Hermansky-Pudlak syndrome (HPS) is a rare disorder of
oculocutaneous albinism, platelet dysfunction, and in some subtypes, fatal
pulmonary fibrosis. There is no effective treatment for the
pulmonary fibrosis except
lung transplantation, but an initial trial using
pirfenidone, an anti-fibrotic agent, showed promising results. The current, randomized, placebo-controlled, prospective, double-blind trial investigated the safety and efficacy of
pirfenidone for mild to moderate HPS-1 and 4
pulmonary fibrosis. Subjects were evaluated every 4 months at the National Institutes of Health Clinical Center, and the primary outcome parameter was change in forced vital capacity using repeated measures analysis with random coefficients. Thirty-five subjects with HPS-1
pulmonary fibrosis were enrolled during a 4-year interval; 23 subjects received
pirfenidone and 12 received placebo. Four subjects withdrew from the trial, 3 subjects died, and 10 serious adverse events were reported. Both groups experienced similar side effects, especially
gastroesophageal reflux. Interim analysis of the primary outcome parameter, performed 12 months after 30 patients were enrolled, showed no statistical difference between the placebo and
pirfenidone groups, and the study was stopped due to futility. There were no significant safety concerns. Other clinical trials are indicated to identify single or multiple
drug regimens that may be effective in treatment for progressive HPS-1
pulmonary fibrosis.