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Efficacy and Safety of Pirfenidone Treatment in HPS-ILD (PEARL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04193592
Recruitment Status : Not yet recruiting
First Posted : December 10, 2019
Last Update Posted : December 10, 2019
Genentech, Inc.
Information provided by (Responsible Party):
Jesse Roman, Thomas Jefferson University

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.

Condition or disease Intervention/treatment Phase
Hermansky Pudlak Syndrome Interstitial Lung Disease Drug: Pirfenidone Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: open label drug
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pirfenidone in the Treatment of Hermansky Pudlak Syndrome (HPS) - Related Interstitial Lung Disease (ILD)
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Arm Intervention/treatment
Experimental: 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.
Drug: 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.
Other Name: Esbriet

Primary Outcome Measures :
  1. Change in Forced Vital Capacity (FVC) [ Time Frame: baseline, 6 months, 12 months ]
    The incidence of decline in percent predicted FVC of 10 % or greater from baseline measured at 6 and 12 months

Secondary Outcome Measures :
  1. Change in Forced Vital Capacity (FVC) [ Time Frame: week 52 ]
    1. The Incidence of decline from baseline in percent predicted FVC of 10% or greater during the 52 week treatment period.

  2. Change in Diffusion Capacity (DLCO) [ Time Frame: week 52 ]
    2. The Incidence of decline from baseline in percent predicted DLCO of 15% or greater during the 52 week treatment period.

  3. Incidence of Treatment Emergent Adverse Events [ Time Frame: week 52 ]
    3. The number of participants with and number of treatment emergent adverse events reported by the participant will be collected.

  4. Incidence of Treatment Emergent Serious Adverse Events [ Time Frame: week 52 ]
    4. The number of participants with and number of treatment-emergent serious adverse events reported by the participants will be collected.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04193592

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Contact: Tamra Perez, BSN 1-215-955-9181
Contact: Melissa McCarey 267 503-7417

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United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Contact: Tamra Perez    215-955-9181   
Principal Investigator: Jesse Roman, MD         
Puerto Rico
Mayaguez Medical Center
Mayaguez, Puerto Rico, 00680
Contact: Rosa Roman, MD    7874676080      
Principal Investigator: Rosa Roman, MD         
Sponsors and Collaborators
Jesse Roman
Genentech, Inc.
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Principal Investigator: Jesse Roman, MD Thomas Jefferson University
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Responsible Party: Jesse Roman, Professor of Medicine, Thomas Jefferson University Identifier: NCT04193592    
Other Study ID Numbers: 14172/2019
First Posted: December 10, 2019    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Jesse Roman, Thomas Jefferson University:
patient reported outcomes
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Interstitial
Hermanski-Pudlak Syndrome
Pathologic Processes
Respiratory Tract Diseases
Albinism, Oculocutaneous
Eye Diseases, Hereditary
Eye Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Platelet Storage Pool Deficiency
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Skin Diseases, Genetic
Pigmentation Disorders
Skin Diseases
Metabolic Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs