Phase ll Study of Pirfenidone in Patients With RAILD (TRAIL1)

NCT02808871 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2017p000062
• Study Type: interventional
• Target: 123
• Locations: 4 countries
• Sites: 33

Brief Summary

The purpose of this study is to to assess the safety and tolerability of pirfenidone 2403 mg/day for the treatment of RA-associated interstitial lung disease.

Conditions

Rheumatoid Arthritis Interstitial Lung Disease

Keywords

TRAIL1; TRAIL; Pirfenidone

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Developed Any Element of the Composite Endpoint

  Number of participants who developed any element of the composite endpoint of decline in percent predicted FVC of 10% or greater or death.

  52 weeks

Secondary Outcomes (17)

• Number of Participants With FVC Decline From Baseline of 10% or Greater

  52 weeks

• Number of Participants With Progressive Disease

  52 weeks

• Change in Absolute Value FVC Over the 52 Week Study Period

  52 weeks

• Change in % Predicted FVC From Baseline to End of Study Over the 52 Week Study Period

  52 weeks

• Time to Composite of Decline in FVC or Death

  52 weeks

Other Outcomes (11)

• Disease Activity Score (DAS)

  52 weeks

• RAPID3 Score

  52 weeks

• Erythrocyte Sedimentation Rate (ESR)

  52 weeks

Study Arms (2)

Pirfenidone

EXPERIMENTAL

Pirfenidone 2403 mg/d for 52 weeks

Drug: Pirfenidone

Placebo

PLACEBO COMPARATOR

Placebo for 52 weeks

Drug: Placebo

Interventions

Pirfenidone DRUG

Pirfenidone three times daily (2403 mg) for 52 weeks

Also known as: Esbriet

Pirfenidone

Placebo DRUG

Placebo three times daily for 52 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator
• Cigarette smoking or vaping within 3 months of Screening or unwilling to avoid tobacco products throughout the study
• History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds
• Concurrent presence of the following conditions:
• Other interstitial lung disease, related to but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, or bronchiolitis obliterans organizing pneumonia
• Medical history including Human Immunodeficiency Virus (HIV)
• Concurrent presence of other pleuropulmonary manifestations of RA, including but not limited to rheumatoid nodular disease of the lung, pleuritis/pleural thickening, and obliterative bronchiolitis
• Post-bronchodilator FEV1/FVC \<0.65 at Screening
• Presence of pleural effusion occupying more than 20% of the hemithorax on Screening HRCT
• Clinical diagnosis of a second connective tissue disease or overlap syndrome (including but not limited to scleroderma, sjogren's, polymyositis/dermatomyositis, systemic lupus erythematosus but excluding Raynaud's phenomena)
• Coexistent clinically significant COPD/emphysema or asthma in the opinion of the site principal investigator
• Any history of malignancy diagnosed within 5 years of screening, other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or low grade cervical carcinoma, and/or low grade prostate cancer.
• Criteria for low grade prostate cancer:
• Patients with suspicion for prostate cancer based on PSA and/or DRE should have been evaluated by urology
• Patients with NCCN very low risk prostate cancer (∙ T1c and Grade Group 1 (Gleason 6) and PSA \<10 ng/mL and Fewer than 3 prostate biopsy fragments/cores positive, ≤50% cancer in each fragment/coreg and ∙ PSA density \<0.15 ng/mL/g) can be monitored without intervention and enrolled in study.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (33)

University of Alabama Site at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

John Hopkins Medicine

Baltimore, Maryland, 21224, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Utah Health Care

Salt Lake City, Utah, 84132, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Royal Brompton

Brisbane, Queensland, 4032, Australia

Location

Royal Prince Alfred Hospital

Camperdown, Sydney, NSW 2050, Australia

Location

Melbourne Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

The Prince Charles Hospital

Camperdown, 2050, Australia

Location

University of Calgary Cummings School of Medicine

Calgary, Alberta, T3M 1M4, Canada

Location

St. Paul's Hospital - Providence Health Care

Vancouver, British Columbia, V6Z1Y6, Canada

Location

St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

North Bristol NHS Trust Headquarters, Southmead Hospital

Bristol, BS10 5NB, United Kingdom

Location

Papworth Hospital NHS Foundation Trust

Cambridge, CB23 3RE, United Kingdom

Location

Royal Devon and Exeter NHS Foundation

Exeter, EX2 5DW, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

University Hospitals of Leicester NHS Foundation Trust

Leicester, LE3 9QP, United Kingdom

Location

Aintree University Hospitals NHS Foundation Trust

Liverpool, L9 7AL, United Kingdom

Location

Royal Brompton and Harefield NHS Foundation Trust

London, SW3 6NP, United Kingdom

Location

Manchester University NHS Foundation Trust (South) Wythenshawe Hospita

Manchester, M23 9LT, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, NR4 7UY, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southhampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• Solomon JJ, Danoff SK, Woodhead FA, Hurwitz S, Maurer R, Glaspole I, Dellaripa PF, Gooptu B, Vassallo R, Cox PG, Flaherty KR, Adamali HI, Gibbons MA, Troy L, Forrest IA, Lasky JA, Spencer LG, Golden J, Scholand MB, Chaudhuri N, Perrella MA, Lynch DA, Chambers DC, Kolb M, Spino C, Raghu G, Goldberg HJ, Rosas IO; TRAIL1 Network Investigators. Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Respir Med. 2023 Jan;11(1):87-96. doi: 10.1016/S2213-2600(22)00260-0. Epub 2022 Sep 5.

  PMID: 36075242 DERIVED

• Solomon JJ, Danoff SK, Goldberg HJ, Woodhead F, Kolb M, Chambers DC, DiFranco D, Spino C, Haynes-Harp S, Hurwitz S, Peters EB, Dellaripa PF, Rosas IO; Trail Network. The Design and Rationale of the Trail1 Trial: A Randomized Double-Blind Phase 2 Clinical Trial of Pirfenidone in Rheumatoid Arthritis-Associated Interstitial Lung Disease. Adv Ther. 2019 Nov;36(11):3279-3287. doi: 10.1007/s12325-019-01086-2. Epub 2019 Sep 12.

  PMID: 31515704 DERIVED

MeSH Terms

Interventions

pirfenidone

Results Point of Contact

• Title: Ivan O. Rosas, MD
• Organization: Baylor College of Medicine

Ivan.Rosas@bcm.edu

617-510-9910

Study Officials

• Ivan O. Rosas, M.D.

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: March 20, 2016
• First Posted: June 22, 2016
• Study Start: April 7, 2017
• Primary Completion: April 7, 2021
• Study Completion: April 7, 2021
• Last Updated: August 16, 2022
• Results First Posted: August 16, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); CA (4); GB (12); AU (4)