The Safety and Tolerability of Pirfenidone for BOS After HCT

NCT03315741 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-43319VAR0158
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, non-randomized, single-arm, open label, single center clinical trial to determine the tolerability and safety of pirfenidone in patients with BOS associated with lung GVHD after hematopoietic cell transplant.

Conditions

Bronchiolitis Obliterans; Graft Vs Host Disease

Keywords

Bronchiolitis obliterans syndrome

Outcome Measures

Primary Outcomes (1)

• The number of participants that do not require a reduction in drug dose for more than 21 days due to adverse events.

  We will count the number of participants that do not require a reduction in drug dose of more than 21, non-continuous days due to adverse events. Tolerability will be assessed during continuous treatment. If the medication dosage increase results in the reoccurrence of a moderate adverse event or serious adverse event, lasting more than 21 days, then the event would be defined as "not tolerated". If adverse events resolve before 21 days, then participants will attempt to again up-titrate the Pirfenidone dose, as tolerated. If at least 25% of participants tolerate the drug, then investigators will deem that this study demonstrates adequate tolerability to proceed to a larger trial to examine drug efficacy.

  52 weeks

Secondary Outcomes (14)

• The number of participants that permanently discontinue drug due to adverse events.

  52 weeks

• The number of participants that temporarily discontinue drug due to adverse events.

  52 week

• The number of patients that experience treatment-emergent adverse events

  56 week

• The number of patients that experience treatment-emergent serious adverse events (SAEs)

  56 week

• The number of patients that experience treatment-emergent deaths during the study period and for 28 days after the last dose of study treatment.

  56 week

Other Outcomes (8)

• Pulmonary function testing: spirometric change from baseline to week 52.

  52 week

• Pulmonary function testing: diffusion capacity for carbon monoxide (DLCO) change from baseline to week 52.

  52 week

• Change from Baseline to Week 52 in % air trapping as measured by volumetric CT thorax with lung density analysis

  52 week

Study Arms (1)

Patient centered approach

EXPERIMENTAL

Drug titration of maximum dose over 3-8 weeks

Drug: Pirfenidone 267 MG [Esbriet]

Interventions

Pirfenidone 267 MG [Esbriet] DRUG

Tolerability of drug

Patient centered approach

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years at randomization
• Clinical symptoms (e.g., dyspnea or cough) consistent with BOS of ≥ 2 months duration
• Presence of cGVHD in an organ other than lung
• Subjects must have had recent pulmonary function test (PFTs) measured for at least 3 months prior to study enrollment that show:
• A decrease in %FVC and/or %FEV1 ≥ 20% at Screening compared with pre-transplant baseline.
• Bronchodilator response on PFT testing that results in an FEV1 \< 75%
• Diagnosis of BOS by one of the following criteria:
• Transbronchial or surgical lung biopsy demonstrating the obliterative bronchiolitis lesion
• Volumetric CT scan with lung density analysis with ≥ 28% air trapping (1).
• NIH-based PFT criteria for the diagnosis of BOS: FEV1/FVC \<0.7 and FEV1 \< 75%
• Evidence of clinical improvement after treatment for BOS has been initiated.
• No features supporting an alternative diagnosis by transbronchial biopsy, bronchoalveolar lavage (BAL), surgical lung biopsy, culture and non-culture based data, if performed
• Adequate organ and marrow function including: liver function as defined by a total bilirubin below the upper limit of normal (ULN), excluding patients with Gilbert's syndrome; AST/SGOT or ALT/SGPT \< 3 x ULN; alkaline phosphatase \< 2.5 x ULN; renal function as defined by a CrCl \> 30 mL/min, calculated using the Cockcroft-Gault formula; cardiac electrophysiologic stability as defined by an electrocardiogram (ECG) with a QTc interval \< 500 msec at Screening; and bone marrow function as defined by a white blood cell count \> 3 K/µL, an absolute neutrophil count \> 15 K/µL and a platelet count \> 20 K/µL
• Life expectancy \> 6 months
• Participants must be able to understand and sign a written informed consent form and understand the importance of adherence to study treatment and protocol. In addition, participants must demonstrate a willingness to follow all study requirements, including the concomitant medication restrictions, throughout the study

You may not qualify if:

• Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone e.g., presence of active GVHD of the gastrointestinal tract as manifested by rising liver function tests (LFTs) prior to initiation of study treatment
• Uncontrolled infection
• Major surgery within the past 2 months
• The use of another investigational drug within the previous 30 days.
• Inability to attend scheduled clinic visits
• Inability to perform pulmonary function testing
• Significant clinical change in health in the past 30 days
• Body mass index (BMI) \< 17.5
• Life expectancy \< 6 months due to any condition other than BOS that, in the opinion of the investigator, is likely to result in the death of the patient.
• History of unstable or deteriorating cardiac or pulmonary disease (other than BOS) within the previous 6 months, including but not limited to the following:
• Unstable angina pectoris or myocardial infarction
• Congestive heart failure requiring hospitalization
• Uncontrolled clinically significant arrhythmias
• Pregnancy or lactation.
• Family or personal history of long QT syndrome

Sponsors & Collaborators

• Stanford University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

Related Publications (2)

• Sharifi H, Moss CT, Musa Z, Bell A, O'Donnell C, Borges CH, Matthaiou EI, Johnston L, Galban CJ, Sheshadri A, Yanik G, Cheng GS, Hsu JL. Pirfenidone for the treatment of bronchiolitis obliterans syndrome related to chronic graft-versus-host disease. Blood Adv. 2025 Oct 14;9(19):5024-5037. doi: 10.1182/bloodadvances.2025016122.

  PMID: 40554417 DERIVED

• Matthaiou EI, Sharifi H, O'Donnell C, Chiu W, Owyang C, Chatterjee P, Turk I, Johnston L, Brondstetter T, Morris K, Cheng GS, Hsu JL. The safety and tolerability of pirfenidone for bronchiolitis obliterans syndrome after hematopoietic cell transplant (STOP-BOS) trial. Bone Marrow Transplant. 2022 Aug;57(8):1319-1326. doi: 10.1038/s41409-022-01716-4. Epub 2022 May 31.

  PMID: 35641662 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases; Organizing Pneumonia

Study Officials

• Joe L Hsu, MD, MPH

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 1, non-randomized, single arm, open label, single center clinical trial to determine the tolerability and safety of pirfenidone in patients with BOS associated with lung GVHD after hematopoietic cell transplant (HCT). Approximately 30 patients will be enrolled. All patients will follow the 'patient-centered' drug titration approach.

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 20, 2017
• Study Start: March 1, 2018
• Primary Completion: February 27, 2022
• Study Completion: April 27, 2022
• Last Updated: June 13, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)