Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome

NCT00001596 | Completed Phase 2 Results DMC

• 2 other identifiers: 97008597-HG-0085
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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. 1.Group one will be patients who will receive pirfenidone.
2. 2.Group two will be patients who will receive a placebo "sugar pill"

Conditions

Albinism; Inborn Errors of Metabolism; Oculocutaneous Albinism; Platelet Storage Pool Deficiency; Pulmonary Fibrosis

Keywords

Albinism; Platelet Storage Pool Deficiency; Pulmonary Fibrosis; Hermansky-Pudlak Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in Forced Vital Capacity (36 Months)

  Change from baseline in the Forced Vital Capacity (FVC) measurement at 36 months. FVC is the volume of air that can be forcibly blown out from the lungs after full inspiration. FVC is recorded as the percentage of predicted volume (predicted FVC volume is calculated based on subject's height, age, sex, and weight).

  Measured at baseline and 36 months

Secondary Outcomes (7)

• Change in Forced Vital Capacity (12 Months)

  Measured at baseline and 12 months

• Change in Total Lung Capacity (36 Months)

  Measured at baseline and 36 months

• Change in Total Lung Capacity (12 Months)

  Measured at baseline and 12 months

• Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (36 Months)

  Measured at baseline and 36 months

• Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (12 Months)

  Measured at baseline and 12 months

Study Arms (2)

Pirfenidone

ACTIVE COMPARATOR

Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.

Drug: Pirfenidone

Placebo

PLACEBO COMPARATOR

Subjects received placebo (3 pills), three times daily.

Drug: Placebo

Interventions

Pirfenidone DRUG

Treatment with pirfenidone 801 mg (3 pills of 267 mg each), three times daily.

Also known as: Deskar, Esbriet

Pirfenidone

Placebo DRUG

Placebo (3 pills), three times daily.

Also known as: Inactive matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For the portion of the protocol involving continuations of pirfenidone treatment, the criteria are simply previous enrollment in 97-HG-0085.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• William Gahl, M.D.: lead
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Anikster Y, Huizing M, White J, Shevchenko YO, Fitzpatrick DL, Touchman JW, Compton JG, Bale SJ, Swank RT, Gahl WA, Toro JR. Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico. Nat Genet. 2001 Aug;28(4):376-80. doi: 10.1038/ng576.

  PMID: 11455388 BACKGROUND

• Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998 Apr 30;338(18):1258-64. doi: 10.1056/NEJM199804303381803.

  PMID: 9562579 BACKGROUND

• Gahl WA, Brantly M, Troendle J, Avila NA, Padua A, Montalvo C, Cardona H, Calis KA, Gochuico B. Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome. Mol Genet Metab. 2002 Jul;76(3):234-42. doi: 10.1016/s1096-7192(02)00044-6.

  PMID: 12126938 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Albinism; Metabolism, Inborn Errors; Albinism, Oculocutaneous; Platelet Storage Pool Deficiency; Pulmonary Fibrosis; Hermanski-Pudlak Syndrome

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Hemorrhagic Disorders; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited

Limitations and Caveats

Study enrollment progressed more slowly than anticipated (spanning \>3 years instead of one). The Data Safety and Monitoring Board performed an interim analysis one year after 30 subjects enrolled and directed the study to stop due to futility.

Results Point of Contact

• Title: Dr. William A. Gahl
• Organization: National Human Genome Research Institute

gahlw@mail.nih.gov

301-402-2739

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Director, National Human Genome Research Institute

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: September 1, 2005
• Primary Completion: September 1, 2009
• Study Completion: May 9, 2016
• Last Updated: October 16, 2017
• Results First Posted: January 26, 2012

Record last verified: 2017-09

Locations

US (1)