Clinical trial NCT01872689: A Study of Lebrikizumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-06-07
Enrollment: 505
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks
timeFrame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Secondary outcomes:
measure: Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks
timeFrame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
measure: Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
timeFrame: Baseline up to the event of >/=10% absolute decline in percent predicted FVC or death from any cause, whichever occurred first (up to Week 122)
measure: Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
timeFrame: Baseline up to the event of >/=10% absolute decline in percent predicted FVC or death from any cause, whichever occurred first (up to Week 122)
measure: Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks
timeFrame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
measure: Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC
timeFrame: Baseline up to the event of death from any cause, all cause hospitalization, or a decrease from baseline of >/=10% in FVC, whichever occurred first (up to Week 122)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to the event of death from any cause, all cause hospitalization, or a decrease from baseline of >/=10% in FVC, whichever occurred first (up to Week 122)
measure: Annualized Rate of Decrease in FVC Over 52 Weeks
timeFrame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
measure: Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks
timeFrame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
measure: Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause
timeFrame: Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
measure: Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause
timeFrame: Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122)
measure: Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
timeFrame: Baseline up to the event of acute IPF exacerbation (up to Week 122)
measure: Time to First Event of Acute IPF Exacerbation
timeFrame: Baseline up to the event of acute IPF exacerbation (up to Week 122)
measure: Percentage of Participants With Respiratory-Related Hospitalization
timeFrame: Baseline up to the event of respiratory-related hospitalization (up to Week 122)
measure: Time to Respiratory-Related Hospitalization
timeFrame: Baseline up to the event of respiratory-related hospitalization (up to Week 122)
measure: Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
timeFrame: Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
measure: Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
timeFrame: Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122)
measure: Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab
timeFrame: Baseline and Post-Baseline (assessed at multiple time points: Weeks 4, 12, 24, 36, 52, 56, 64, 76, and at safety follow-up up to Week 122)
measure: Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52
timeFrame: Predose (Hour 0) at Week 52
measure: Minimum Observed Serum Concentration (Cmin) of Lebrikizumab
timeFrame: Predose (Hour 0) at Weeks 4, 12, 24, and 36
measure: Elimination Half-Life (t1/2) of Lebrikizumab
timeFrame: Pre-dose (Hour 0) at Weeks 1, 4, 12, 24, 36, 64, 76, 88, 104; and at 4, 12, and 18 weeks post-last dose (last dose = Week 104)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Alabama At Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic- Scottsdale
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona Veterans Administration Healthcare Systems
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Wheat Ridge
country: United States
facility: Rocky Mountain Center For Clinical Research
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Clearwater
country: United States
facility: Research Alliance Inc
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: University Miami
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Tampa
country: United States
facility: USF Tampa General Hospital
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Austell
country: United States
facility: Piedmont Healthcare Pulmonary and Critical Care Research
state: Georgia
city: Decatur
country: United States
facility: Southeastern Lung Care
state: Georgia
city: Chicago
country: United States
facility: University of Chicago; Pulmonary and Critical Care
state: Illinois
city: Maywood
country: United States
facility: Loyola University Med Center
state: Illinois
city: Iowa City
country: United States
facility: Univ of Iowa Hosp & Clinics; Pulmonary
state: Iowa
city: Kansas
country: United States
facility: Uni of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Via Christi Hospital Inc. DBA Via Christi Research; Research Dept.
state: Kansas
city: Portland
country: United States
facility: Maine Medical Center -Division of Pulmomary and Critical Care Medicine
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center - Johns Hopkins Asthma & Allergy Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Hospital & Clinic
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Chesterfield
country: United States
facility: Cardiopulmonary Associates LLC Cardiopulmonary Research
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources, Inc.
state: New Mexico
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Mt Sinai School Medical Pulmo And Critical Care Med
state: New York
city: Rochester
country: United States
facility: Highland Hospital-University of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Research University; University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: The Oregon Clinic.
state: Oregon
city: Hershey
country: United States
facility: Penn State University College Medical Allergy And Care Med
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Lung Center, Temple Universtiy-Of the Commomwealth System of Higher Education
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Med Cen; Dorothy P And Richard P Simmons Cen For Interstitial Lung Disease
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College Med
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Audie Murphy Va Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center, Lung Health Research Center
state: Utah
city: Colchester
country: United States
facility: University Vermont College Medicine Fletcher Allen Health Care
state: Vermont
city: Falls Church
country: United States
facility: Inova Transplant Center Fairfax Hospital
state: Virginia
city: Tacoma
country: United States
facility: Pulmonary Consultants
state: Washington
city: Madison
country: United States
facility: University Wisconsin Hospitals and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital; Department of Respiratory Medicine
state: New South Wales
city: Darlinghurst
country: Australia
facility: ST VINCENT'S HOSPITAL; Thoracic Medicine
state: New South Wales
city: Box Hill
country: Australia
facility: Box Hill Hospital; Eastern Clinical Research Unit
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital; Allergy Immuno Resp
state: Victoria
city: Nedlands
country: Australia
facility: Institute for Respiratory Health Inc
state: Western Australia
city: Bruxelles
country: Belgium
facility: Hospital Erasme; Neurologie
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Mont-godinne
country: Belgium
facility: CHU UCL Mont-Godinne
city: Vancouver
country: Canada
facility: University of British Columbia - Vancouver Coastal Health Authority
state: British Columbia
city: Moncton
country: Canada
facility: Dr. Georges-L. Dumont Regional Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: London
country: Canada
facility: Lawson Health Research Institute a joint venture of LHSC Research Inc and Lawson Research Institute
state: Ontario
city: Ste. Foy
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec (Hôpital Laval)
state: Quebec
city: Bobigny
country: France
facility: Hopital Avicenne; Pneumologie
city: Bron
country: France
facility: Hopital Louis Pradel; Pneumologie
city: Lille
country: France
facility: Hopital Calmette; Pneumologie
city: Paris
country: France
facility: Hopital Bichat Claude Bernard ; Service de Pneumologie
city: Rennes
country: France
facility: Hopital de Pontchaillou; Service de Pneumologie
city: Essen
country: Germany
facility: Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie
city: Gießen
country: Germany
facility: Universitätsklinikum Standort Gießen Medizinische Klinik II u. Poliklinik Innere Med./Pneumologie
city: Großhansdorf
country: Germany
facility: LungenClinic Großhansdorf
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: München
country: Germany
facility: CPC Comprehensive Pneumology Center / Forschungsambulanz, Helmholtz Zentrum
city: Forlì
country: Italy
facility: Ospedale Morgagni-Pierantoni; U.O. Pneumologia
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Tor Vergata; UO Mal. Respiratorie; Centro Malattie rare polmone
state: Lazio
city: Milano
country: Italy
facility: Ospedale San Giuseppe; U.O. di Pneumologia
state: Lombardia
city: Orbassano (TO)
country: Italy
facility: A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone
state: Piemonte
city: Catania
country: Italy
facility: A.O.U. Policlinico Vittorio Emanuele; Centro per la cura delle Malattie Rare del Polmone
state: Sicilia
city: Siena
country: Italy
facility: A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare
state: Toscana
city: Kanagawa
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center; Respiratory Medicine
city: Osaka
country: Japan
facility: Kinki-Chuo Chest Medical Center
city: Seto-shi
country: Japan
facility: Tosei General Hospital
city: Hermosillo
country: Mexico
facility: Hospital General Del Estado De Sonora "Dr. Ernesto Ramos Bours"; Servicio De Neumologia
city: Mexico City
country: Mexico
facility: Instituto Nacional De Enfermedades Respiratorias;Unidad de Investigación
city: Monterrey
country: Mexico
facility: Universidad Autonoma De Nuevo Leon, Hospital Universitario Doctor Jose Eleuterio Gonzalez
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica En Medicina (Udicem) S.C.
city: Lima
country: Peru
facility: Clinica San Pablo
city: Lima
country: Peru
facility: Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
city: Lima
country: Peru
facility: Clinica San Borja; NEUMOCARE
city: Lodz
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr 1 im.N.Barlickiego Oddzial Kliniczny Pneumonologii i Alergologii
city: Lublin
country: Poland
facility: Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej
city: Poznan
country: Poland
facility: Klinika Pulmonologii, Alergologii i Onkologii Pulmonologicznej Uniwersytet Medyczny w Poznaniu
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorob Płuc
city: Zabrze
country: Poland
facility: Klinika Chorob Pluc i Gruzlicy w Zabrzu; Slaski Uniwersytet Medyczny
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge ; Servicio de Neumologia
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa; Servicio de Neumologia
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos - Servicio de Neumologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Neumologia
city: Valencia
country: Spain
facility: Hospital General Universitario De Valencia; Servicio de Neumologia
city: Bristol
country: United Kingdom
facility: Southmead Hospital; Respiratory Department
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust; Respiratory Department
city: Hampshire
country: United Kingdom
facility: Southampton General Hospital; Respiratory Department
city: Leeds
country: United Kingdom
facility: St James University Hospital; Respiratory Department
city: Liverpool
country: United Kingdom
facility: Respiratory research department clinical science building
city: London
country: United Kingdom
facility: Royal Brompton Hospital; Respiratory Department
city: Manchester
country: United Kingdom
facility: North Manchester Hospital; Respiratory Department
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.