European Trial of Pirfenidone in BOS, A European Multi-center Study

NCT02262299 | Completed Phase 2 DMC

• 1 other identifier: RH-HJE-2014-09
• Study Type: interventional
• Target: 90
• Locations: 7 countries
• Sites: 9

Brief Summary

A European multi-centre, randomised, double-blind placebo-controlled trial of Pirfenidone in bronchiolitis-obliterans-syndrome grade 1-3 in lung transplant recipients. Randomized double blinded, placebo controlled study. Eligible patients are to be randomized in a 1:1 ratio to receive either Pirfenidone 2403 mg/d or the matching placebo treatment for 6 months. Primary objective To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.

Conditions

Disorder Related to Lung Transplantation; CLAD, Bronchiolitis Obliterans

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.

  6 months

Secondary Outcomes (11)

• - Categorical percentage change in FEV1

  6 months

• - Change in Forced Vital Capacity (FVC)

  6 months

• - Change in Total Lung Capacity (TLC)

  6 months

• - Change in FEV1/FVC ratio

  6 months

• - Number of patients with treatment failure

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Receive placebo tablets

Drug: Placebo

Pirfenidone

ACTIVE COMPARATOR

Upon enrollment, subjects will be randomized to either the treatment group (Pirfenidone) or to the placebo group (1:1 ratio). The trial medication will be administered as 267-mg oral capsules and titrated to a maintenance dose of 2403 mg/d (3 capsules TID, for a total of 9 capsules/day).

Drug: Pirfenidone

Interventions

Pirfenidone DRUG

Receive tablets with pirfenidone

Also known as: Esbriet

Pirfenidone

Placebo DRUG

Recieve tablets with placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients \>18 years of age
• Azithromycin therapy for at least 4 weeks prior to study start, with an Azithromycin dose of minimum 250 mg/day at least 3 times per week as this is considered standard therapy for bronchiolitis obliterans syndrome.
• Double lung transplantation is required.
• Patients must be at least 6 months after transplantation and must have documented post-transplant baseline value of FEV1 (mean of the 2 highest values measured at least 3 weeks apart according to ISHLT criteria).
• Patients must have BOS grade 1 to BOS grade 3.
• Patients must have documented progressive disease as demonstrated by all of the following criteria:
• Patients must have at least 3 FEV1-measurements in the last 6 months, each at least 3 weeks apart
• a total decline of at least 200ml in FEV1 i
• a decline of at least 50 ml in the last two measurements

You may not qualify if:

• Patients with lung redo transplantation, combined transplantation (including heart and lung transplantation) or single lung recipients.
• Patients with any severe comorbidity complicating BOS which might determine the prognosis and functional level of the patient (e.g. invasive aspergillosis, active malignant disease) within the last 12 months.
• FEV1 decline related to other non BOS causes (eg pneumothorax, bronchial stenosis, effusion, etc.)
• Patients who have developed BOS grade 3.
• Patients who on Thorax CT at entry demonstrate new significant findings which are not compatible with BOS like interstitial fibrosis, consolidation, appearances suggesting Restrictive Allograft Syndrome (RAS) and acute pulmonary infection as cause of decline in lung function.
• Documented acute perivascular rejection higher than grade A1 or findings compatible with antibody mediated rejection
• 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).
• Renal insufficiency (Creatinine clearance \<30 ml/min calculated by the CKD-Epi formula.
• Any of the following liver test criteria above the specified limit:
• Total bilirubin above the upper limit of the normal range (ULN), except in patients with predominantly unconjugated hyperbilirubinemia (e.g., Gilbert's syndrome)
• Aspartate or alanine aminotransferase (AST or ALT) \>3 × ULN
• Known allergy or hypersensitivity to Pirfenidone
• Ongoing use or expected use of any of the following therapies:
• Strong inhibitors of CYP1A2 (e.g. fluvoxamine or enoxacin)
• Moderate inhibitors of CYP1A2 (e.g. mexiletine, thiabendazole, or phenylpropanolamine \[Note: ciprofloxacin will be allowed only at doses ≤500 mg BID\])

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (9)

University Hospital Gasthuisberg, Katholike Universiteit Leuven

Leuven, 300, Belgium

Location

Rigshospitalet, Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

University Hospital Essen, Department of Pneumonology

Essen, 45239, Germany

Location

Medizinische Hochschule Hannover, Klinik für Pneumonologie

Hanover, 30625, Germany

Location

Klinikum Grosshadern, Division of Pulmonary Diseases

Munich, 81377, Germany

Location

Groningen University Medical Center, Lung Transplant Team

Groningen, 9700, Netherlands

Location

Rikshospitalet, National University Hospital

Oslo, 0424, Norway

Location

Sahlgrenska University Hospital, Department of respiratory diseases

Gothenburg, 41345, Sweden

Location

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

Location

Related Publications (1)

• Perch M, Corris P, Lordan J, Bessa V, Magnusson J, Verleden GM, Vos R, Kneidinger N, Leuckfeld I, Verschuuren E, Gottlieb J. A European multi-center, randomized controlled trial of Pirfenidone in bronchiolitis obliterans syndrome after bilateral lung transplantation. Eur Respir J. 2025 Nov 13:2402154. doi: 10.1183/13993003.02154-2024. Online ahead of print.

  PMID: 41232942 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Study Officials

• Michael Perch, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

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: Medical Director Danish National Lung Transplant Program

Study Record Dates

• First Submitted: September 21, 2014
• First Posted: October 13, 2014
• Study Start: May 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

NL (1); BE (1); DE (3); NO (1); GB (1); SE (1); DK (1)