Studying the Treatment Effect of Pirfenidone in Chronic Lung Allograft Dysfunction (STOP-CLAD)

NCT03473340 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: HUM00131610
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Greater than 50% of lung transplant recipients show signs of chronic lung allograft dysfunction (CLAD) by 5 years post-transplantation.Therapies to prevent or slow CLAD are lacking. Anti-fibrotic therapies may offer an avenue to prevent progression of CLAD and prolong allograft survival. This study investigates if Pirfenidone therapy will stabilize lung function decline and slow progression of Functional small airways disease (fSAD) in lung transplant recipients with CLAD.

Conditions

Disorder Related to Lung Transplantation; Chronic Lung Allograft Dysfunction

Keywords

CLAD; Chronic Rejection; Lung Transplant

Outcome Measures

Primary Outcomes (1)

• Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping

  Evaluate if pirfenidone compared to placebo will stabilize progression of fSAD by comparison of inspiratory and expiratory high resolution computed tomography (HRCT) images through co-registration to provide quantitative measures of fSAD.

  Baseline, 24 weeks

Secondary Outcomes (4)

• Change in Forced Expiratory Volume 1 Over 24 Weeks (FEV1)

  Baseline, 24 weeks

• Change in Forced Vital Capacity (FVC) Over 24 Weeks

  Baseline, 24 weeks

• Number of Adverse Events Related to Study Treatment

  28 weeks

• Number of Subjects With Treatment Intolerance

  24 weeks

Study Arms (2)

Pirfenidone Capsule

EXPERIMENTAL

Method of Administration: Oral (capsule) Dosing: * Days 1 through 7, 267 mg three times daily; * Days 8 through 14, 534 mg three times daily; * Days 15 through end of treatment (24 weeks), 801 mg three times daily

Drug: Pirfenidone Capsule

Placebo Capsule

PLACEBO COMPARATOR

Method of Administration: Oral (capsule) Dosing: * Days 1 through 7, 267 mg three times daily; * Days 8 through 14, 534 mg three times daily; * Days 15 through end of treatment (24 weeks), 801 mg three times daily

Drug: Placebo Capsule

Interventions

Pirfenidone Capsule DRUG

Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks

Also known as: Esbriet

Pirfenidone Capsule

Placebo Capsule DRUG

Dosing: * Days 1 through 7, 267 mg three times daily; * Days 8 through 14, 534 mg three times daily; * Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks

Also known as: Placebo

Placebo Capsule

Eligibility Criteria

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

You may qualify if:

• Lung transplant recipients 18 years of age or older
• Greater than 6 months after single or bilateral lung transplantation
• Baseline FEV1 and FVC values (mean of two highest value measured 3 weeks apart) \> 50% predicted (to assure viable graft)
• Diagnosis of CLAD (two consecutive spirometric values of FEV1 alone or both FEV1 and FVC \< 80% of baseline)

You may not qualify if:

• Acute Rejection (AR) diagnosis by biopsy in the 28 days prior to enrollment
• Treatment with pulse steroids, Anti-thymocyte Globulin (ATG), extracorporeal photopheresis (ECP), plasmapheresis, or Immunoglobulin therapy aimed at CLAD within the 28 days prior to enrollment
• If the subject is receiving chronic Azithromycin therapy, the dose must be stable for the 28 days prior to enrollment
• Presence of active pulmonary infection at the time of enrollment as determined by an investigator in consultation with the treating pulmonologist
• Diagnosis of bronchial stenosis either a) requiring stenting, or b) thought to be responsible for the spirometric decline by principal investigator
• Abnormal liver function tests (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN), Alkaline phosphatase \> 2.5 x ULN, total bilirubin \> ULN) or known cirrhosis (\>2 times upper limit of normal of AST/ALT/AP)
• Total white blood cell (WBC) \< 3.0 K/uL
• Moderate to Severe Renal insufficiency (CrCl \<15 mL/min calculated by the Cockcroft-Gault equation)
• Use of any medication known to cause significant interactions with pirfenidone (strong CYP1A2 inhibitors such as Fluvoxamine or Enoxacin or inducers)
• Pregnancy or lactation. Women of child-bearing potential will have a pregnancy test at enrollment and must agree to maintain highly effective contraception with two methods of birth control from the date of consent through the end of the study.
• Tobacco use within 6 months
• History of alcohol abuse in the past 1 year as determined by the treating pulmonologist
• Any condition other than CLAD that will likely result in death in the next 1 year
• Any condition in the judgement of the principal investigator that would preclude participation in this study
• EKG with QTc interval \> 500 msec at screening

Sponsors & Collaborators

• University of Michigan: lead
• Genentech, Inc.: collaborator

Study Sites (1)

The University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Interventions

pirfenidone

Results Point of Contact

• Title: VIbha Lama
• Organization: University of Michigan

vlama@med.umich.edu

734-936-5010

Study Officials

• Vibha Lama, MD

  University of Michigan

  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: PRINCIPAL INVESTIGATOR
• PI Title: Henry Sewall Research Professor of Pulmonary and Critical Care Medicine and Professor of Internal Medicine, Medical School

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 22, 2018
• Study Start: April 27, 2018
• Primary Completion: July 23, 2021
• Study Completion: August 20, 2021
• Last Updated: August 17, 2022
• Results First Posted: August 17, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)