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

NCT ID: NCT01766817

Last Updated: 2020-08-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

325 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2016-02-29

Brief Summary

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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).

Detailed Description

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Conditions

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Idiopathic Pulmonary Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Arm 1: BMS 986020, 600 mg. once daily

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

Group Type EXPERIMENTAL

BMS-986020

Intervention Type DRUG

Arm 2: BMS-986020, 600 mg twice daily

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

Group Type EXPERIMENTAL

BMS-986020

Intervention Type DRUG

Arm 3: Placebo matching with BMS-986020

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

Group Type PLACEBO_COMPARATOR

Placebo matching with BMS-986020

Intervention Type DRUG

Interventions

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BMS-986020

Intervention Type DRUG

Placebo matching with BMS-986020

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

1. Women must have a negative urine pregnancy test within 24 hours prior to the start of investigational product.
2. Women must not be breastfeeding.
3. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men that are sexually active with 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 90 days after the last dose of investigational product.
4. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception.

Exclusion Criteria

Target Disease Exclusions

1. Has significant clinical worsening of IPF between screening and day 1 (during the screening process), in the opinion of the investigator.
2. Has forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.8 after administration of bronchodilator at screening.
3. 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

1. 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.
2. 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.
3. 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.
4. Currently has clinically significant asthma or chronic obstructive pulmonary disease.
5. Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, and cellulitis.
6. 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).
7. 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.
8. Has a history of end-stage liver disease.
9. Has a history of end-stage renal disease requiring dialysis.
10. 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
11. 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.
12. Has a history of alcohol or substance abuse in the past 2 years.
13. Has a family or personal history of long QT syndrome and/or Torsades de Pointes (polymorphic ventricular tachycardia).
14. Has used any of the excluded medications per Appendix 1 of the Protocol, which includes, but is not limited to:

* current treatment with pirfenidone or nintedanib
* use of over-the-counter medications and herbal preparations, within 4 weeks before study drug administration except those medications cleared by the BMS medical monitor
* For subjects taking statins, there are restrictions on the maximum allowable doses for statins listed below. If subjects are currently taking statins and their doses are higher than those mentioned below, please reduce the dose to the maximum allowable dose.

Additionally, if subjects are on statins and ready to start dosing, these subjects should limit statin doses by maximal allowable dose or lower for at least 5 days prior to the first BMS-986020 dosing. Shorter durations may be considered in select cases after discussion with the medical monitor.

Maximum allowable dose for statins:

* Simvastatin 20 mg QD
* Pitavastatin 2 mg QD
* Atorvastatin 40 mg QD
* Pravastatin 40 mg QD
* Rosuvastatin 20 mg QD
* Lovastatin 40 mg QD
* Fluvastatin 40 mg QD
* Prednisone is allowed up to a maximum of 15 mg po daily
* Pirfenidone or nintedanib dosing for a maximum of 3 months in the prior 12 months is permitted with a 4 week washout period prior to dosing with BMS-986020.

Physical and Laboratory Test Findings

1. Has any of the following liver-function test criteria above the specified limits: total bilirubin \>1.5 x ULN, excluding subjects with Gilbert's syndrome; aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) greater than 3 x ULN; alkaline phosphatase greater than 2.5 x ULN.
2. Has creatinine clearance less than 30 mL/minute, calculated using the Cockcroft-Gault formula.
3. Has ECG result with a QT interval by Fridericia's correction (QTcF) of 500 msec or greater or an uncorrected QT of 500 msec or greater at screening. Note: For subjects with a machine read QT interval of \>500 msec, if their heart rate is \> 100 bpm, the machine read QT interval (either corrected or not) may not be accurate. If the investigator is uncertain about the QT abnormality, it is recommended that ECGs be over-read by a cardiologist. The manually read QT interval by a cardiologist should be used for assessment of eligibility whenever possible.

Allergies and Adverse Drug Reaction Has had prior use of BMS-986020 or has known hypersensitivity to any of the components of study treatment.


1. Is not a suitable candidate for enrollment or is unlikely to comply with the requirements of this study, in the opinion of the investigator.
2. Has smoked cigarettes within 4 weeks or screening or is unwilling to avoid tobacco products throughout the study.
3. Is expected to receive a lung transplant within 1 year from randomization or, for subjects at sites in the United States, is on a lung-transplant waiting list at screening.
4. Prisoners or subjects who are involuntarily incarcerated.
5. Subjects who are compulsorily detained for treatment either of a psychiatric or physical (e.g., infectious disease) illness.
6. Inability to comply with restrictions and prohibited activities/treatments as listed in Section 3.3 of the Protocol.
Minimum Eligible Age

40 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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

Birmingham, Alabama, United States

Site Status

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

Phoenix, Arizona, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status

University of California at San Francisco

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

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

New Haven, Connecticut, United States

Site Status

Advanced Pulmonary & Sleep Research Institute of Florida

Daytona Beach, Florida, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

ILD Research Center

Miami, Florida, United States

Site Status

Cleveland Clinic Florida- Weston Hospital

Weston, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Via Christi Clinic

Wichita, Kansas, United States

Site Status

University of Kentucky- Center for Clinical and Translational Science

Lexington, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Tulane University

New Orleans, Louisiana, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic, Pulmonary Clinical Research Unit

Rochester, Minnesota, United States

Site Status

CardioPulmonary Research Center

Chesterfield, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Pulmonary & Allergy Associates, PA

Summit, New Jersey, United States

Site Status

ISA Clinical Research

Forest Hills, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Highland Hospital

Rochester, New York, United States

Site Status

Asheville Pulmonary and Critical Care Associates, P.A.

Asheville, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University of Cincinnati Pulmonary, Critical Care & Sleep Medicine

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

The Oregon Clinic

Portland, Oregon, United States

Site Status

Oregon Health Science University

Portland, Oregon, United States

Site Status

Temple Lung Center

Philadelphia, Pennsylvania, United States

Site Status

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

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Metroplex Pulmonary and Sleep Center

McKinney, Texas, United States

Site Status

Alamo Clinical Research

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at Tyler

Tyler, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Vermont Lung Center

Colchester, Vermont, United States

Site Status

Inova Fairfax Medical Campus

Falls Church, Virginia, United States

Site Status

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, United States

Site Status

Local institution

Westmead, New South Wales, Australia

Site Status

Local institution

Greenslopes, Queensland, Australia

Site Status

Local Institution

Adelaide, South Australia, Australia

Site Status

Local institution

Frankston, Victoria, Australia

Site Status

Local institution

Nedlands, Western Australia, Australia

Site Status

Local institution

Viña del Mar, Región de Valparaíso, Chile

Site Status

Local institution

Quillota, , Chile

Site Status

Local institution

Santiago, , Chile

Site Status

Local Institution

Talca, , Chile

Site Status

Hospital Pablo Tobon Uribe

Medellín, Antioquia, Colombia

Site Status

Fundacion Neumologica Colombiana

Bogota, Cundinamarca, Colombia

Site Status

Hospital Universitario San Ignacio

Bogota, Cundinamarca, Colombia

Site Status

Local Institution

Bogota, Cundinamarca, Colombia

Site Status

Local Institution

Guadalajara, Jalisco, Mexico

Site Status

Local Institution

Mexico City, Mexico City, Mexico

Site Status

Local Institution

Mexico City, Mexico City, Mexico

Site Status

Local Institution

Monterrey, Nuevo León, Mexico

Site Status

Local Institution

Monterrey, Nuevo León, Mexico

Site Status

Local Institution

Monterrey, Nuevo León, Mexico

Site Status

Local institution

Lima, , Peru

Site Status

Local Institution

Lima, , Peru

Site Status

Local institution

Lima, , Peru

Site Status

Local institution

Lima, , Peru

Site Status

Local institution

Lima, , Peru

Site Status

Countries

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United States Australia Chile Colombia Mexico Peru

References

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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.

Reference Type DERIVED
PMID: 35303880 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30201408 (View on PubMed)

Other Identifiers

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IM136-003

Identifier Type: -

Identifier Source: org_study_id

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