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

NCT ID: NCT01872689

Last Updated: 2018-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 505 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-13
• Study Completion Date: 2017-11-06

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.

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Lebrikizumab

Intervention Type: DRUG

Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.

Placebo

Intervention Type: DRUG

Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.

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.

Group Type: EXPERIMENTAL

Lebrikizumab

Intervention Type: DRUG

Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.

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.

Group Type: PLACEBO_COMPARATOR

Pirfenidone

Intervention Type: DRUG

Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.

Placebo

Intervention Type: DRUG

Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.

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.

Group Type: EXPERIMENTAL

Lebrikizumab

Intervention Type: DRUG

Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.

Pirfenidone

Intervention Type: DRUG

Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.

Interventions

Lebrikizumab

Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.

Intervention Type: DRUG

Pirfenidone

Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.

Intervention Type: DRUG

Placebo

Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.

Intervention Type: DRUG

Other Intervention Names

RO5490255

Eligibility Criteria

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)

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University Alabama At Birmingham

Birmingham, Alabama, United States

Mayo Clinic- Scottsdale

Scottsdale, Arizona, United States

Southern Arizona Veterans Administration Healthcare Systems

Tucson, Arizona, United States

University of Arizona

Tucson, Arizona, United States

UCSD Medical Center

La Jolla, California, United States

University of California, San Francisco

San Francisco, California, United States

National Jewish Health

Denver, Colorado, United States

Rocky Mountain Center For Clinical Research

Wheat Ridge, Colorado, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Research Alliance Inc

Clearwater, Florida, United States

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

University Miami

Miami, Florida, United States

Central Florida Pulmonary Group, PA

Orlando, Florida, United States

USF Tampa General Hospital

Tampa, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

Piedmont Healthcare Pulmonary and Critical Care Research

Austell, Georgia, United States

Southeastern Lung Care

Decatur, Georgia, United States

University of Chicago; Pulmonary and Critical Care

Chicago, Illinois, United States

Loyola University Med Center

Maywood, Illinois, United States

Univ of Iowa Hosp & Clinics; Pulmonary

Iowa City, Iowa, United States

Uni of Kansas Medical Center

Kansas City, Kansas, United States

Via Christi Hospital Inc. DBA Via Christi Research; Research Dept.

Wichita, Kansas, United States

Maine Medical Center -Division of Pulmomary and Critical Care Medicine

Portland, Maine, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Johns Hopkins Bayview Medical Center - Johns Hopkins Asthma & Allergy Center

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Minnesota Hospital & Clinic

Minneapolis, Minnesota, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Cardiopulmonary Associates LLC Cardiopulmonary Research

Chesterfield, Missouri, United States

University of Nebraska

Omaha, Nebraska, United States

Lovelace Scientific Resources, Inc.

Albuquerque, New Mexico, United States

Weill Medical College of Cornell University

New York, New York, United States

Mt Sinai School Medical Pulmo And Critical Care Med

New York, New York, United States

Highland Hospital-University of Rochester Medical Center

Rochester, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Case Western Research University; University Hospitals Case Medical Center

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, United States

The Oregon Clinic.

Portland, Oregon, United States

Penn State University College Medical Allergy And Care Med

Hershey, Pennsylvania, United States

Temple Lung Center, Temple Universtiy-Of the Commomwealth System of Higher Education

Philadelphia, Pennsylvania, United States

University of Pittsburgh Med Cen; Dorothy P And Richard P Simmons Cen For Interstitial Lung Disease

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor College Med

Houston, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Audie Murphy Va Hospital

San Antonio, Texas, United States

University of Utah Health Sciences Center, Lung Health Research Center

Salt Lake City, Utah, United States

University Vermont College Medicine Fletcher Allen Health Care

Colchester, Vermont, United States

Inova Transplant Center Fairfax Hospital

Falls Church, Virginia, United States

Pulmonary Consultants

Tacoma, Washington, United States

University Wisconsin Hospitals and Clinics

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Royal Prince Alfred Hospital; Department of Respiratory Medicine

Camperdown, New South Wales, Australia

ST VINCENT'S HOSPITAL; Thoracic Medicine

Darlinghurst, New South Wales, Australia

Box Hill Hospital; Eastern Clinical Research Unit

Box Hill, Victoria, Australia

Alfred Hospital; Allergy Immuno Resp

Melbourne, Victoria, Australia

Institute for Respiratory Health Inc

Nedlands, Western Australia, Australia

Hospital Erasme; Neurologie

Brussels, , Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

CHU UCL Mont-Godinne

Mont-godinne, , Belgium

University of British Columbia - Vancouver Coastal Health Authority

Vancouver, British Columbia, Canada

Dr. Georges-L. Dumont Regional Hospital

Moncton, New Brunswick, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Lawson Health Research Institute a joint venture of LHSC Research Inc and Lawson Research Institute

London, Ontario, Canada

Institut universitaire de cardiologie et de pneumologie de Québec (Hôpital Laval)

Ste. Foy, Quebec, Canada

Hopital Avicenne; Pneumologie

Bobigny, , France

Hopital Louis Pradel; Pneumologie

Bron, , France

Hopital Calmette; Pneumologie

Lille, , France

Hopital Bichat Claude Bernard ; Service de Pneumologie

Paris, , France

Hopital de Pontchaillou; Service de Pneumologie

Rennes, , France

Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie

Essen, , Germany

Universitätsklinikum Standort Gießen Medizinische Klinik II u. Poliklinik Innere Med./Pneumologie

Giessen, , Germany

LungenClinic Großhansdorf

Großhansdorf, , Germany

Thoraxklinik Heidelberg gGmbH

Heidelberg, , Germany

Fachklinik für Lungenerkrankungen

Immenhausen, , Germany

CPC Comprehensive Pneumology Center / Forschungsambulanz, Helmholtz Zentrum

München, , Germany

Ospedale Morgagni-Pierantoni; U.O. Pneumologia

Forlì, Emilia-Romagna, Italy

Policlinico Tor Vergata; UO Mal. Respiratorie; Centro Malattie rare polmone

Rome, Lazio, Italy

Ospedale San Giuseppe; U.O. di Pneumologia

Milan, Lombardy, Italy

A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone

Orbassano (TO), Piedmont, Italy

A.O.U. Policlinico Vittorio Emanuele; Centro per la cura delle Malattie Rare del Polmone

Catania, Sicily, Italy

A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare

Siena, Tuscany, Italy

Kanagawa Cardiovascular and Respiratory Center; Respiratory Medicine

Kanagawa, , Japan

Kinki-Chuo Chest Medical Center

Osaka, , Japan

Tosei General Hospital

Seto-shi, , Japan

Hospital General Del Estado De Sonora "Dr. Ernesto Ramos Bours"; Servicio De Neumologia

Hermosillo, , Mexico

Instituto Nacional De Enfermedades Respiratorias;Unidad de Investigación

Mexico City, , Mexico

Universidad Autonoma De Nuevo Leon, Hospital Universitario Doctor Jose Eleuterio Gonzalez

Monterrey, , Mexico

Unidad de Investigacion Clinica En Medicina (Udicem) S.C.

Monterrey, , Mexico

Clinica San Pablo

Lima, , Peru

Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional

Lima, , Peru

Clinica San Borja; NEUMOCARE

Lima, , Peru

Uniwersytecki Szpital Kliniczny Nr 1 im.N.Barlickiego Oddzial Kliniczny Pneumonologii i Alergologii

Lodz, , Poland

Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej

Lublin, , Poland

Klinika Pulmonologii, Alergologii i Onkologii Pulmonologicznej Uniwersytet Medyczny w Poznaniu

Poznan, , Poland

Instytut Gruzlicy i Chorob Płuc

Warsaw, , Poland

Klinika Chorob Pluc i Gruzlicy w Zabrzu; Slaski Uniwersytet Medyczny

Zabrze, , Poland

Hospital Universitari de Bellvitge ; Servicio de Neumologia

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario La Princesa; Servicio de Neumologia

Madrid, , Spain

Hospital Clínico San Carlos - Servicio de Neumologia

Madrid, , Spain

Hospital Universitario Virgen del Rocio; Servicio de Neumologia

Seville, , Spain

Hospital General Universitario De Valencia; Servicio de Neumologia

Valencia, , Spain

Southmead Hospital; Respiratory Department

Bristol, , United Kingdom

Papworth Hospital NHS Foundation Trust; Respiratory Department

Cambridge, , United Kingdom

Southampton General Hospital; Respiratory Department

Hampshire, , United Kingdom

St James University Hospital; Respiratory Department

Leeds, , United Kingdom

Respiratory research department clinical science building

Liverpool, , United Kingdom

Royal Brompton Hospital; Respiratory Department

London, , United Kingdom

North Manchester Hospital; Respiratory Department

Manchester, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Italy; Japan; Mexico; Peru; Poland; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35688625 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2013-001163-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GB28547

Identifier Type: -

Identifier Source: org_study_id