Clinical trial NCT04308681: A Study Measuring the Effectiveness, Safety, and Tolerability of BMS-986278 in Participants With Lung Fibrosis
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study of the Efficacy and the Safety and Tolerability of BMS-986278 in Participants With Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Fibrosis
Keywords: Idiopathic pulmonary fibrosis
Progressive Fibrotic Interstitial Lung Disease
Idiopathic interstitial pneumonia
Fibrotic interstitial pneumonia
Fibrotic interstitial lung disease
Fibrosing interstitial lung disease
Interstitial lung disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2020-03-16
Enrollment: 403
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to provide an initial evaluation of the effectiveness of BMS-986278 in participants with lung fibrosis, to demonstrate the safety of BMS-986278, and provide information on the drug levels of BMS-986278 in these participants.


Eligibility criteria: Inclusion Criteria:

For the idiopathic pulmonary fibrosis (IPF) Cohort

* Diagnosis of IPF within 7 years of screening
* Female and males ≥ 40 years of age

For the progressive fibrotic interstitial lung disease (PF-ILD) Cohort

* Evidence of progressive ILD within the 24 months before screening
* Female and male ≥ 21 years of age.

Exclusion Criteria:

* Women of childbearing potential (WOCBP)
* Active Smokers
* Current malignancy or previous malignancy up to 5 years prior to screening
* History of allergy to BMS-986278 or related compounds

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) in IPF Participants
timeFrame: From baseline (first dose) up to week 26
Secondary outcomes:
measure: The Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From first dose up to 30 days after last dose during the main study treatment phase
measure: The Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: From first dose up to 30 days after last dose during the main study treatment phase
measure: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
timeFrame: From first dose up to 30 days after last dose during the main study treatment phase
measure: The Number of Participants Who Died Due to Adverse Events (AEs)
timeFrame: From first dose up to 30 days after last dose during the main study treatment phase
measure: Maximum Concentration (Cmax)
timeFrame: On Day 1 and Week 4 (Day 29)
measure: Time to Maximum Concentration (Tmax)
timeFrame: On Day 1 and Week 4 (Day 29)
measure: Area Under Curve (AUC0-8)
timeFrame: On Day 1 and Week 4 (Day 29)
measure: Concentration Trough (Ctrough)
timeFrame: On Week 4 (Day 29) and Week 12 (Day 85)
measure: The Number of Participants Experiencing Electrocardiogram (ECG) Abnormalities
timeFrame: At Week 26
measure: Change From Baseline in Vital Sign Measurements
timeFrame: At baseline and Week 26
measure: Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) in PF-ILD Participants
timeFrame: At baseline and Week 26
measure: The Number of Participants With ≥ 10% Absolute Decline in ppFVC (%)
timeFrame: At Weeks 4, 8, 12, 16, 20, and 26
measure: The Number of Participants With 0% Change in ppFVC (%)
timeFrame: Weeks 4, 8, 12, 16, 20, and 26
measure: Time to First Occurrence ≥ 10% Absolute Decline in ppFVC (%)
timeFrame: From first dose up to the first occurrence of ≥ 10% absolute decline in ppFVC
measure: Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC)
timeFrame: From baseline up to Weeks 4, 8, 12, 16, 20, and 26
measure: Absolute Change From Baseline in Forced Vital Capacity (FVC)
timeFrame: From baseline up to Weeks 4, 8, 12, 16, 20, and 26
measure: Absolute Change From Baseline in Single Breath Diffusing Capacity of Carbon Monoxide (DLCO SB)
timeFrame: From baseline up to Week 26
measure: Absolute Change From Baseline in Percent Predicted Single Breath Diffusing Capacity of Carbon Monoxide (ppDLCO SB)
timeFrame: From baseline up to Week 26
measure: Absolute Change From Baseline in Walking Endurance/Distance
timeFrame: From baseline up to Week 26
measure: Time to First Acute Exacerbation
timeFrame: From the first dose up to the day of the first acute exacerbation or Week 26, whichever comes first
measure: The Number of Participants Experiencing Acute Exacerbation
timeFrame: From the first dose up to the day of the first acute exacerbation or Week 26, whichever comes first
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0032
state: Alabama
city: Phoenix
country: United States
facility: Local Institution
state: Arizona
city: Los Angeles
country: United States
facility: Local Institution - 0028
state: California
city: Stanford
country: United States
facility: Local Institution - 0043
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus-Department of Medicine
state: Colorado
city: Denver
country: United States
facility: Local Institution - 0006
state: Colorado
city: New Haven
country: United States
facility: Local Institution - 0171
state: Connecticut
city: Gainesville
country: United States
facility: Local Institution - 0035
state: Florida
city: Orlando
country: United States
facility: Local Institution - 0166
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0078
state: Georgia
city: Kansas City
country: United States
facility: Local Institution - 0031
state: Kansas
city: Baltimore
country: United States
facility: Local Institution - 0154
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0003
state: Massachusetts
city: Chesterfield
country: United States
facility: Local Institution - 0030
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 0036
state: Missouri
city: Cincinnati
country: United States
facility: Local Institution - 0029
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0164
state: Ohio
city: Hershey
country: United States
facility: Local Institution
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution
state: Tennessee
city: Charlottesville
country: United States
facility: Local Institution - 0096
state: Virginia
city: Falls Church
country: United States
facility: Local Institution
state: Virginia
city: Buenos Aires
country: Argentina
facility: Local Institution - 0049
state: Distrito Federal
city: Rosario
country: Argentina
facility: Local Institution - 0103
state: Santa FE
city: San Miguel de Tucuman
country: Argentina
facility: Local Institution - 0097
state: Tucuman
city: Buenos AIres
country: Argentina
facility: Local Institution - 0115
city: Buenos Aires
country: Argentina
facility: Local Institution - 0048
city: Mendoza
country: Argentina
facility: Local Institution - 0122
city: Camperdown
country: Australia
facility: Local Institution - 0045
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 0025
state: New South Wales
city: Brisbane
country: Australia
facility: Local Institution - 0026
state: Queensland
city: Greenslopes
country: Australia
facility: Local Institution - 0046
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution - 0022
state: South Australia
city: Heidelberg
country: Australia
facility: Local Institution - 0023
state: Victoria
city: Murdoch
country: Australia
facility: Local Institution - 0021
state: Western Australia
city: Nedlands
country: Australia
facility: Local Institution - 0044
state: Western Australia
city: Brussels
country: Belgium
facility: Local Institution - 0074
city: Leuven
country: Belgium
facility: Local Institution - 0065
city: Liège
country: Belgium
facility: Local Institution - 0051
city: Porto Alegre
country: Brazil
facility: Local Institution
state: RIO Grande DO SUL
city: São Paulo
country: Brazil
facility: Local Institution
state: SAO Paulo
city: São Paulo
country: Brazil
facility: Local Institution
state: SAO Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution - 0076
city: Vancouver
country: Canada
facility: Local Institution - 0141
state: British Columbia
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution - 0134
state: Ontario
city: Montréal
country: Canada
facility: Local Institution - 0094
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution - 0144
state: Quebec
city: Quebec
country: Canada
facility: Local Institution - 0127
city: Curicó
country: Chile
facility: Local Institution - 0108
state: Maule
city: Talca
country: Chile
facility: Local Institution - 0054
state: Maule
city: Quillota
country: Chile
facility: Local Institution - 0038
state: Valparaiso
city: Beijing
country: China
facility: Local Institution - 0187
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0183
state: Beijing
city: Wuhan
country: China
facility: Local Institution - 0188
state: Hubei
city: Shanghai
country: China
facility: Local Institution - 0189
state: Shanghai
city: Bobigny
country: France
facility: Local Institution - 0120
city: Bron
country: France
facility: Local Institution - 0066
city: Dijon
country: France
facility: Local Institution - 0136
city: Marseille
country: France
facility: Local Institution - 0162
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Local Institution - 0143
city: Rennes
country: France
facility: Local Institution - 0067
city: Toulouse
country: France
facility: Local Institution - 0132
city: Hannover
country: Germany
facility: Local Institution - 0111
state: Niedersachsen
city: Essen
country: Germany
facility: Local Institution - 0107
city: Freiburg
country: Germany
facility: Local Institution
city: Grosshansdorf
country: Germany
facility: Local Institution - 0093
city: Heidelberg
country: Germany
facility: Local Institution - 0110
city: Munich
country: Germany
facility: Local Institution - 0121
city: Stuttgart
country: Germany
facility: Local Institution - 0119
city: Tel Aviv
country: Israel
facility: Local Institution - 0145
state: Tel-Aviv
city: Haifa
country: Israel
facility: Local Institution - 0113
city: Jerusalem
country: Israel
facility: Local Institution - 0149
city: Petah Tikva
country: Israel
facility: Local Institution - 0114
city: Ramat Gan
country: Israel
facility: Local Institution - 0148
city: Catania
country: Italy
facility: Local Institution - 0073
city: Modena
country: Italy
facility: Local Institution - 0077
city: Monza
country: Italy
facility: Local Institution - 0089
city: Roma
country: Italy
facility: Local Institution - 0072
city: Seto
country: Japan
facility: Local Institution - 0155
state: Aichi
city: Koriyama
country: Japan
facility: Local Institution - 0106
state: Fukushima
city: Sapporo
country: Japan
facility: Local Institution - 0180
state: Hokkaido
city: Kobe
country: Japan
facility: Local Institution - 0095
state: Hyogo
city: Kobe
country: Japan
facility: Local Institution - 0169
state: Hyogo
city: Yokohama
country: Japan
facility: Local Institution - 0071
state: Kanagawa
city: Sakai
country: Japan
facility: Local Institution - 0112
state: Osaka
city: Izumo
country: Japan
facility: Local Institution - 0128
state: Shimane
city: Hamamatasu
country: Japan
facility: Local Institution - 0064
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0080
state: Tokyo
city: Minato-ku
country: Japan
facility: Local Institution - 0153
state: Tokyo
city: Shinjyuku-ku
country: Japan
facility: Local Institution - 0177
state: Tokyo
city: Kumamoto
country: Japan
facility: Local Institution - 0117
city: Nagasaki
country: Japan
facility: Local Institution - 0146
city: Saitama
country: Japan
facility: Local Institution - 0170
city: Tokyo
country: Japan
facility: Local Institution - 0173
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0087
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0086
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Monterrey, N.l.
country: Mexico
facility: Local Institution - 0109
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution - 0081
state: Nuevo LEON
city: San Nicolas de los Garza
country: Mexico
facility: Local Institution - 0083
state: Nuevo LEON
city: Oaxaca de Juarez
country: Mexico
facility: Local Institution - 0156
state: Oaxaca
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution - 0116
city: L'Hospitalet de Llobregat
country: Spain
facility: Local Institution - 0140
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution - 0137
city: Marbella Málaga
country: Spain
facility: Local Institution
city: Pozuelo de Alarcon
country: Spain
facility: Local Institution - 0039
city: Santander
country: Spain
facility: Local Institution - 0147
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0176
city: Taipei
country: Taiwan
facility: Local Institution - 0174
city: Taipei
country: Taiwan
facility: Local Institution - 0175
city: Cambridge
country: United Kingdom
facility: Local Institution - 0050
city: Edinburgh
country: United Kingdom
facility: Local Institution - 0163
city: London
country: United Kingdom
facility: Local Institution - 0041
city: London
country: United Kingdom
facility: Local Institution - 0092
city: London
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Corte TJ, Lancaster L, Swigris JJ, Maher TM, Goldin JG, Palmer SM, Suda T, Ogura T, Minnich A, Zhan X, Tirucherai GS, Elpers B, Xiao H, Watanabe H, Smith RA, Charles ED, Fischer A. Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD). BMJ Open Respir Res. 2021 Dec;8(1):e001026. doi: 10.1136/bmjresp-2021-001026.
citation: Cheng PTW, Kaltenbach RF 3rd, Zhang H, Shi J, Tao S, Li J, Kennedy LJ, Walker SJ, Shi Y, Wang Y, Dhanusu S, Reddigunta R, Kumaravel S, Jusuf S, Smith D, Krishnananthan S, Li J, Wang T, Heiry R, Sum CS, Kalinowski SS, Hung CP, Chu CH, Azzara AV, Ziegler M, Burns L, Zinker BA, Boehm S, Taylor J, Sapuppo J, Mosure K, Everlof G, Guarino V, Zhang L, Yang Y, Ruan Q, Xu C, Apedo A, Traeger SC, Cvijic ME, Lentz KA, Tirucherai G, Sivaraman L, Robl J, Ellsworth BA, Rosen G, Gordon DA, Soars MG, Gill M, Murphy BJ. Discovery of an Oxycyclohexyl Acid Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist BMS-986278 for the Treatment of Pulmonary Fibrotic Diseases. J Med Chem. 2021 Nov 11;64(21):15549-15581. doi: 10.1021/acs.jmedchem.1c01256. Epub 2021 Oct 28.