Clinical trial: Efficacy and Safety of Pirfenidone Treatment in HPS-ILD (NCT04193592)

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
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 75 Years

Patient description (medical language): A 4-year-old boy comes to the office for the follow up of his confirmed oculocutaneous albinism.  The patient was born at 38 weeks gestation with no complications.  Vital signs are normal.  Weight and height are at the 50th percentile.  On examination, iris transillumination is present, and there are no apparent foveae on funduscopic examination.  Optic nerves are small and gray.  All the hairs including eyebrows and lashes are white.

Patient description (patient's own words): I brought my four-year-old son to his follow-up consultation for his albinism. All his hair is white, even lashes and eyebrows. My baby was born at 38 weeks pregnant with no complications whatsoever. During the consultations his vitals were normal and now his weight and height are at the 50th percentile. The doctor did an eye exam and it seems that his iris has a kind of transillumination, and there are no foveae. The doctor told me that his optic nerves are small and gray.

Does the patient match the trial criteria? Contradiction