Last reviewed · How we verify

NCT01766817

Safety and Efficacy of a Lysophosphatidic Acid Receptor Antagonist in Idiopathic Pulmonary Fibrosis

Completed Phase 2 Results posted Last updated 11 August 2020
What this trial tests

Phase 2 trial testing BMS-986020 in Idiopathic Pulmonary Fibrosis in 325 participants. Completed in 29 February 2016.

Timeline
31 January 2013
Primary endpoint
29 February 2016
29 February 2016

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment325
Start date31 January 2013
Primary completion29 February 2016
Estimated completion29 February 2016
Sites72 locations across Colombia, Peru, Chile, Mexico, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

Adults 40 to 90, any sex, with Idiopathic Pulmonary Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Forced Vital Capacity (FVC) Rate to Week 26 Primary · Baseline, Week 26

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.

GroupValue95% CI
BMS-986020 600 mg Once Daily-0.076± 0.2238
BMS-986020 600 mg Twice Daily-0.050± 0.2440
Placebo-0.136± 0.1804
Geometric Mean Ratio (GMR) of Quantitative Lung Fibrosis (QLF) Score at Week 26 to Baseline Secondary · Baseline, Week 26

The QLF score itself ranges from 0 to 100%, where greater values represent a greater amount of lung fibrosis and are considered a worse health status. Hence smaller geometric mean ratios to baseline were considered favorable. Baseline included all testing done on Day -1 as well as predose on Day 1.

GroupValue95% CI
BMS-986020 600 mg Once Daily1.14
BMS-986020 600 mg Twice Daily1.09
Placebo1.11
Mean Change From Baseline in Six-minute Walk Test (6MWT) Distance to Week 26 Secondary · Baseline, Week 26

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 included all testing done on Day -1 as well as predose on Day 1

GroupValue95% CI
BMS-986020 600 mg Once Daily-14.2± 47.85
BMS-986020 600 mg Twice Daily6.1± 53.87
Placebo10.3± 54.73
Mean Change From Baseline in the University of California at San Diego Shortness of Breath Questionnaire (UCSD SOBQ) Total Score as a Measure of Dyspnea to Week 26 Secondary · Baseline, Week 26

The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. Baseline included all testing done on Day -1 as well as predose on Day 1. The total score ranges from 0 to 120, with higher scores indicating worse dyspnea.

GroupValue95% CI
BMS-986020 600 mg Once Daily3.8± 17.84
BMS-986020 600 mg Twice Daily-1.7± 21.29
Placebo3.9± 18.24
Mean Change From Baseline in Forced Vital Capacity (FVC) to Week 26 Secondary · Baseline, Week 26

FVC is 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 lungs after taking an inhaled bronchodilator medicine which is used to dilate bronchial (breathing) tubes. Baseline included all testing done on Day -1 as well as predose on Day 1

GroupValue95% CI
BMS-986020 600 mg Once Daily-0.076± 0.2238
BMS-986020 600 mg Twice Daily-0.050± 0.2440
Placebo-0.136± 0.1804
Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36) to Week 26 Secondary · Baseline, Week 26

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the Aggregate Physical score of the SF-36. Items 5-8 primarily contribute to the Aggregate mental score of the SF-36. Scores on each item a

Aggregate Physical Score
GroupValue95% CI
BMS-986020 600 mg Once Daily-3.4± 1.0
BMS-986020 600 mg Twice Daily-1.0± 1.0
Placebo-2.1± 1.1
Aggregate Mental Score
GroupValue95% CI
BMS-986020 600 mg Once Daily0.1± 1.3
BMS-986020 600 mg Twice Daily1.7± 1.3
Placebo-1.1± 1.3
Number of Participants With Death or Non-Elective Hospitalization Secondary · Upto Day 210

Time to death or non-elective hospitalization was defined as the elapsed time (days) from randomization to the date of death or the first non-elective hospitalization.

GroupValue95% CI
BMS-986020 600 mg Once Daily5
BMS-986020 600 mg Twice Daily4
Placebo2
Number of Participants With Death or Respiratory Hospitalization or 10 Percent (%) Decline in Absolute Volume of FVC or 25-Meter Loss in 6-Minute Walk Distance (6MWD) Secondary · Upto Day 210

Number of participants with death or respiratory hospitalization or 10% decline in absolute volume of FVC or 25 meter loss in 6MWD over time were reported.

GroupValue95% CI
BMS-986020 600 mg Once Daily24
BMS-986020 600 mg Twice Daily28
Placebo26
Mean Change From Baseline in Carbon Monoxide Diffusing Capacity (DLCO) to Week 26 Secondary · Baseline, Week 26

DLCO is a measurement of the ability of the lungs to transfer gases from the air to the blood. Participant breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participant hold the breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine how much of the tracer gas was absorbed during the breath. DLCO, both uncorrected and corrected for hemoglobin in milliliter per minute per millimeter of mercury (mL/min/mmHg) was assessed.

Uncorrected for hemoglobin
GroupValue95% CI
BMS-986020 600 mg Once Daily-1.1± 0.7
BMS-986020 600 mg Twice Daily-0.2± 0.7
Placebo-1.1± 0.7
Corrected for hemoglobin
GroupValue95% CI
BMS-986020 600 mg Once Daily-1.2± 0.7
BMS-986020 600 mg Twice Daily-0.2± 0.7
Placebo-1.1± 0.7
Number of Participants With Definite or Probable Acute Exacerbation (AEx) of Idiopathic Pulmonary Fibrosis (IPF) Secondary · Upto Day 210

Acute IPF exacerbations is defined as a clinically significant deterioration of unidentifiable cause in a participant with underlying IPF. Exacerbations of IPF were adjudicated as definite (\>=1 AEx) and Probable. Investigators were asked to make the diagnosis of acute exacerbation of IPF on the basis of subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The final diagnosis, however, was confirmed by the study medical monitor.

Definite
GroupValue95% CI
BMS-986020 600 mg Once Daily0
BMS-986020 600 mg Twice Daily2
Placebo0
Probable
GroupValue95% CI
BMS-986020 600 mg Once Daily1
BMS-986020 600 mg Twice Daily1
Placebo0
Maximum Observed Plasma Concentration (Cmax) BMS-986020 Secondary · Day 1 and Day 7

Cmax is defined as the maximum observed plasma concentration.

Day 1
GroupValue95% CI
BMS-986020 600 mg Once Daily5963.7± 65
BMS-986020 600 mg Twice Daily3005.8± 104
Day 7
GroupValue95% CI
BMS-986020 600 mg Once Daily6535.4± 68
BMS-986020 600 mg Twice Daily7266.2± 51
Time of Maximum Observed Plasma Concentration (Tmax) of BMS-986020 Secondary · Day 1 and Day 7

Tmax is defined as the maximum observed plasma concentration.

Day 1
GroupValue95% CI
BMS-986020 600 mg Once Daily3.1101.07 – 6.00
BMS-986020 600 mg Twice Daily2.0301.00 – 4.00
Day 7
GroupValue95% CI
BMS-986020 600 mg Once Daily3.0001.02 – 4.00
BMS-986020 600 mg Twice Daily2.0000.50 – 3.00

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events were collected from signature of the informed consent until 4 weeks after last treatment administration. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BMS-986020 600 mg Once Daily
Serious: 9/48 (19%)
Deaths: 2/48
BMS-986020 600 mg Twice Daily
Serious: 16/48 (33%)
Deaths: 2/48
Placebo
Serious: 12/47 (26%)
Deaths: 1/47

Serious adverse events (25 terms)

ReactionSystemBMS-986020 600 mg Once DailyBMS-986020 600 mg Twice Da…Placebo
OverdoseInjury, poisoning and procedural complications
Idiopathic pulmonary fibrosisRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
Acute myocardial infarctionCardiac disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
Pulmonary hypertensionRespiratory, thoracic and mediastinal disorders
BronchitisInfections and infestations
SinusitisInfections and infestations
Cardiogenic shockCardiac disorders
Coronary artery diseaseCardiac disorders
Diverticular perforationGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
Intestinal ischaemiaGastrointestinal disorders
PancreatitisGastrointestinal disorders
Gallbladder necrosisHepatobiliary disorders
Gallbladder perforationHepatobiliary disorders
HydrocholecystisHepatobiliary disorders
Peripheral vascular disorderVascular disorders
Temporal arteritisVascular disorders
AnaemiaBlood and lymphatic system disorders
Cerebrovascular accidentNervous system disorders
Diabetic footSkin and subcutaneous tissue disorders
Other adverse events (21 terms — click to expand)

ReactionSystemBMS-986020 600 mg Once DailyBMS-986020 600 mg Twice Da…Placebo
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
HeadacheNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
BronchitisInfections and infestations
Blood alkaline phosphatase increasedInvestigations
Idiopathic pulmonary fibrosisRespiratory, thoracic and mediastinal disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
DizzinessNervous system disorders
Hepatic enzyme increasedInvestigations
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
GastritisGastrointestinal disorders
NauseaGastrointestinal disorders
PharyngitisInfections and infestations
RashSkin and subcutaneous tissue disorders
SinusitisInfections and infestations
Transaminases increasedInvestigations

Most-reported serious reactions: Overdose, Idiopathic pulmonary fibrosis, Pneumonia, Acute myocardial infarction, Acute respiratory failure, Dyspnoea, Hypoxia, Interstitial lung disease.

Data from ClinicalTrials.gov NCT01766817 adverse events section.

Sponsor's own description

The purpose of this study is to determine if study drug (BMS-986020) dose of 600 mg once daily or 600 mg twice daily for 26 weeks compared with placebo will reduce the decline in forced vital capacity (FVC) and will be well tolerated in subjects with idiopathic pulmonary fibrosis (IPF).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets.
    Ballester B, Milara J, Cortijo J. · · 2019 · cited 243× · PMID 30704051 · DOI 10.3390/ijms20030593
  2. Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.
    Geraldo LHM, Spohr TCLS, Amaral RFD, Fonseca ACCD, et al · · 2021 · cited 221× · PMID 33526777 · DOI 10.1038/s41392-020-00367-5
  3. New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses.
    Ahluwalia N, Shea BS, Tager AM. · · 2014 · cited 186× · PMID 25090037 · DOI 10.1164/rccm.201403-0509pp
  4. The Rho kinases: critical mediators of multiple profibrotic processes and rational targets for new therapies for pulmonary fibrosis.
    Knipe RS, Tager AM, Liao JK. · · 2015 · cited 171× · PMID 25395505 · DOI 10.1124/pr.114.009381
  5. Lysophospholipid receptors in drug discovery.
    Kihara Y, Mizuno H, Chun J. · · 2015 · cited 159× · PMID 25499971 · DOI 10.1016/j.yexcr.2014.11.020
  6. Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis.
    Palmer SM, Snyder L, Todd JL, Soule B, et al · · 2018 · cited 137× · PMID 30201408 · DOI 10.1016/j.chest.2018.08.1058
  7. Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways.
    Suryadevara V, Ramchandran R, Kamp DW, Natarajan V. · · 2020 · cited 111× · PMID 32549377 · DOI 10.3390/ijms21124257
  8. MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia.
    Plastira I, Bernhart E, Joshi L, Koyani CN, et al · · 2020 · cited 110× · PMID 32326963 · DOI 10.1186/s12974-020-01809-1

Verify or expand the search:

Other recruiting trials for Idiopathic Pulmonary Fibrosis

Currently open trials in the same condition.

Other Bristol-Myers Squibb trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01766817.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing