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

Idiopathic Pulmonary Fibrosis Clinical Trial

— SPIRIT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03573505
• Other study ID #: 203PF203
• Secondary ID: 2017-003158-18
• Status: Terminated
• Phase: Phase 2
• Start date: September 24, 2018
• Est. completion date: November 14, 2019

Study information

• Verified date: December 2020
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 109
• Est. completion date: November 14, 2019
• Est. primary completion date: November 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• BG00011
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Argentina	Research Site	Mar del Plata	Buenos Aires
Argentina	Research Site	San Miguel de Tucuman	Tucuman
Australia	Research Site	Chermside	Queensland
Australia	Research Site	Darlinghurst	New South Wales
Australia	Research Site	Frankston	Victoria
Australia	Research Site	Heidelberg
Australia	Research Site	Melbourne	Victoria
Australia	Research Site	Murdoch	Western Australia
Australia	Research Site	New Lambton Heights	New South Wales
Australia	Research Site	Newtown	New South Wales
Australia	Research Site	Nundah	Queensland
Australia	Research Site	Woolloongabba	Queensland
Belgium	Research Site	Bruxelles
Belgium	Research Site	Leuven
Belgium	Research Site	Yvoir
Chile	Research Site	Talca
Czechia	Research Site	Olomouc
Czechia	Research Site	Plzen Bory
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 8
Denmark	Research Site	Aarhus C
Denmark	Research Site	Hellerup
France	Research Site	Bobigny Cedex	Seine Saint Denis
France	Research Site	Bron cedex	Rhone
France	Research Site	Montpellier cedex 5	Herault
France	Research Site	Paris Cedex 18	Paris
France	Research Site	Rennes Cedex 09	Ille Et Vilaine
Greece	Research Site	Heraklion
Greece	Research Site	Larissa
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar-Saba
Israel	Research Site	Petach Tikva
Italy	Research Site	Catania
Italy	Research Site	Forli	Cesena
Italy	Research Site	Milano
Italy	Research Site	Roma
Italy	Research Site	Siena
Korea, Republic of	Research Site	Seongnam-si	Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Nieuwegein
Netherlands	Research Site	Rotterdam
Poland	Research Site	Gdansk
Poland	Research Site	Warszawa
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Yaroslavl
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
United Kingdom	Research Site	Cambridge	Cambridgeshire
United Kingdom	Research Site	Edinburgh	Lothian Region
United Kingdom	Research Site	Exeter	Devon
United Kingdom	Research Site	Leeds	West Yorkshire
United Kingdom	Research Site	Liverpool	Merseyside
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	Newcastle	Tyne & Wear
United States	Research Site	Atlanta	Georgia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chesterfield	Missouri
United States	Research Site	Cleveland	Ohio
United States	Research Site	Falls Church	Virginia
United States	Reserach Site	Houston	Texas
United States	Research Site	Iowa City	Iowa
United States	Research Site	Kansas City	Missouri
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Los Angeles	California
United States	Research Site	Madison	Wisconsin
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Providence	Rhode Island
United States	Research Site	Rochester	Minnesota
United States	Research Site	Seattle	Washington
United States	Research Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Chile,  Czechia,  Denmark,  France,  Greece,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	Number of Participants With Anti-BG00011 Antibodies in the Serum		Up to Week 60 (End of Study)
Secondary	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)