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

NCT01766817 | Completed Phase 2 Results DMC

• 1 other identifier: IM136-003
• Study Type: interventional
• Target: 325
• Locations: 6 countries
• Sites: 72

Brief Summary

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).

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

IPF

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Forced Vital Capacity (FVC) Rate to 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.

  Baseline, Week 26

Secondary Outcomes (16)

• Geometric Mean Ratio (GMR) of Quantitative Lung Fibrosis (QLF) Score at Week 26 to Baseline

  Baseline, Week 26

• Mean Change From Baseline in Six-minute Walk Test (6MWT) Distance to Week 26

  Baseline, Week 26

• 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

  Baseline, Week 26

• Mean Change From Baseline in Forced Vital Capacity (FVC) to Week 26

  Baseline, Week 26

• 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

  Baseline, Week 26

Study Arms (3)

Arm 1: BMS 986020, 600 mg. once daily

EXPERIMENTAL

BMS-986020, 600 mg tablets, by mouth, once daily, 26 weeks

Drug: BMS-986020

Arm 2: BMS-986020, 600 mg twice daily

EXPERIMENTAL

BMS-986020, 600 mg tablets, by mouth, twice daily, 26 weeks

Drug: BMS-986020

Arm 3: Placebo matching with BMS-986020

PLACEBO COMPARATOR

Placebo, 0 mg tablets, by mouth, twice daily, 26 weeks

Drug: Placebo matching with BMS-986020

Interventions

BMS-986020 DRUG

Arm 1: BMS 986020, 600 mg. once daily; Arm 2: BMS-986020, 600 mg twice daily

Placebo matching with BMS-986020 DRUG

Arm 3: Placebo matching with BMS-986020

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are between the ages of 40 and 90 years, inclusive, at randomization.
• Have clinical symptoms consistent with IPF.
• Have first received a diagnosis of IPF less than 6 years before randomization. The date of diagnosis is defined as the date of the first available imaging or surgical lung biopsy consistent with IPF/UIP.
• Have a diagnosis of usual interstitial pulmonary fibrosis (UIP) or IPF by HRCT or surgical lung biopsy (SLB).
• Extent of fibrotic changes (honeycombing, reticular changes) greater than the extent of emphysema on HRCT scan.
• Have no features supporting an alternative diagnosis on transbronchial biopsy, BAL, or SLB, if performed.
• Have percent predicted post-bronchodilator FVC between 45% and 90%, inclusive, at screening.
• Have a change in post-bronchodilator FVC (measured in liters) between screening and day 1 that is less than a 10% relative difference, calculated as: the absolute value of 100% \* (screening FVC (L) - day 1 FVC (L)) / screening FVC (L).
• Have carbon monoxide diffusing capacity (DLCO) between 30% and 80% (adjusted for hemoglobin and altitude), inclusive, at screening.
• Have no evidence of improvement in measures of IPF disease severity over the preceding year, in the investigator's opinion.
• Be able to walk 150 meters or more at screening.
• Demonstrate an exertional decrease in oxygen saturation of 2 percentage points or greater at screening (may be performed with supplemental oxygen titrating to keep oxygen saturation levels \>88%).
• Are able to understand and sign a written informed consent form.
• Are able to understand the importance of adherence to study treatment and the study protocol and are willing to comply with all study requirements, including the concomitant medication restrictions, throughout the study.
• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must use acceptable method(s) of contraception. The individual methods of contraception and duration should be determined in consultation with the investigator. WOCBP must follow instructions for birth control when the half-life of the investigational drug is less than 24 hours, contraception should be continued for a period of 30 days after the last dose of investigational product.

You may not qualify if:

• Has significant clinical worsening of IPF between screening and day 1 (during the screening process), in the opinion of the investigator.
• Has forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.8 after administration of bronchodilator at screening.
• Has bronchodilator response, defined by an absolute increase of 12% or greater and an increase of 200 mL in FEV1 or FVC or both after bronchodilator use compared with the values before bronchodilator use at screening.
• Medical History and Concurrent Diseases
• Has a history of clinically significant environmental exposure known to cause pulmonary fibrosis, including, but not limited to, drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds.
• Has a known explanation for interstitial lung disease, including, but not limited to, radiation, drug toxicity, sarcoidosis, hypersensitivity, pneumonitis, bronchiolitis, obliterans, organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer.
• Has a clinical diagnosis of any connective tissue disease, including, but not limited to, scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and undifferentiated connective tissue disease.
• Currently has clinically significant asthma or chronic obstructive pulmonary disease.
• Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, and cellulitis.
• Has any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 2 years. This does not include minor surgical procedures for localized cancer (e.g., basal cell carcinoma).
• Has any condition other than IPF that, in the opinion of the investigator, is likely to result in the death of the subject within the next 2 years.
• Has a history of end-stage liver disease.
• Has a history of end-stage renal disease requiring dialysis.
• Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months, including, but not limited to, the following: i. Unstable angina pectoris or myocardial infarction ii. Congestive heart failure requiring hospitalization iii. Uncontrolled clinically significant arrhythmias
• Has any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of BMS-986020.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (72)

University of Alabama at Birmingham - Division of Pulmonary, Allergy & Criticial Care

Birmingham, Alabama, 35294-0006, United States

Location

St. Joseph's Hospital and Medical Center - Heart Lung Institute/ Clinical Research

Phoenix, Arizona, 85013, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5236, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine, Section of Pulmonary & Critical Care

New Haven, Connecticut, 06511, United States

Location

Advanced Pulmonary & Sleep Research Institute of Florida

Daytona Beach, Florida, 32117, United States

Location

University of Florida

Gainesville, Florida, 32610-0225, United States

Location

ILD Research Center

Miami, Florida, 33136, United States

Location

Cleveland Clinic Florida- Weston Hospital

Weston, Florida, 33331, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Via Christi Clinic

Wichita, Kansas, 67028, United States

Location

University of Kentucky- Center for Clinical and Translational Science

Lexington, Kentucky, 40513, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109-5360, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic, Pulmonary Clinical Research Unit

Rochester, Minnesota, 55905, United States

Location

CardioPulmonary Research Center

Chesterfield, Missouri, 63017, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Pulmonary & Allergy Associates, PA

Summit, New Jersey, 07901, United States

Location

ISA Clinical Research

Forest Hills, New York, 11375, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Highland Hospital

Rochester, New York, 14620, United States

Location

Asheville Pulmonary and Critical Care Associates, P.A.

Asheville, North Carolina, 28801, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Pulmonary, Critical Care & Sleep Medicine

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

The Oregon Clinic

Portland, Oregon, 97220, United States

Location

Oregon Health Science University

Portland, Oregon, 97239, United States

Location

Temple Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center - Simmons Center for Interstitial Lung Disease

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 78212, United States

Location

Metroplex Pulmonary and Sleep Center

McKinney, Texas, 75069, United States

Location

Alamo Clinical Research

San Antonio, Texas, 78212, United States

Location

University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Vermont Lung Center

Colchester, Vermont, 05444, United States

Location

Inova Fairfax Medical Campus

Falls Church, Virginia, 22042, United States

Location

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, 53792, United States

Location

Local institution

Westmead, New South Wales, 2145, Australia

Location

Local institution

Greenslopes, Queensland, 4120, Australia

Location

Local Institution

Adelaide, South Australia, 5000, Australia

Location

Local institution

Frankston, Victoria, 3199, Australia

Location

Local institution

Nedlands, Western Australia, 6009, Australia

Location

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Viña del Mar, Región de Valparaíso, Chile

Location

Local institution

Quillota, Chile

Location

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Santiago, Chile

Location

Local Institution

Talca, 3465584, Chile

Location

Hospital Pablo Tobon Uribe

Medellín, Antioquia, Colombia

Location

Fundacion Neumologica Colombiana

Bogota, Cundinamarca, Colombia

Location

Hospital Universitario San Ignacio

Bogota, Cundinamarca, Colombia

Location

Local Institution

Bogota, Cundinamarca, Colombia

Location

Local Institution

Guadalajara, Jalisco, 44100, Mexico

Location

Local Institution

Mexico City, Mexico City, 14050, Mexico

Location

Local Institution

Mexico City, Mexico City, 14080, Mexico

Location

Local Institution

Monterrey, Nuevo León, 64460, Mexico

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Local Institution

Monterrey, Nuevo León, 64710, Mexico

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Local Institution

Monterrey, Nuevo León, 66465, Mexico

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Lima, 01, Peru

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Local Institution

Lima, 1, Peru

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Local institution

Lima, 27, Peru

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Local institution

Lima, 33, Peru

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Local institution

Lima, 41, Peru

Location

Related Publications (2)

• Decato BE, Leeming DJ, Sand JMB, Fischer A, Du S, Palmer SM, Karsdal M, Luo Y, Minnich A. LPA1 antagonist BMS-986020 changes collagen dynamics and exerts antifibrotic effects in vitro and in patients with idiopathic pulmonary fibrosis. Respir Res. 2022 Mar 18;23(1):61. doi: 10.1186/s12931-022-01980-4.

  PMID: 35303880 DERIVED

• Palmer SM, Snyder L, Todd JL, Soule B, Christian R, Anstrom K, Luo Y, Gagnon R, Rosen G. Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis. Chest. 2018 Nov;154(5):1061-1069. doi: 10.1016/j.chest.2018.08.1058. Epub 2018 Sep 7.

  PMID: 30201408 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Due to 3 SAE cases on active treatment, a decision was taken by the sponsor to immediately discontinue all study dosing and to implement additional post-treatment safety monitoring in the off-treatment follow-up period.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

clinical.trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2013
• First Posted: January 11, 2013
• Study Start: January 31, 2013
• Primary Completion: February 29, 2016
• Study Completion: February 29, 2016
• Last Updated: August 11, 2020
• Results First Posted: May 22, 2019

Record last verified: 2020-08

Locations

CL (4); CO (4); ME (6); PE (5); AU (5); US (48)