Clinical Trial: Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Therapeutic Clinical Trial of Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome

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. 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.


Detailed Summary:

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease consisting of oculocutaneous albinism and a platelet storage pool defect. The most serious complication of this disorder, which is common in Puerto Rico, is pulmonary fibrosis, generally fatal in the fourth or fifth decade. There is no treatment for the pulmonary disease of HPS, which resembles idiopathic pulmonary fibrosis. However, a drug called pirfenidone has antifibrotic effects in animal models of lung fibrosis. Pirfenidone is an IND drug initially provided by Marnac, Inc.; InterMune, Inc., now holds the license. Pirfenidone inhibits cytokine-induced inflammation. Reported side effects include gastrointestinal upset, a photosensitivity rash, and palpitations. Between 1997 and 2001, we performed a randomized, placebo-controlled trial under this protocol that found pirfenidone to be safe and efficacious when analyzed using a repeated measures model. Using a random coefficients model, however, the data were definitive only in the restricted group of subjects whose initial forced vital capacity was greater than 50% of predicted. Because the repeated measures analysis had been chosen a priori as the optimal model, the DSMB stopped the study and directed that all patients receive pirfenidone. (Of the 23 original patients, 3 are still receiving pirfenidone under this protocol.)

Now, to prove efficacy of pirfenidone, we are conducting a block-randomized, placebo-controlled, double-blind trial involving up to 40 HPS patients whose forced vital capacity is 51-85% of predicted. For every patient randomly assigned to the placebo group, two will receive pirfenidone. Patients are largely drawn from the Puerto Rican population and are simultaneously enrolled in clinical protocol 95-HG-193. They are admitted to the NIH Clinical Center for 2-3 day admissions every 4 months. The primary efficacy variable is change
Sponsor: William Gahl, M.D.

Current Primary Outcome: Change in Forced Vital Capacity (36 Months) [ Time Frame: Measured at baseline and 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).


Original Primary Outcome:

Current Secondary Outcome:

  • Change in Forced Vital Capacity (12 Months) [ Time Frame: Measured at baseline and 12 months ]
    Change from baseline in the Forced Vital Capacity (FVC) measurement at 12 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).
  • Change in Total Lung Capacity (36 Months) [ Time Frame: Measured at baseline and 36 months ]
    Change from baseline in Total Lung Capacity (TLC) measured at 36 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.
  • Change in Total Lung Capacity (12 Months) [ Time Frame: Measured at baseline and 12 months ]
    Change from baseline in Total Lung Capacity (TLC) measured at 12 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.
  • Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (36 Months) [ Time Frame: Measured at baseline and 36 months ]
    Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 36 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.
  • Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (12 Months) [ Time Frame: Measured at baseline and 12 months ]
    Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 12 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.
  • Change in 6 Minute Walk Test (36 Months) [ Time Frame: Measured at baseline and 36 months ]
    Change from baseline of the 6 minute walk test (6MWT) at 36 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.
  • Change in 6 Minute Walk Test (12 Months) [ Time Frame: Measured at baseline and 12 months ]
    Change from baseline of the 6 minute walk test (6MWT) at 12 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.


Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: November 3, 1999
Date Started: September 2005
Date Completion: September 2020
Last Updated: October 5, 2015
Last Verified: October 2015