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

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Idiopathic Pulmonary Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Lebrikizumab; Drug: Placebo; Drug: Pirfenidone

• Study Type: Interventional
• Enrollment (Actual): 505
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / 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: Placebo; Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.; Drug: Pirfenidone; Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks	Annualized rates of decrease (slope throughout time from baseline to Week 52) for percent predicted FVC was assessed and reported. FVC is a standard pulmonary function test. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100.	Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks	Annualized rates of decline (slope throughout time from baseline to Week 52) in 6MWT was assessed and reported. 6MWT was the distance (in meters [m]) that a participant could walk in 6 minutes.	Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause	FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100.	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)
Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause	FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100. Time from randomization to first occurrence of an event of >/=10% absolute decline in percent predicted FVC or death from any cause was reported. Participants without an event were censored at the last assessment during the double-blind treatment period. Any participant who underwent lung transplantation was censored at the date of the transplant. The median time to event was estimated using Kaplan-Meier method. 95% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.	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)
Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks	Annualized rates of decrease (slope throughout time from baseline to Week 52) in DLco was assessed and reported. DLco (in milliliters per minute/millimeters of mercury [mL/min/mmHg]) is a measure of the gas transfer.	Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC	FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC = [(observed FVC)/(predicted FVC)]*100.	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)
Progression-Free Survival (PFS)	FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC = [(observed FVC)/(predicted FVC)]*100. PFS was defined as time from randomization to death from any cause, all cause hospitalization, or a decrease from baseline of >/=10% in FVC, whichever occurred first. Participants without an event were censored at the last assessment during the double-blind treatment period. Any participant who underwent lung transplantation was censored at the date of the transplant. The median PFS was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.	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)
Annualized Rate of Decrease in FVC Over 52 Weeks	Annualized rates of decrease (slope throughout time from baseline to Week 52) in FVC (in milliliters per year [mL/year]) was assessed and reported. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position.	Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks	The ATAQ-IPF Version 3 was utilized that included 31 items within 5 domains: cough (6 items), dyspnea (7 items), exhaustion (6 items), emotional well-being (6 items), and independence (6 items). Each item was assessed on a scale ranging from 1 (Strongly disagree) to 4 (Strongly agree). The ATAQ-IPF had a recall specification of 2 weeks. Simple summation scoring was used to derive individual domain scores as well as a total score. ATAQ-IPF total score ranged from 31 to 124 with lower score indicating better quality of life (QoL). Annualized rates of decrease (slope throughout time from baseline to Week 52) in ATAQ-IPF questionnaire total score was assessed and reported.	Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause	The SGRQ is a 50-item health-related QoL instrument that measured health impairment. The questionnaire contains 3 domains: symptoms, activity, and impacts. Items were assessed on various response scales, including a 5-point Likert scale and True/False scale. The SGRQ had a recall specification of 4 weeks. The SGRQ total score (summed weights) ranged from 0 to 100 with a lower score denoting a better health status. Percentage of participants with an event of SGRQ total score worsening (defined as reaching minimal important difference [MID], that is, an increase in total score of >/=7) or death from any cause was reported.	Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause	The SGRQ is a 50-item health-related QoL instrument that measured health impairment. The questionnaire contains 3 domains: symptoms, activity, and impacts. Items were assessed on various response scales, including a 5-point Likert scale and True/False scale. The SGRQ had a recall specification of 4 weeks. The SGRQ total score (summed weights) ranged from 0 to 100 with a lower score denoting a better health status. Time from randomization to first occurrence of an event of SGRQ total score worsening (defined as reaching minimal important difference [MID], that is, an increase in total score of >/=7) or death from any cause was reported. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.	Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation	IPF exacerbation was defined as an event that met all of the following criteria as determined by the investigator: Unexplained worsening or development of dyspnea within the previous 30 days; And radiologic evidence of new bilateral ground-glass abnormality or consolidation, superimposed on a reticular or honeycomb background pattern, that is consistent with usual interstitial pneumonitis; And absence of alternative causes, such as left heart failure, pulmonary embolism, pulmonary infection (on the basis of endotracheal aspirate or bronchoalveolar lavage if available, or investigator judgment), or other events leading to acute lung injury (for example, sepsis, aspiration, trauma, reperfusion pulmonary edema).	Baseline up to the event of acute IPF exacerbation (up to Week 122)
Time to First Event of Acute IPF Exacerbation	Time from randomization to first occurrence of an event of IPF exacerbation was reported. IPF exacerbation was defined as an event that met all of the following criteria as determined by the investigator: Unexplained worsening or development of dyspnea within the previous 30 days; And radiologic evidence of new bilateral ground-glass abnormality or consolidation, superimposed on a reticular or honeycomb background pattern, that is consistent with usual interstitial pneumonitis; And absence of alternative causes, or other events leading to acute lung injury. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.	Baseline up to the event of acute IPF exacerbation (up to Week 122)
Percentage of Participants With Respiratory-Related Hospitalization		Baseline up to the event of respiratory-related hospitalization (up to Week 122)
Time to Respiratory-Related Hospitalization	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.	Baseline up to the event of respiratory-related hospitalization (up to Week 122)
Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause	DLco (in mL/min/mmHg) is a measure of the gas transfer. Predicted DLco is based on sex, age, and height of a person. Percent of predicted DLco (in %) = [(observed DLco)/(predicted DLco)]*100.	Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause	DLco is a measure of the gas transfer. Predicted DLco is based on sex, age, and height of a person. Percent of predicted DLco (in %) = [(observed DLco)/(predicted DLco)]*100. Time from randomization to first occurrence of >/=15% absolute decrease in percentage of predicted DLco or death from any cause was reported. The median time to event was estimated using Kaplan-Meier method. 95% CI for median was computed using the method of Brookmeyer and Crowley.	Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab	ATA to lebrikizumab was tested using a validated immunoassay. A positive ATA result was defined as one in which the presence of detectable ATAs could be confirmed by competitive binding with lebrikizumab. Percentage of participants with positive results for ATA at Baseline and at post-baseline time points were reported. Only participants who received lebrikizumab were included in the analysis.	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)
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52	Participants who received lebrikizumab were only included in the analysis.	Predose (Hour 0) at Week 52
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab	Participants who received lebrikizumab were only included in the analysis.	Predose (Hour 0) at Weeks 4, 12, 24, and 36
Elimination Half-Life (t1/2) of Lebrikizumab	Elimination half-life is the time measured for the plasma drug concentration to decrease by one-half during the elimination phase of the drug. Analysis was performed on PK-Evaluable Population. Participants who received lebrikizumab were only included in the analysis.	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Allen RJ, Stockwell A, Oldham JM, Guillen-Guio B, Schwartz DA, Maher TM, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV; International IPF Genetics Consortium. Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis. Thorax. 2022 Aug;77(8):829-833. doi: 10.1136/thoraxjnl-2021-218577. Epub 2022 Jun 10.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 13, 2013
• Primary Completion (ACTUAL): July 28, 2017
• Study Completion (ACTUAL): November 6, 2017

Study Registration Dates

• First Submitted: June 5, 2013
• First Submitted That Met QC Criteria: June 5, 2013
• First Posted (ESTIMATE): June 7, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: GB28547; 2013-001163-24 (EUDRACT_NUMBER)