The Safety and Tolerability of Pirfenidone for BOS After HCT

• Register: ClinicalTrials.gov
• Last refreshed on: 20 June 2022
• Main ID: NCT03315741
• Date of registration: 05/10/2017
• Prospective Registration: Yes
• Primary sponsor: Stanford University
• Public title: The Safety and Tolerability of Pirfenidone for BOS After HCT STOP-BOS
• Scientific title: The Safety and Tolerability of Pirfenidone for Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation
• Date of first enrolment: March 1, 2018
• Target sample size: 30
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03315741
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Joe L Hsu, MD, MPH
• Affiliation: Stanford University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age > 18 years at randomization

2. Clinical symptoms (e.g., dyspnea or cough) consistent with BOS of = 2 months duration

3. Presence of cGVHD in an organ other than lung

4. Subjects must have had recent pulmonary function test (PFTs) measured for at least 3
months prior to study enrollment that show:

1. A decrease in %FVC and/or %FEV1 = 20% at Screening compared with pre-transplant
baseline.

2. Bronchodilator response on PFT testing that results in an FEV1 < 75%

5. Diagnosis of BOS by one of the following criteria:

1. Transbronchial or surgical lung biopsy demonstrating the obliterative
bronchiolitis lesion

2. Volumetric CT scan with lung density analysis with = 28% air trapping (1).

3. NIH-based PFT criteria for the diagnosis of BOS: FEV1/FVC <0.7 and FEV1 < 75%

4. Evidence of clinical improvement after treatment for BOS has been initiated.

6. No features supporting an alternative diagnosis by transbronchial biopsy,
bronchoalveolar lavage (BAL), surgical lung biopsy, culture and non-culture based
data, if performed

7. 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

8. Life expectancy > 6 months

9. 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

Exclusion Criteria:

1. 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

2. Uncontrolled infection

3. Major surgery within the past 2 months

4. The use of another investigational drug within the previous 30 days.

5. Inability to attend scheduled clinic visits

6. Inability to perform pulmonary function testing

7. Significant clinical change in health in the past 30 days

8. Body mass index (BMI) < 17.5

9. 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.

10. History of unstable or deteriorating cardiac or pulmonary disease (other than BOS)
within the previous 6 months, including but not limited to the following:

1. Unstable angina pectoris or myocardial infarction

2. Congestive heart failure requiring hospitalization

3. Uncontrolled clinically significant arrhythmias

11. Pregnancy or lactation.

12. Family or personal history of long QT syndrome

13. Investigational therapy, defined as any drug that has not been approved for marketing
for any indication in cGVHD will be restricted from the study

14. The following medications may significantly increase the level of Pirfenidone and
should not be taken concurrently including: fluvoxamine, ciprofloxacin > 500mg twice
daily, systemically administered aminolevulinic acid, vemurafenib and enoxacin. Any
other strong inhibitors of P450 isoenzymes CYP1A2, CYP2C9, 2C19, 2D6, and 2E1 should
be avoided. Participants that cannot take alternative medications to those listed
above will be excluded from this study.

Laboratory Exclusions

1. Any of the following LFT criteria above specified limits: total bilirubin above the
upper limit of normal (ULN), excluding patients with Gilbert's syndrome; aspartate or
alanine aminotransferase (AST/SGOT or ALT/SGPT) >3 × ULN; alkaline phosphatase >2.5 ×
ULN

2. Creatinine clearance (CrCl) <30 mL/min, calculated using the Cockcroft-Gault formula

3. Electrocardiogram (ECG) with a QTc interval >500 msec at Screening

Medication Exclusions

1. Prior use of pirfenidone or known hypersensitivity to any of the components of study
treatment.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Bronchiolitis Obliterans

Graft Vs Host Disease

Intervention(s)

Drug: Pirfenidone 267 MG [Esbriet]

Primary Outcome(s)

The number of participants that do not require a reduction in drug dose for more than 21 days due to adverse events. [Time Frame: 52 weeks]

Secondary Outcome(s)

The number of patients that experience treatment-emergent changes in the corrected QT-interval on electrocardiogram. [Time Frame: 52 week]

The number of participants that temporarily discontinue drug due to adverse events. [Time Frame: 52 week]

The number of patients that experience treatment-emergent adverse events [Time Frame: 56 week]

Chronic GVHD assessment [Time Frame: 56 week]

The number of patients that experience treatment-emergent changes in liver function testing. [Time Frame: 52 week]

The number of patients that experience treatment-emergent changes in serum chemistries panel. [Time Frame: 52 week]

The number of patients that experience treatment-emergent serious adverse events (SAEs) [Time Frame: 56 week]

The number of patients that experience treatment-emergent changes in complete blood counts. [Time Frame: 52 week]

Body mass index [Time Frame: 52 week]

Oxygen saturation [Time Frame: 52 week]

The number of participants that permanently discontinue drug due to adverse events. [Time Frame: 52 weeks]

The number of patients that experience treatment-emergent deaths during the study period and for 28 days after the last dose of study treatment. [Time Frame: 56 week]

All-cause mortality [Time Frame: 56 week]

Heart rate [Time Frame: 52 week]

Secondary ID(s)

IRB-43319

VAR0158

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genentech, Inc.