Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis

NCT02958917 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: HS-3034
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Patients are being offered participation in this pirfenidone trial because They have been diagnosed with fibrotic hypersensitivity pneumonitis (FHP), a type of interstitial lung disease (ILD). This is a disease where scarring of lung tissue occurs as the result of inhaling substances called antigens. These antigens can be substances such as molds, chemicals or dust. As a result of this scarring the lungs are is not able to move oxygen into the bloodstream to reach other organs. Currently over 1400 subjects have been treated with pirfenidone in 15 clinical trials. This drug has been approved by the Food and Drug Administration (FDA) for use in Idiopathic Pulmonary Fibrosis, a different type of ILD, but requires special permission for use in your condition. The use of pirfenidone has not been approved for the treatment of FHP. It is considered experimental treatment in this study.

Conditions

Interstitial Lung Disease

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline to Week 52 in Percent Predicted FVC.

  The primary efficacy analysis will estimate the mean rank change in percent predicted FVC from Baseline to Week 52. Data will be analyzed using a rank linear regression model with the rank change in percent predicted FVC from Baseline to Week 52 as the outcome variable and rank Baseline percent predicted FVC and HP therapy (placebo or pirfenidone) and concomitant immunosuppressive therapy as covariates. The treatment effect will be tested using the Wald test. The primary efficacy analysis will be tested at an alpha level of 0.05. Missing data due to reasons other than death will be replaced with imputed values using the MICE method (multiple imputations via chained equation). Subjects with missing assessments due to death will be ranked worse than those who remain alive. Subjects who die will be ranked according to the time until death, with the shortest time until death as the worst rank.

  Up to 52 weeks.

Secondary Outcomes (6)

• Number of Participants With Progression-free Survival (PFS) Defined as the Time From Study Treatment Randomization to the First Occurrence of Any of the Following Events:

  Up to 52 weeks.

• Slope of FVC Over Treatment Period.

  Up to 52 weeks.

• Mean Change in Percent Predicted DLCO

  Up to 52 weeks.

• Number of Participants With All-cause Hospitalization

  Up to 52 weeks.

• Number of Participant With Hospitalization for a Respiratory Cause

  Up to 52 weeks.

Other Outcomes (4)

• St. George's Respiratory Questionnaire.

  Up to 52 weeks.

• Living With Pulmonary Fibrosis Health-Related Quality of Life

  Up to 52 weeks.

• University of California at San Diego Shortness-of-Breath Questionnaire Score.

  Up to 52 weeks.

Study Arms (2)

pirfenidone 2403 mg/d

PLACEBO COMPARATOR

Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent.

Drug: Pirfenidone; Other: Placebo controlled

Placebo

ACTIVE COMPARATOR

The placebo will be visually similar to pirfenidone.

Drug: Pirfenidone; Other: Placebo controlled

Interventions

Pirfenidone DRUG

This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.

Placebo; pirfenidone 2403 mg/d

Placebo controlled OTHER

This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.

Also known as: Placebo

Placebo; pirfenidone 2403 mg/d

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multidisciplinary consensus diagnosis of FHP, defined from the first instance in which a patient was informed of having FHP for at least 3 to 6 months.
• Age 18 through 80 years at randomization.
• Diagnosis of typical or compatible FHP by HRCT according to pre-specified criteria (Note: HRCT scan performed within 6 months of the start of screening may be used if it meets image acquisition guidelines):
• a. Typical FHP: Evidence of lung fibrosis (reticular abnormality and/or, traction bronchiectasis and/or, architectural distortion, and/or honeycombing) with either of the following: i. Profuse poorly defined centrilobular nodules of ground-glass opacity affecting all lung zones.
• ii. Inspiratory mosaic attenuation with the three-density sign. AND iii. Lack of features suggesting an alternative diagnosis.
• b. Compatible FHP: Evidence of lung fibrosis (as above) with any of the following: i. Patchy or diffuse ground-glass opacity. ii. Patchy, non-profuse centrilobular nodules of ground-glass attenuation iii. Mosaic attenuation and lobular air-trapping that do not meet the criteria for typical fibrotic HP.
• AND iv. Lack of features suggesting an alternative diagnosis.
• c. Indeterminate FHP: CT signs of fibrosis without other features suggestive of HP and lack of features suggesting an alternative diagnosis. These patients are required to have a known antigen exposure and BAL lymphocytosis (≥20%) or transbronchial biopsies demonstrating non-necrotizing granuloma(s) or lymphocytosis, or surgical lung histology consistent with HP.
• FHP Disease Severity and Progression
• FVC ≥40%, DLCO ≥30% based either on historical pulmonary function tests obtained in the 30 days prior to screening or on tests obtained during screening
• In the investigator's opinion, evidence of disease progression: worsening respiratory symptoms and an increased in the extent of fibrosis on HRCT or relative decline in the FVC% of at least 5%.
• Able to walk ≥100 m during the 6-minute walk test (6MWT) at Screening.
• Informed Consent and Protocol Adherence
• Able to understand and sign a written informed consent form.
• Able to understand the importance of adherence to study treatment and the study protocol and willing to follow all study requirements, including the concomitant medication restrictions, throughout the study

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 at Screening or unwilling to avoid tobacco products throughout the study
• Known explanation for the interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, pneumoconiosis.
• Clinical diagnosis of any connective tissue disease, including but not limited to scleroderma, polymyositis/dermatomyositis, and rheumatoid arthritis.
• Expected to receive a lung transplant within 6 to12 months from randomization or on a lung transplant waiting list at randomization.
• Any condition other than FHP that, in the opinion of the investigator, is likely to result in the death of the patient within 6 to12 months.
• Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone.
• Pregnancy or lactation. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence is not practiced, one of the two methods of birth control should be an oral contraceptive (e.g., oral contraceptive and a spermicide).
• History of ongoing alcohol or substance abuse.
• History of severe hepatic impairment or end-stage liver disease.
• History of end-stage renal disease requiring dialysis.
• Clinical evidence of active infection including, but not limited to, bronchitis, pneumonia, sinusitis, or urinary tract infection.
• Unstable or deteriorating cardiac disease, including but not limited to the following:
• Unstable angina pectoris or myocardial infarction.
• Congestive heart failure requiring hospitalization.

Sponsors & Collaborators

• Evans Fernandez Perez: lead
• Genentech, Inc.: collaborator

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Related Publications (3)

• Swigris JJ, Aronson K, Fernandez Perez ER. A first look at the reliability, validity and responsiveness of L-PF-35 dyspnea domain scores in fibrotic hypersensitivity pneumonitis. BMC Pulm Med. 2024 Apr 19;24(1):188. doi: 10.1186/s12890-024-02991-1.

  PMID: 38641768 DERIVED

• Fernandez Perez ER, Crooks JL, Lynch DA, Humphries SM, Koelsch TL, Swigris JJ, Solomon JJ, Mohning MP, Groshong SD, Fier K. Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety. Thorax. 2023 Nov;78(11):1097-1104. doi: 10.1136/thorax-2022-219795. Epub 2023 Apr 7.

  PMID: 37028940 DERIVED

• Fernandez Perez ER, Crooks JL, Swigris JJ, Solomon JJ, Mohning MP, Huie TJ, Koslow M, Lynch DA, Groshong SD, Fier K. Design and rationale of a randomised, double-blind trial of the efficacy and safety of pirfenidone in patients with fibrotic hypersensitivity pneumonitis. ERJ Open Res. 2021 Jun 7;7(2):00054-2021. doi: 10.1183/23120541.00054-2021. eCollection 2021 Apr.

  PMID: 34109243 DERIVED

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Evans Fernández
• Organization: National Jewish Health

fernandezevans@njheallth.org

303-388-4461

Study Officials

• Evans Fernández, MD, MS

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 31, 2016
• First Posted: November 8, 2016
• Study Start: June 5, 2017
• Primary Completion: March 2, 2021
• Study Completion: March 2, 2021
• Last Updated: January 9, 2023
• Results First Posted: January 9, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)