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

Study Overview
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Brief Summary
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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.

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

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: BG00011
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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) |