)		1/174 (0.6%)
Pulmonary arterial hypertension	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Pulmonary embolism	3/76 (3.9%)		2/78 (2.6%)		1/177 (0.6%)		2/174 (1.1%)
Pulmonary fibrosis	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		1/174 (0.6%)
Pulmonary hypertension	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Respiratory failure	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Dyspnoea	2/76 (2.6%)		1/78 (1.3%)		1/177 (0.6%)		1/174 (0.6%)
Skin and subcutaneous tissue disorders
Angioedema	0/76 (0%)		0/78 (0%)		1/177 (0.6%)		0/174 (0%)
Vascular disorders
Aortic aneurysm	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Aortic stenosis	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Axillary vein thrombosis	1/76 (1.3%)		0/78 (0%)		0/177 (0%)		0/174 (0%)
Hypotension	0/76 (0%)		0/78 (0%)		0/177 (0%)		2/174 (1.1%)
Orthostatic hypotension	0/76 (0%)		0/78 (0%)		0/177 (0%)		1/174 (0.6%)
Other (Not Including Serious) Adverse Events
	Monotherapy (Cohort A): Placebo		Monotherapy (Cohort A): Lebrikizumab		Combination Therapy (Cohort B): Placebo + Pirfenidone		Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/76 (92.1%)		73/78 (93.6%)		158/177 (89.3%)		142/174 (81.6%)
Eye disorders
Cataract	2/76 (2.6%)		4/78 (5.1%)		7/177 (4%)		4/174 (2.3%)
Dry eye	0/76 (0%)		4/78 (5.1%)		1/177 (0.6%)		3/174 (1.7%)
Gastrointestinal disorders
Abdominal discomfort	2/76 (2.6%)		4/78 (5.1%)		3/177 (1.7%)		3/174 (1.7%)
Abdominal pain	3/76 (3.9%)		4/78 (5.1%)		2/177 (1.1%)		1/174 (0.6%)
Abdominal pain upper	4/76 (5.3%)		4/78 (5.1%)		4/177 (2.3%)		6/174 (3.4%)
Constipation	11/76 (14.5%)		11/78 (14.1%)		12/177 (6.8%)		14/174 (8%)
Diarrhoea	16/76 (21.1%)		17/78 (21.8%)		23/177 (13%)		18/174 (10.3%)
Dry mouth	0/76 (0%)		6/78 (7.7%)		2/177 (1.1%)		4/174 (2.3%)
Dyspepsia	2/76 (2.6%)		4/78 (5.1%)		5/177 (2.8%)		8/174 (4.6%)
Flatulence	0/76 (0%)		4/78 (5.1%)		1/177 (0.6%)		1/174 (0.6%)
Gastrooesophageal reflux disease	2/76 (2.6%)		3/78 (3.8%)		9/177 (5.1%)		9/174 (5.2%)
Nausea	10/76 (13.2%)		10/78 (12.8%)		23/177 (13%)		28/174 (16.1%)
Toothache	4/76 (5.3%)		0/78 (0%)		2/177 (1.1%)		1/174 (0.6%)
Vomiting	6/76 (7.9%)		3/78 (3.8%)		9/177 (5.1%)		8/174 (4.6%)
General disorders
Asthenia	2/76 (2.6%)		5/78 (6.4%)		3/177 (1.7%)		0/174 (0%)
Chest discomfort	5/76 (6.6%)		2/78 (2.6%)		3/177 (1.7%)		3/174 (1.7%)
Chest pain	5/76 (6.6%)		7/78 (9%)		7/177 (4%)		10/174 (5.7%)
Fatigue	12/76 (15.8%)		15/78 (19.2%)		22/177 (12.4%)		28/174 (16.1%)
Injection site erythema	1/76 (1.3%)		4/78 (5.1%)		1/177 (0.6%)		1/174 (0.6%)
Oedema peripheral	2/76 (2.6%)		4/78 (5.1%)		4/177 (2.3%)		3/174 (1.7%)
Pain	2/76 (2.6%)		4/78 (5.1%)		2/177 (1.1%)		1/174 (0.6%)
Pyrexia	2/76 (2.6%)		6/78 (7.7%)		5/177 (2.8%)		1/174 (0.6%)
Infections and infestations
Bronchitis	11/76 (14.5%)		15/78 (19.2%)		11/177 (6.2%)		17/174 (9.8%)
Influenza	4/76 (5.3%)		5/78 (6.4%)		10/177 (5.6%)		3/174 (1.7%)
Lower respiratory tract infection	5/76 (6.6%)		11/78 (14.1%)		13/177 (7.3%)		10/174 (5.7%)
Nasopharyngitis	19/76 (25%)		17/78 (21.8%)		25/177 (14.1%)		31/174 (17.8%)
Pneumonia	3/76 (3.9%)		1/78 (1.3%)		9/177 (5.1%)		3/174 (1.7%)
Respiratory tract infection	5/76 (6.6%)		4/78 (5.1%)		9/177 (5.1%)		8/174 (4.6%)
Rhinitis	4/76 (5.3%)		4/78 (5.1%)		7/177 (4%)		2/174 (1.1%)
Sinusitis	5/76 (6.6%)		6/78 (7.7%)		9/177 (5.1%)		11/174 (6.3%)
Upper respiratory tract infection	13/76 (17.1%)		18/78 (23.1%)		38/177 (21.5%)		31/174 (17.8%)
Urinary tract infection	5/76 (6.6%)		9/78 (11.5%)		11/177 (6.2%)		6/174 (3.4%)
Injury, poisoning and procedural complications
Fall	6/76 (7.9%)		4/78 (5.1%)		3/177 (1.7%)		6/174 (3.4%)
Investigations
Forced vital capacity decreased	4/76 (5.3%)		11/78 (14.1%)		6/177 (3.4%)		6/174 (3.4%)
Weight decreased	5/76 (6.6%)		2/78 (2.6%)		9/177 (5.1%)		11/174 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	5/76 (6.6%)		9/78 (11.5%)		22/177 (12.4%)		17/174 (9.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/76 (11.8%)		9/78 (11.5%)		8/177 (4.5%)		10/174 (5.7%)
Back pain	9/76 (11.8%)		12/78 (15.4%)		11/177 (6.2%)		11/174 (6.3%)
Muscle spasms	5/76 (6.6%)		6/78 (7.7%)		4/177 (2.3%)		2/174 (1.1%)
Musculoskeletal chest pain	1/76 (1.3%)		5/78 (6.4%)		2/177 (1.1%)		1/174 (0.6%)
Musculoskeletal pain	10/76 (13.2%)		5/78 (6.4%)		8/177 (4.5%)		2/174 (1.1%)
Nervous system disorders
Dizziness	10/76 (13.2%)		14/78 (17.9%)		14/177 (7.9%)		11/174 (6.3%)
Headache	9/76 (11.8%)		10/78 (12.8%)		17/177 (9.6%)		11/174 (6.3%)
Psychiatric disorders
Anxiety	5/76 (6.6%)		3/78 (3.8%)		1/177 (0.6%)		2/174 (1.1%)
Insomnia	3/76 (3.9%)		7/78 (9%)		4/177 (2.3%)		8/174 (4.6%)
Respiratory, thoracic and mediastinal disorders
Cough	19/76 (25%)		21/78 (26.9%)		46/177 (26%)		33/174 (19%)
Dysphonia	0/76 (0%)		4/78 (5.1%)		1/177 (0.6%)		0/174 (0%)
Dyspnoea	12/76 (15.8%)		14/78 (17.9%)		18/177 (10.2%)		13/174 (7.5%)
Dyspnoea exertional	4/76 (5.3%)		6/78 (7.7%)		4/177 (2.3%)		5/174 (2.9%)
Idiopathic pulmonary fibrosis	13/76 (17.1%)		11/78 (14.1%)		10/177 (5.6%)		9/174 (5.2%)
Oropharyngeal pain	7/76 (9.2%)		4/78 (5.1%)		5/177 (2.8%)		2/174 (1.1%)
Productive cough	3/76 (3.9%)		8/78 (10.3%)		8/177 (4.5%)		6/174 (3.4%)
Sinus congestion	1/76 (1.3%)		5/78 (6.4%)		1/177 (0.6%)		2/174 (1.1%)
Skin and subcutaneous tissue disorders
Photosensitivity reaction	6/76 (7.9%)		3/78 (3.8%)		24/177 (13.6%)		7/174 (4%)
Pruritus	2/76 (2.6%)		3/78 (3.8%)		12/177 (6.8%)		8/174 (4.6%)
Rash	5/76 (6.6%)		9/78 (11.5%)		21/177 (11.9%)		18/174 (10.3%)
Vascular disorders
Hypertension	4/76 (5.3%)		4/78 (5.1%)		4/177 (2.3%)		7/174 (4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.