Pirfenidone for Restrictive Chronic Lung Allograft Dysfunction

Summary

Despite advances in lung transplantation, the median survival remains only 55% at 5 years. The main limitation to long term survival is the development of chronic lung allograft dysfunction. In approximately 30% of cases, chronic lung allograft dysfunction has a restrictive phenotype (RCLAD) characterized by fibrosis with rapid progression to respiratory failure. Approximately 60% of patients with RCLAD die within one year, as currently there are no therapies available.

RCLAD, like Idiopathic Pulmonary Fibrosis (IPF), is characterized by fibroblast proliferation, extracellular matrix deposition, and architectural distortion leading to progressive lung scarring and death. Given their similarities, there is keen interest in the international transplant community to investigate whether the anti-fibrotic drug pirfenidone can slow the progression of RCLAD as it does of IPF. Pirfenidone has been proved to be safe and effective in patients with IPF, and is approved by the Food and Drug Administration.

This protocol will evaluate the safety and tolerability of pirfenidone in lung transplant recipients with RCLAD. Transplant recipients take carefully adjusted immunosuppressive medications for life to prevent rejection of the allograft. Current literature suggests the dose of tacrolimus, the main anti-rejection drug, may need to be adjusted when taken in combination with pirfenidone. The investigators will assess the side effects of pirfenidone in combination with the immunosuppressive regimen and determine the magnitude of the adjustment in tacrolimus dose. The results of this pilot study will provide the foundation for a multicenter randomized control trial to evaluate the efficacy of pirfenidone in slowing the progression of RCLAD.

Conditions

• Restrictive Chronic Lung Allograft Dysfunction
• Lung Transplant Rejection

Interventions

DRUG

Pirfenidone

Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.

Sponsors & Collaborators

• Genentech, Inc.

  collaborator INDUSTRY

• University of California, San Francisco

  lead OTHER

Principal Investigators

• Aida A Venado Estrada, MD · University of California, San Francisco

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-07

Primary Completion

2021-10-28

Completion

2021-10-28

FDA Drug

Yes

Countries

• United States

Study Locations