Clinical trial NCT03573505: An Efficacy and Safety Study of BG00011 in Participants With Idiopathic Pulmonary Fibrosis
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BG00011 in Patients With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2018-06-29
Enrollment: 109
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Forced (Expiratory) Vital Capacity (FVC) at Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Change From Baseline in FVC, Expressed in Percent Predicted at Week 52
timeFrame: Baseline, Week 52
measure: Time to Progression
timeFrame: Up to Week 60 (End of Study)
measure: Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Number of Participants With at Least One Acute IPF Exacerbation
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Number of IPF Exacerbations
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Number of Participants With Absolute Decline of 10% Predicted in FVC
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Time to Death or Lung Transplantation
timeFrame: Up to Week 60 (End of Study)
measure: Time to All Non-elective Hospitalizations
timeFrame: Up to Week 60 (End of Study)
measure: Time to All Non-Elective Respiratory Hospitalizations
timeFrame: Up to Week 60 (End of Study)
measure: Change From Baseline in Absolute FVC
timeFrame: Up to Week 44
measure: Change From Baseline in Percent Predicted FVC
timeFrame: Up to Week 44
measure: Change From Baseline in Absolute Carbon Monoxide Diffusion Capacity (DLco)
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Change From Baseline in Percent Predicted Carbon Monoxide Diffusion Capacity (DLco)
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Change From Baseline in Absolute Total Lung Capacity (TLC)
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Change From Baseline in Percent Predicted TLC
timeFrame: Up to Early Termination Visit (Up to Week 52)
measure: Change From Baseline in 6 Minute Walk Test (6MWT) Parameters
timeFrame: Baseline, Week 26 and Week 52
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 60 (End of Study)
measure: Number of Participants With Anti-BG00011 Antibodies in the Serum
timeFrame: Up to Week 60 (End of Study)
measure: Concentration of BG00011 in the Serum
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Miami
country: United States
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state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Iowa City
country: United States
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state: Iowa
city: Boston
country: United States
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state: Massachusetts
city: Boston
country: United States
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state: Massachusetts
city: Minneapolis
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state: Minnesota
city: Rochester
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state: Minnesota
city: Chesterfield
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state: Missouri
city: Kansas City
country: United States
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state: Missouri
city: Lebanon
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state: New Hampshire
city: New York
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state: New York
city: Cleveland
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state: Ohio
city: Pittsburgh
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state: Pennsylvania
city: Providence
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state: Rhode Island
city: Charleston
country: United States
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state: South Carolina
city: Nashville
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state: Tennessee
city: Houston
country: United States
facility: Reserach Site
state: Texas
city: Falls Church
country: United States
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state: Virginia
city: Seattle
country: United States
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state: Washington
city: Tacoma
country: United States
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state: Washington
city: Madison
country: United States
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state: Wisconsin
city: Mar del Plata
country: Argentina
facility: Research Site
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
state: Tucuman
city: Darlinghurst
country: Australia
facility: Research Site
state: New South Wales
city: New Lambton Heights
country: Australia
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state: New South Wales
city: Newtown
country: Australia
facility: Research Site
state: New South Wales
city: Chermside
country: Australia
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state: Queensland
city: Nundah
country: Australia
facility: Research Site
state: Queensland
city: Woolloongabba
country: Australia
facility: Research Site
state: Queensland
city: Frankston
country: Australia
facility: Research Site
state: Victoria
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Murdoch
country: Australia
facility: Research Site
state: Western Australia
city: Heidelberg
country: Australia
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Site
city: Talca
country: Chile
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Plzen Bory
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
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city: Praha 8
country: Czechia
facility: Research Site
city: Aarhus C
country: Denmark
facility: Research Site
city: Hellerup
country: Denmark
facility: Research Site
city: Montpellier cedex 5
country: France
facility: Research Site
state: Herault
city: Rennes Cedex 09
country: France
facility: Research Site
state: Ille Et Vilaine
city: Paris Cedex 18
country: France
facility: Research Site
state: Paris
city: Bron cedex
country: France
facility: Research Site
state: Rhone
city: Bobigny Cedex
country: France
facility: Research Site
state: Seine Saint Denis
city: Heraklion
country: Greece
facility: Research Site
city: Larissa
country: Greece
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar-Saba
country: Israel
facility: Research Site
city: Petach Tikva
country: Israel
facility: Research Site
city: Forli
country: Italy
facility: Research Site
state: Cesena
city: Catania
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Nieuwegein
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
state: Barcelona
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
state: Cambridgeshire
city: Exeter
country: United Kingdom
facility: Research Site
state: Devon
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: Edinburgh
country: United Kingdom
facility: Research Site
state: Lothian Region
city: Liverpool
country: United Kingdom
facility: Research Site
state: Merseyside
city: Newcastle
country: United Kingdom
facility: Research Site
state: Tyne & Wear
city: Leeds
country: United Kingdom
facility: Research Site
state: West Yorkshire
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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):e143226. doi: 10.1172/JCI143226.