Efficacy and Safety of Pirfenidone Treatment in HPS-ILD

NCT ID: NCT04193592

Last Updated: 2019-12-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-01
• Study Completion Date: 2022-12-31

Brief Summary

This research study will explore the safety and efficacy of the drug, pirfenidone, in patients with a diagnosis of Hermansky-Pudlak Syndrome (HPS) who have an associated interstitial lung disease (ILD) over a planned period of 56 weeks.

Detailed Description

An open-label clinical study designed to evaluate the efficacy and safety of administering pirfeniodne for 52 weeks to subjects with HPS-ILD. Patients meeting the eligibility criteria without contraindications for the study will be provided pirfenidone 2403 mg/day. Efficacy will be evaluated through interval testing of pulmonary function tests, patient reported outcomes, adverse events and survival. Safety will be assessed by determining adverse events, hospitalizations, and all-cause mortality.

Conditions

Hermansky Pudlak Syndrome; Interstitial Lung Disease

Keywords

safety; efficacy; patient reported outcomes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral Pirfenidone 2403 mg per day

Enrolled subjects will receive oral pirfenidone 801 mg taken three times a day. Pirfenidone will be supplied in 267 mg capsules.

Group Type: EXPERIMENTAL

Pirfenidone

Intervention Type: DRUG

Pirfenidone will be titrated over 14 days, as tolerated, to the full dose of 2403 mg per day, as follows: Days 1 - 7: one capsule TID; Days 8 - 14: two capsules TID; Days 15 to week 52: three capsules TID. Dose may be reduced to manage an adverse event.

Interventions

Pirfenidone

Pirfenidone will be titrated over 14 days, as tolerated, to the full dose of 2403 mg per day, as follows: Days 1 - 7: one capsule TID; Days 8 - 14: two capsules TID; Days 15 to week 52: three capsules TID. Dose may be reduced to manage an adverse event.

Intervention Type: DRUG

Other Intervention Names

Esbriet

Eligibility Criteria

Inclusion Criteria

• Probable or definite diagnosis of HPS based on confirmed genetic mutation or clinical picture characterized by oculo-cutaneous albinism, bleeding disorder, and possible colitis and ILD.
• Diagnosis of ILD supported by clinically indicated HRCT prior to Screening, and presence of fibrotic abnormality affecting more than 5% of the lung parenchyma, with or without traction bronchiectasis or honeycombing, on Screening
• No features supporting an alternative diagnosis (e.g., infection)
• Change in pre-bronchodilator FVC (measured in liters) between Screening (Visit 1) and

Baseline (Visit 2) must be a < 10% relative difference, calculated as:

100%*[absolute value (Screening FVC - Baseline FVC)/Screening FVC

• Stable dose (at least three months at the time of Screening) of corticosteroids.
• No cytotoxic, immunosuppresive agents, cytokine-modulating, or receptor antagonists agents are allowed (including but not limited to azathioprine, cyclophosphamide, cyclosporine, etanercept, iloprost, infliximab, methotrexate, mycophenolate mofetil, nintedanib, tacrolimus, tetrathiomolybdate, TNF-α inhibitors, rituximab, abatacept, tofacitintib, tociluzimab).
• Able to understand and sign a written informed consent form

Exclusion Criteria

• Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator
• Cigarette smoking within 3 months of Screening or unwilling to avoid tobacco products throughout the study
• History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds
• Concurrent presence of other interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer
• Concurrent presence of other pleuropulmonary manifestations inconsistent with HPS- ILD
• Presence of pleural effusion occupying more than 10% of the hemithorax on Screening HRCT
• Clinical diagnosis of a connective tissue disease or overlap syndrome (including but not limited to rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus)
• Coexistent clinically significant COPD/emphysema or asthma in the opinion of the site principle investigator
• Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis
• Any history of malignancy diagnosed within 5 years of screening, other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or low grade cervical carcinoma in situ.
• History of severe hepatic impairment or end-stage liver disease
• History of end-stage renal disease requiring dialysis
• History of unstable or deteriorating cardiac or disease, myocardial infarction within the previous year, heart failure within the last 3 years, or cardiac arrhythmia requiring drug therapy
• Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, during the 52 weeks of treatment.

1. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).

2. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

3. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:

1. With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 118 days after the last dose of pirfenidone.

2. Men must refrain from donating sperm during this same period.

• Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site including pirfenidone, at the time of Screening
• History of alcohol or substance abuse in the past 2 years, at the time of Screening
• Family or personal history of long QT syndrome
• Any of the following liver function test criteria above specified limits:

1. 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 QTcB interval >500 msec at Screening

• Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment
• Use of any of the following therapies within 28 days before Screening:

1. Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site

2. Fluvoxamine

3. Sildenafil (daily use). Note: intermittent use for erectile dysfunction is allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Jesse Roman

OTHER

Sponsor Role: lead

Responsible Party

Jesse Roman

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jesse Roman, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Mayaguez Medical Center

Mayagüez, , Puerto Rico

Countries

United States; Puerto Rico

Central Contacts

Tamra Perez, BSN

Role: CONTACT

Phone: 1-215-955-9181

Email: tamra.perez@jefferson.edu

Melissa McCarey

Role: CONTACT

Phone: 267 503-7417

Email: Melissa.McCarey@jefferson.edu

Facility Contacts

Tamra Perez

Role: primary

Rosa Roman, MD

Role: primary

Other Identifiers

14172/2019

Identifier Type: -

Identifier Source: org_study_id