Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
Condition: Albinism; Inborn Errors of Metabolism; Oculocutaneous Albinism; Platelet Storage Pool Deficiency; Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Albinism; Hermanski-Pudlak Syndrome; Albinism, Oculocutaneous; Platelet Storage Pool Deficiency; Metabolism, Inborn Errors; Fibrosis
Intervention: Pirfenidone; Placebo
Intervention description: Treatment with pirfenidone 801 mg (3 pills of 267 mg each), three times daily.; Placebo (3 pills), three times daily.
Intervention MeSH terms: Pirfenidone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Albinism; Platelet Storage Pool Deficiency; Pulmonary Fibrosis; Hermansky-Pudlak Syndrome

Summary:

      Hermansky-Pudlak Syndrome (HPS) is an inherited disease that results in decreased
      pigmentation (oculocutaneous albinism), bleeding problems due to a platelet abnormality
      (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal
      accumulation of ceroid lipofuscin).

      The disease can cause poor functioning of the lungs, intestine, kidneys, or heart. The most
      serious complication of the disease is pulmonary fibrosis and typically causes death in
      patients 40 - 50 years old. The disorder is common in Puerto Rico, where many of the clinical
      research studies on the disease have been conducted. Neither the full extent of the disease
      nor the basic cause of the disease is known. There is no known treatment for HPS.

      The drug pirfenidone blocks the biochemical process of inflammation and has been reported to
      slow or reverse pulmonary fibrosis in animal systems.

      In this study researchers will select up to 40 HPS patients diagnosed with pulmonary
      fibrosis. The patients will be randomly divided into 2 groups. The patients will not know if
      they are taking pirfenidone or a placebo "sugar pill".

        1. Group one will be patients who will receive pirfenidone.

        2. Group two will be patients who will receive a placebo "sugar pill"

      The major outcome measurement of the therapy will be a change in the lung function (forced
      vital capacity). The study will be stopped if one therapy proves to be more effective than
      the other.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

        For the portion of the protocol involving continuations of pirfenidone treatment, the
        criteria are simply previous enrollment in 97-HG-0085.

        For enrollment in the new clinical trial, the inclusion criteria involve enrollment in
        protocol 95-HG-0193, "Clinical and Basic Investigations into Hermansky-Pudlak Syndrome".
        This itself requires a diagnosis of HPS based upon molecular grounds or the electron
        microscopic demonstration of deficiency of platelet dense bodies. In addition, for protocol
        97-HG-0085, patients must:

          -  Be over 18 years of age.

          -  Have an FVC greater than 50 percent and less than or equal to 85 percent of predicted
             OR a hemoglobin-corrected DL(co) greater than 35 percent and less than or equal to 80
             percent of predicted, with no evidence of a pulmonary embolism.

          -  Have evidence of reduced exercise tolerance lasting longer than one week on either the
             St. George's Hospital Respiratory Questionnaire or the Dyspnea Perception Scale.

          -  FEV(1)/FVC greater than 80 percent of predicted after bronchodilators.

          -  No evidence of improvement in pulmonary fibrosis within the past year defined as an
             FVC increased by 10 percent or a DL(co) increased by 15 percent.

          -  Distance walked greater than or equal to 150 meters (492 feet) with oxygen saturation
             greater than or equal to 83 percent on less than or equal to 6 L/min. of oxygen during
             the 6-Minute Walk Test (6MWT).

          -  Be available, willing, and able to come to the NIH Clinical Center for admission every
             4 months for three years.

        EXCLUSION CRITERIA

          -  History of clinically significant environmental exposure known to cause pulmonary
             fibrosis (including but not limited to drugs, asbestos, beryllium, radiation, domestic
             birds).

          -  An explanation for interstitial lung disease other than HPS, including but not limited
             to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans
             organizing pneumonia, cancer.

          -  Diagnosis of any connective tissue disease including but not limited to scleroderma,
             systemic lupus erythematosus, rheumatoid arthritis.

          -  Listing on a lung transplantation waiting list.

          -  Pregnancy or lactation

          -  Cigarette smoking in the past 6 months

          -  History of ethanol abuse or recreational drug use in the past two years

          -  History of human immunodeficiency virus (HIV) or chronic viral hepatitis infection

          -  Chronic use of high-dose steroids (greater than 10 mg prednisone/day)

          -  Prior use of pirfenidone

          -  Use of any of the following within 28 days of enrollment: investigational therapy,
             cytotoxic/immunosuppressive agents other than corticosteroids (including but not
             limited to azathioprine, cyclosphosphamide, methotrexate, cyclosporine); cytokine
             modulators (including but not limited to etanercept and infliximab); therapies
             targeted to treat pulmonary fibrosis (including but not limited to D-penicillamine,
             colchicine, interferon gamma-1b, bosentan, N-acetylcysteine

          -  Any severe medical complication including but not be limited to uncontrolled seizures,
             repeated transient ischemic attacks, abnormal mental status, severe ataxia,
             uncontrolled migraine headaches, diplopia, repeated episodes of syncope, untreated
             clinical depression, recent myocardial infarction (past 6 months), unstable angina,
             clinically relevant arrhythmias, uncontrolled hypotension or hypertension (systolic
             blood pressure less than 80 or greater than 180 mm Hg), myocarditis, hepatomegaly
             (liver greater than 3 cm below the right costal margin), renal glomerular impairment
             (creatinine clearance less than 35 ml/min/1.73 m2, pancreatitis, toxic thyroiditis,
             malignancy (except basal cell carcinoma)

          -  Medications with a high frequency of life threatening side effects

          -  Significant laboratory abnormalities, including but not limited to serum potassium
             less than 3.0 or greater than 5.4 mEq/L, SGPT greater than 100 U/L, CK greater than
             700 U/L, hemoglobin less than 9.0 g/dL, platelets less than 70 k/mm3, leucocyte count
             less than 2.0 k/microliter, or cholesterol greater than 400 mg/dL.

          -  For women of child bearing age, failure to have an effective method of birth control.