Idiopathic Pulmonary FibrosisPhase 2NCT01872689
A Study of Lebrikizumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
A Phase 2 study testing Lebrikizumab and Pirfenidone in people with Idiopathic Pulmonary Fibrosis, run by Hoffmann-La Roche at 112 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- Lebrikizumab and Pirfenidone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 505 participants
- Where
- 112 sitesin 13 countries
- Study dates
- 13 Oct 2013to 6 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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)
Trial locations and contacts
112 sites in 13 countries.
112 sites in 13 countries
United States54 sites
Lovelace Scientific Resources, Inc.
Albuquerque, New Mexico, 87108
Piedmont Healthcare Pulmonary and Critical Care Research
Austell, Georgia, 30106
University of Maryland Medical Center
Baltimore, Maryland, 21201
Johns Hopkins Bayview Medical Center - Johns Hopkins Asthma & Allergy Center
Baltimore, Maryland, 21224
University Alabama At Birmingham
Birmingham, Alabama, 35294
Tufts Medical Center
Boston, Massachusetts, 02111
Medical University of South Carolina
Charleston, South Carolina, 29425
Cardiopulmonary Associates LLC Cardiopulmonary Research
Chesterfield, Missouri, 63017
University of Chicago; Pulmonary and Critical Care
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45203-0542
Research Alliance Inc
Clearwater, Florida, 33756
Case Western Research University; University Hospitals Case Medical Center
Cleveland, Ohio, 44106-5067
University Vermont College Medicine Fletcher Allen Health Care
Colchester, Vermont, 05446
Ohio State University
Columbus, Ohio, 43210
Southeastern Lung Care
Decatur, Georgia, 30033
National Jewish Health
Denver, Colorado, 80206
Inova Transplant Center Fairfax Hospital
Falls Church, Virginia, 22042
Penn State University College Medical Allergy And Care Med
Hershey, Pennsylvania, 17033
Baylor College Med
Houston, Texas, 77030
Houston Methodist Hospital
Houston, Texas, 77030
Univ of Iowa Hosp & Clinics; Pulmonary
Iowa City, Iowa, 52242
Mayo Clinic-Jacksonville
Jacksonville, Florida, 32224
Uni of Kansas Medical Center
Kansas City, Kansas, 66160
UCSD Medical Center
La Jolla, California, 92093
University Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792
Loyola University Med Center
Maywood, Illinois, 60153
University Miami
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota Hospital & Clinic
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale New Haven Hospital
New Haven, Connecticut, 06520
Weill Medical College of Cornell University
New York, New York, 10021-5663
Mt Sinai School Medical Pulmo And Critical Care Med
New York, New York, 10029
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, 73104
University of Nebraska
Omaha, Nebraska, 68198-5300
Central Florida Pulmonary Group, PA
Orlando, Florida, 32803
Temple Lung Center, Temple Universtiy-Of the Commomwealth System of Higher Education
Philadelphia, Pennsylvania, 19140
University of Pittsburgh Med Cen; Dorothy P And Richard P Simmons Cen For Interstitial Lung Disease
Pittsburgh, Pennsylvania, 15213
Maine Medical Center -Division of Pulmomary and Critical Care Medicine
Portland, Maine, 04106
The Oregon Clinic.
Portland, Oregon, 97220
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic Rochester
Rochester, Minnesota, 55902
Highland Hospital-University of Rochester Medical Center
Rochester, New York, 14620
University of Utah Health Sciences Center, Lung Health Research Center
Salt Lake City, Utah, 84108
Audie Murphy Va Hospital
San Antonio, Texas, 78229
University of California, San Francisco
San Francisco, California, 94116
Mayo Clinic- Scottsdale
Scottsdale, Arizona, 85259
Pulmonary Consultants
Tacoma, Washington, 98405
USF Tampa General Hospital
Tampa, Florida, 33606
Southern Arizona Veterans Administration Healthcare Systems
Tucson, Arizona, 85723
University of Arizona
Tucson, Arizona, 85724-5030
Cleveland Clinic Florida
Weston, Florida, 33331
Rocky Mountain Center For Clinical Research
Wheat Ridge, Colorado, 80033
Via Christi Hospital Inc. DBA Via Christi Research; Research Dept.
Wichita, Kansas, 67208
United Kingdom7 sites
Southmead Hospital; Respiratory Department
Bristol, BS10-5NB
Papworth Hospital NHS Foundation Trust; Respiratory Department
Cambridge, CB23 3RE
Southampton General Hospital; Respiratory Department
Hampshire, SO16 6YD
St James University Hospital; Respiratory Department
Leeds, LS9 7TF
Respiratory research department clinical science building
Liverpool, L9 7AL
Royal Brompton Hospital; Respiratory Department
London, SW3 6NP
North Manchester Hospital; Respiratory Department
Manchester, M8 5RB
Germany6 sites
Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie
Essen, 45239
Universitätsklinikum Standort Gießen Medizinische Klinik II u. Poliklinik Innere Med./Pneumologie
Giessen, 35392
LungenClinic Großhansdorf
Großhansdorf, 22927
Thoraxklinik Heidelberg gGmbH
Heidelberg, 69126
Fachklinik für Lungenerkrankungen
Immenhausen, 34376
CPC Comprehensive Pneumology Center / Forschungsambulanz, Helmholtz Zentrum
München, 81377
Italy6 sites
A.O.U. Policlinico Vittorio Emanuele; Centro per la cura delle Malattie Rare del Polmone
Catania, Sicily, 95123
Ospedale Morgagni-Pierantoni; U.O. Pneumologia
Forlì, Emilia-Romagna, 47121
Ospedale San Giuseppe; U.O. di Pneumologia
Milan, Lombardy, 20123
A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone
Orbassano (TO), Piedmont, 10043
Policlinico Tor Vergata; UO Mal. Respiratorie; Centro Malattie rare polmone
Rome, Lazio, 00133
A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare
Siena, Tuscany, 53100
Australia5 sites
Box Hill Hospital; Eastern Clinical Research Unit
Box Hill, Victoria, 3128
Royal Prince Alfred Hospital; Department of Respiratory Medicine
Camperdown, New South Wales, 2050
ST VINCENT'S HOSPITAL; Thoracic Medicine
Darlinghurst, New South Wales, 2010
Alfred Hospital; Allergy Immuno Resp
Melbourne, Victoria, 3004
Institute for Respiratory Health Inc
Nedlands, Western Australia, 6009
Canada5 sites
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N4A6
Lawson Health Research Institute a joint venture of LHSC Research Inc and Lawson Research Institute
London, Ontario, N6C 2R5
Dr. Georges-L. Dumont Regional Hospital
Moncton, New Brunswick, E1G 2K5
Institut universitaire de cardiologie et de pneumologie de Québec (Hôpital Laval)
Ste. Foy, Quebec, G1V 4G5
University of British Columbia - Vancouver Coastal Health Authority
Vancouver, British Columbia, V5Z 1M9
France5 sites
Hopital Avicenne; Pneumologie
Bobigny, 93000
Hopital Louis Pradel; Pneumologie
Bron, 69677
Hopital Calmette; Pneumologie
Lille, 59037
Hopital Bichat Claude Bernard ; Service de Pneumologie
Paris, 75877
Hopital de Pontchaillou; Service de Pneumologie
Rennes, 35033
Poland5 sites
Uniwersytecki Szpital Kliniczny Nr 1 im.N.Barlickiego Oddzial Kliniczny Pneumonologii i Alergologii
Lodz, 90-153
Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej
Lublin, 20-064
Klinika Pulmonologii, Alergologii i Onkologii Pulmonologicznej Uniwersytet Medyczny w Poznaniu
Poznan, 60-569
Instytut Gruzlicy i Chorob Płuc
Warsaw, 01-138
Klinika Chorob Pluc i Gruzlicy w Zabrzu; Slaski Uniwersytet Medyczny
Zabrze, 41-803
Spain5 sites
Hospital Universitari de Bellvitge ; Servicio de Neumologia
L'Hospitalet de Llobregat, Barcelona, 08097
Hospital Universitario La Princesa; Servicio de Neumologia
Madrid, 28006
Hospital Clínico San Carlos - Servicio de Neumologia
Madrid, 28040
Hospital Universitario Virgen del Rocio; Servicio de Neumologia
Seville, 41013
Hospital General Universitario De Valencia; Servicio de Neumologia
Valencia, 46014
Belgium4 sites
Hospital Erasme; Neurologie
Brussels, 1070
Cliniques Universitaires St-Luc
Brussels, 1200
UZ Leuven Gasthuisberg
Leuven, 3000
CHU UCL Mont-Godinne
Mont-godinne, 5530
Mexico4 sites
Hospital General Del Estado De Sonora "Dr. Ernesto Ramos Bours"; Servicio De Neumologia
Hermosillo, 83000
Instituto Nacional De Enfermedades Respiratorias;Unidad de Investigación
Mexico City, 14080
Universidad Autonoma De Nuevo Leon, Hospital Universitario Doctor Jose Eleuterio Gonzalez
Monterrey, 64460
Unidad de Investigacion Clinica En Medicina (Udicem) S.C.
Monterrey, 64718
Japan3 sites
Kanagawa Cardiovascular and Respiratory Center; Respiratory Medicine
Kanagawa, 236-0051
Kinki-Chuo Chest Medical Center
Osaka, 591-8555
Tosei General Hospital
Seto-shi, 489-8642
Peru3 sites
Clinica San Pablo
Lima, Lima 33
Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
Lima, Lima 41
Clinica San Borja; NEUMOCARE
Lima, Lima 41
About this study
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
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
- Being tested
- Lebrikizumab, Pirfenidone, Placebo
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LebrikizumabDrug
Also called RO5490255
Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks.
PirfenidoneDrug
Pirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD.
PlaceboDrug
Placebo matched to lebrikizumab will be administered via SC injection once every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Placebo comparator | 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. Receives: Drug: Lebrikizumab; Drug: Placebo |
| Monotherapy (Cohort A): Lebrikizumab | Experimental | 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. Receives: Drug: Lebrikizumab |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Placebo comparator | 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. Receives: Drug: Pirfenidone; Drug: Placebo |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Experimental | 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. Receives: Drug: Lebrikizumab; Drug: Pirfenidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Secondary outcomes (20)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Baseline up to the event of acute IPF exacerbation (up to Week 122)
Percentage of Participants With Respiratory-Related Hospitalization
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Predose (Hour 0) at Week 52
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab
Participants who received lebrikizumab were only included in the analysis.
Measured: 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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2013 (estimated)
- Study start13 Oct 2013
- Primary completion28 Jul 2017
- Study completion6 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 505 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01872689
- Sponsor's protocol ID
- GB28547
- Other IDs
- 2013-001163-24
- Status last verified
- Aug 2018
- First submitted
- 5 Jun 2013
- Last updated
- 24 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 35688625
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01872689
- Acronym / sponsor ID
- GB28547
- Conditions
- Idiopathic Pulmonary Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 505 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 13 Oct 2013 (actual)
- Primary completion
- 28 Jul 2017 (actual)
- Study completion
- 6 Nov 2017 (actual)
- First posted
- 7 Jun 2013 (estimated)
- Results
- Posted 24 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Monotherapy (Cohort A): Placebo | Placebo comparator | Drug: Lebrikizumab, Drug: PlaceboParticipants 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. |
| Monotherapy (Cohort A): Lebrikizumab | Experimental | Drug: LebrikizumabParticipants 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. |
| Combination Therapy (Cohort B): Placebo + Pirfenidone | Placebo comparator | Drug: Pirfenidone, Drug: PlaceboParticipants 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. |
| Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone | Experimental | Drug: Lebrikizumab, Drug: PirfenidoneParticipants 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. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LebrikizumabAlso: RO5490255Lebrikizumab will be administered at a dose of 250 mg via SC injection once every 4 weeks. | Drug | Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone, Monotherapy (Cohort A): Lebrikizumab, Monotherapy (Cohort A): Placebo |
| PirfenidonePirfenidone will be administered orally at a stable dose of 2403 mg per day or at MTD. | Drug | Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone, Combination Therapy (Cohort B): Placebo + Pirfenidone |
| PlaceboPlacebo matched to lebrikizumab will be administered via SC injection once every 4 weeks. | Drug | Combination Therapy (Cohort B): Placebo + Pirfenidone, Monotherapy (Cohort A): Placebo |
Primary outcome
Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks
Time frame: 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.
20 secondary outcomes
Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks
Time frame: 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
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)
Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause
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)
Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks
Time frame: 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
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)
Progression-Free Survival (PFS)
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)
Annualized Rate of Decrease in FVC Over 52 Weeks
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline up to the event of acute IPF exacerbation (up to Week 122)
Time to First Event of Acute IPF Exacerbation
Time frame: Baseline up to the event of acute IPF exacerbation (up to Week 122)
Percentage of Participants With Respiratory-Related Hospitalization
Time frame: Baseline up to the event of respiratory-related hospitalization (up to Week 122)
Time to Respiratory-Related Hospitalization
Time frame: 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
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)
Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause
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)
Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab
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)
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52
Time frame: Predose (Hour 0) at Week 52
Minimum Observed Serum Concentration (Cmin) of Lebrikizumab
Time frame: Predose (Hour 0) at Weeks 4, 12, 24, and 36
Elimination Half-Life (t1/2) of Lebrikizumab
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35688625Allen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
112 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lebrikizumab and Pirfenidone in people with Idiopathic Pulmonary Fibrosis, run by Hoffmann-La Roche at 112 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 112 sites in United States, United Kingdom, Germany, Italy, Australia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks (time frame: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01872689, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2018.