An Efficacy and Safety Study of BG00011 in Participants With Idiopathic Pulmonary Fibrosis (SPIRIT)

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BG00011 in Patients With Idiopathic Pulmonary Fibrosis

The primary objective of this study is to evaluate the efficacy of BG00011 compared with placebo in participants with Idiopathic Pulmonary Fibrosis (IPF). The secondary objectives of this study are: to evaluate the efficacy of BG00011 compared with placebo in participants with IPF as determined by change in percent predicted forced (expiratory) vital capacity (FVC); to assess progression-free survival in participants who receive BG00011 compared with placebo; to assess the occurrence of IPF exacerbation in participants who receive BG00011 compared with placebo; to assess the incidence of absolute decline in FVC ≥10% in participants who receive BG00011 compared with placebo; to assess the time to death or lung transplantation in participants who receive BG00011 compared with placebo, and the transplant-free survival rate at Week 26 and Week 52; to assess the time to non-elective hospitalizations in participants who receive BG00011 compared with placebo; to assess additional pulmonary function test (PFT) findings in participants who receive BG00011 compared with placebo; To assess performance on the 6 minute walk test (6MWT) in participants who receive BG00011 compared with placebo; to evaluate the safety and tolerability of BG00011; and to evaluate the serum concentration of BG00011.

Study Overview

• Status: Terminated
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: BG00011

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Mar del Plata, Buenos Aires, Argentina, B7600FZ
      • Research Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Research Site
• Australia
  • Heidelberg, Australia, 3084
    • Research Site
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Research Site
    • New Lambton Heights, New South Wales, Australia, 2305
      • Research Site
    • Newtown, New South Wales, Australia, 2042
      • Research Site
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Research Site
    • Nundah, Queensland, Australia, 4012
      • Research Site
    • Woolloongabba, Queensland, Australia, 4102
      • Research Site
  • Victoria
    • Frankston, Victoria, Australia, 3939
      • Research Site
    • Melbourne, Victoria, Australia, 3004
      • Research Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Research Site
• Belgium
  • Bruxelles, Belgium, 1070
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Yvoir, Belgium, 5530
    • Research Site
• Chile
  • Talca, Chile, 3465586
    • Research Site
• Czechia
  • Olomouc, Czechia, 775 20
    • Research Site
  • Plzen Bory, Czechia, 305 99
    • Research Site
  • Praha 4, Czechia, 140 59
    • Research Site
  • Praha 8, Czechia, 180 01
    • Research Site
• Denmark
  • Aarhus C, Denmark, 8000
    • Research Site
  • Hellerup, Denmark, 2900
    • Research Site
• France
  • Herault
    • Montpellier cedex 5, Herault, France, 34295
      • Research Site
  • Ille Et Vilaine
    • Rennes Cedex 09, Ille Et Vilaine, France, 35033
      • Research Site
  • Paris
    • Paris Cedex 18, Paris, France, 75877
      • Research Site
  • Rhone
    • Bron cedex, Rhone, France, 69677
      • Research Site
  • Seine Saint Denis
    • Bobigny Cedex, Seine Saint Denis, France, 93009
      • Research Site
• Greece
  • Heraklion, Greece, 71110
    • Research Site
  • Larissa, Greece, 41110
    • Research Site
• Israel
  • Haifa, Israel, 34362
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Kfar-Saba, Israel, 4428164
    • Research Site
  • Petach Tikva, Israel, 49100
    • Research Site
• Italy
  • Catania, Italy, 95123
    • Research Site
  • Milano, Italy, 20123
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Siena, Italy, 53100
    • Research Site
  • Cesena
    • Forli, Cesena, Italy, 47100
      • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 3080
    • Research Site
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Research Site
  • Nieuwegein, Netherlands, 3435 CM
    • Research Site
  • Rotterdam, Netherlands, 3015 CE
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Warszawa, Poland, 01-138
    • Research Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620039
    • Research Site
  • Kazan, Russian Federation, 420103
    • Research Site
  • Saint-Petersburg, Russian Federation, 197022
    • Research Site
  • Yaroslavl, Russian Federation, 150003
    • Research Site
• Spain
  • Barcelona, Spain, 08025
    • Research Site
  • Barcelona, Spain, 08006
    • Research Site
  • Madrid, Spain, 28006
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Valencia, Spain, 46014
    • Research Site
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Research Site
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0AY
      • Research Site
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Research Site
  • Greater London
    • London, Greater London, United Kingdom, SW3 6NP
      • Research Site
    • London, Greater London, United Kingdom, W12 0HS
      • Research Site
  • Lothian Region
    • Edinburgh, Lothian Region, United Kingdom, EH4 2XU
      • Research Site
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L9 7AL
      • Research Site
  • Tyne & Wear
    • Newcastle, Tyne & Wear, United Kingdom, NE1 4LP
      • Research Site
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Research Site
    • Phoenix, Arizona, United States, 85013
      • Research Site
  • California
    • Los Angeles, California, United States, 90048
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3221
      • Research Site
  • Florida
    • Miami, Florida, United States, 33125
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Research Site
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Research Site
    • Kansas City, Missouri, United States, 66160
      • Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Research Site
  • New York
    • New York, New York, United States, 10029
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Reserach Site
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Research Site
    • Tacoma, Washington, United States, 98405
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Research Site

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

Key Inclusion Criteria:

• Female subjects must be surgically sterile, postmenopausal (minimum 1 year without menses), or agree to use 1 or more forms of highly effective contraception from the time of signing of the informed consent form (ICF) until 3 months after the last injection of study medication. Male subjects must also agree to use 1 or more forms of highly effective contraception for either themselves or their partners from signing of ICF until 4 months after last injection of study medication.
• IPF diagnosed based on modified ATS/ERS/JRS/ALAT IPF guideline for diagnosis and management, within 3 years of Screening.
• Combination of high-resolution computed tomography (HRCT) pattern and, if one has been obtained, surgical lung biopsy pattern, consistent with diagnosis of IPF.
• Carbon monoxide diffusion capacity (DLco) (corrected for hemoglobin): 30% to 79% predicted of normal at Screening, with no clinically significant deterioration between the Screening Visit and randomization, as determined by the Investigator.
• Forced (expiratory) vital capacity (FVC) ≥50% predicted of normal at Screening, with no clinically significant deterioration between the Screening Visit and randomization, as determined by the Investigator.
• If a subject is taking nintedanib or pirfenidone, they must be on a stable dose for at least 8 weeks prior to randomization.

Key Exclusion Criteria:

• Unable to perform pulmonary functional tests (PFTs) or undergo HRCT procedure.
• Peripheral capillary oxygen saturation (SpO2) <90% at rest (if on oxygen supplementation, must be ≤2 L/min at rest).
• Airway obstruction (i.e., prebronchodilator FEV1/FVC <0.7) or evidence of a bronchodilator response as defined by an absolute increase of ≥12% and an increase of ≥200 milliliters (mL) in FEV1 or FVC, or both, after bronchodilator use, compared with the values before bronchodilator use at Screening.
• End-stage fibrotic disease likely requiring organ transplantation within 12 months, or if the subject has initiated active evaluation for organ transplantation.
• The extent of emphysema in the lungs exceeds fibrosis, based on central review of HRCT scans.
• Body weight <60 kg at Screening.
• History of or ongoing malignant disease, including solid tumors and hematologic malignancies, with the exception of basal cell carcinomas, squamous cell carcinomas, and carcinoma in situ of the cervix that have been completely excised and considered cured >2 years prior to Screening.
• Significant cardiac disease (e.g., New York Heart Association Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias; or pulmonary hypertension requiring pharmacologic treatment).
• Clinical diagnosis of any connective tissue disease (including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis) or a diagnosis of interstitial pneumonia with autoimmune features as determined by the Investigator.
• Other disease that may interfere with testing procedures or, in the judgment of the Investigator, may interfere with study participation or may put the patient at risk when participating in this study.
• Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the subject unsuitable for enrollment.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BG00011; Participants will receive BG00011 56 mg once weekly by subcutaneous (SC) injection for 52 weeks.	Drug: BG00011; Administered as specified in the treatment arm.
Placebo Comparator: Placebo; Participants will receive placebo once weekly by (SC) injection for 52 weeks.	Drug: Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced (Expiratory) Vital Capacity (FVC) at Week 52	FVC is the total amount of air exhaled during the forced expiratory volume test that is measured during spirometry and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs. Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in FVC, Expressed in Percent Predicted at Week 52	FVC is the total amount of air exhaled during the forced expiratory volume test that is measured during spirometry and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which is used to dilate participant's bronchial (breathing) tubes. Percent predicted FVC (in %, here FVC was measured in litres) = [(observed FVC)/(predicted FVC)]*100. Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Baseline, Week 52
Time to Progression	Time to progression is defined by a composite endpoint, including any of the following events: Absolute decline of 10% predicted in FVC (FVC percent predicted (baseline) - FVC percent predicted (progression) ≥10%); Non-elective hospitalization for respiratory events; Lung transplantation or death. The earliest time to meet at least 1 composite criterion was calculated.	Up to Week 60 (End of Study)
Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation	Time to first acute IPF exacerbation is defined as time from randomization to the first occurrence of acute IPF exacerbation. Acute IPF exacerbation is defined as a clinically significant deterioration of unidentifiable cause in a participant with underlying IPF. The diagnostic criteria for IPF used in this study were derived from evidence-based guidelines developed by the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) joint task force for the diagnosis and management of IPF. Participants were assessed according to the modified 2007 diagnostic criteria for acute IPF exacerbation.	Up to Early Termination Visit (Up to Week 52)
Number of Participants With at Least One Acute IPF Exacerbation	Acute IPF exacerbation is defined as a clinically significant deterioration of unidentifiable cause in a participant with underlying IPF. The diagnostic criteria for IPF used in this study were derived from evidence-based guidelines developed by the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) joint task force for the diagnosis and management of IPF. Participants were assessed according to the modified 2007 diagnostic criteria for acute IPF exacerbation.	Up to Early Termination Visit (Up to Week 52)
Number of IPF Exacerbations	The IPF exacerbation is defined as a clinically significant deterioration of unidentifiable cause in a participant with underlying IPF. The diagnostic criteria for IPF used in this study were derived from evidence-based guidelines developed by the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) joint task force for the diagnosis and management of IPF. Participants were assessed according to the modified 2007 diagnostic criteria for acute IPF exacerbation.	Up to Early Termination Visit (Up to Week 52)
Number of Participants With Absolute Decline of 10% Predicted in FVC	FVC is the is the total amount of air exhaled during the forced expiratory volume test that is measured during spirometry and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which is used to dilate participant's bronchial (breathing) tubes. Absolute Decline of 10% = FVC percent predicted (baseline) - FVC percent predicted (progression) ≥10%.	Up to Early Termination Visit (Up to Week 52)
Time to Death or Lung Transplantation	Time to Death or Lung Transplantation is defined as the time from randomization to the first occurrence of any one of the event (death or lung transplantation).	Up to Week 60 (End of Study)
Time to All Non-elective Hospitalizations	Time to all non-elective hospitalizations is defined as the time from randomization to the first occurrence of hospitalization which was not elected by the participant.	Up to Week 60 (End of Study)
Time to All Non-Elective Respiratory Hospitalizations	Time to all non-elective respiratory hospitalizations is defined as the time from randomization to the first occurrence of hospitalization due to respiratory problems, which was not elected by the participant.	Up to Week 60 (End of Study)
Change From Baseline in Absolute FVC	FVC is the total amount of air exhaled during the forced expiratory volume test that is measured during spirometry and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which is used to dilate participant's bronchial (breathing) tubes. Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Up to Week 44
Change From Baseline in Percent Predicted FVC	FVC is the total amount of air exhaled during the forced expiratory volume test that is measured during spirometry and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which is used to dilate participant's bronchial (breathing) tubes. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100. Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Up to Week 44
Change From Baseline in Absolute Carbon Monoxide Diffusion Capacity (DLco)	DLCO is a measurement of the ability of the lungs to transfer gases from the air to the blood. Evaluation of DLco was be performed by single-breath carbon monoxide diffusing capacity. DLCO was assessed in milliliters per minute per millimeter of mercury (mL/min/mmHg). Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Up to Early Termination Visit (Up to Week 52)
Change From Baseline in Percent Predicted Carbon Monoxide Diffusion Capacity (DLco)	DLCO is a measurement of the ability of the lungs to transfer gases from the air to the blood. Evaluation of DLco was be performed by single-breath carbon monoxide diffusing capacity. Percent of predicted DLco (in %) = [(observed DLco)/(predicted DLco)]*100. Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Up to Early Termination Visit (Up to Week 52)
Change From Baseline in Absolute Total Lung Capacity (TLC)	Total lung capacity is the measure of lung volume was measured by full-body plethysmography. Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Up to Early Termination Visit (Up to Week 52)
Change From Baseline in Percent Predicted TLC	Total lung capacity is the measure of lung volume was measured by full-body plethysmography. Percent predicted TLC (in %) = [(observed TLC)/(predicted TLC)]*100. Change from baseline is defined as post-baseline value minus baseline value. A negative change from baseline indicates decline.	Up to Early Termination Visit (Up to Week 52)
Change From Baseline in 6 Minute Walk Test (6MWT) Parameters	The 6MWT measures the distance (in meters), a participant is able to walk in 6 minutes. This test measures the distance a person can walk quickly on a flat, hard surface in 6 minutes and reflects an individual's ability to perform daily physical activities.	Baseline, Week 26 and Week 52
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, requires inpatient hospitalization, results in persistent or significant disability and/or results in a congenital anomaly.	Up to Week 60 (End of Study)
Number of Participants With Anti-BG00011 Antibodies in the Serum		Up to Week 60 (End of Study)
Concentration of BG00011 in the Serum		Predose on Day 0, Day 5, Week 4, Week 8, Week 12, Week 26, Week 38, Week 52, and Safety Follow-up Visit (Up to Week 60)

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• Raghu G, Mouded M, Chambers DC, Martinez FJ, Richeldi L, Lancaster LH, Hamblin MJ, Gibson KF, Rosas IO, Prasse A, Zhao G, Serenko M, Novikov N, McCurley A, Bansal P, Stebbins C, Arefayene M, Ibebunjo S, Violette SM, Gallagher D, Behr J. A Phase IIb Randomized Clinical Study of an Anti-alphavbeta6 Monoclonal Antibody in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2022 Nov 1;206(9):1128-1139. doi: 10.1164/rccm.202112-2824OC.
• Shenderov K, Collins SL, Powell JD, Horton MR. Immune dysregulation as a driver of idiopathic pulmonary fibrosis. J Clin Invest. 2021 Jan 19;131(2). pii: 143226. doi: 10.1172/JCI143226. Review.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2018
• Primary Completion (Actual): November 14, 2019
• Study Completion (Actual): November 14, 2019

Study Registration Dates

• First Submitted: June 19, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 29, 2018

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: 203PF203; 2017-003158-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No