This is a Phase 2, randomized, blinded controlled study to compare treatment with Hemin 4 mg/kg daily plus glucose for 4 days to treatment with glucose alone in 30-40 patients with acute attacks of porphyria. The study will be conducted at multiple sites in the Porphyrias Consortium and aims to improve the evidence base for this treatment for acute porphyric attacks. The consortium investigators have experience in conducting controlled studies in porphyrias, including studies in patients with acute attacks. The National Institutes of Health (NIH) Rare Disease Clinical Research Network supports development of study materials, web-based data entry, data warehousing, and monitoring at multiple study sites, and has established a data and safety monitoring board. The manufacturer has committed drug for the study. The American Porphyria Foundation, a longstanding and effective patient support group that is also part of the Consortium, will assist with patient recruitment. Infrastructure at all sites will include facilitis of NIH-funded Clinical and Translational Science Awards.
The specific aims of this proposal are: 1) To provide evidence for efficacy of human hemin for treatment of acute attacks of porphyria by conducting a double-blind placebo-controlled Phase 2 clinical trial in 30-40 patients with well documented acute porphyria;2) To obtain samples for a study that aims for a better understanding of the mechanism of the beneficial effects of hemin administered in porphyria by studying regulation of genes for heme pathway enzymes and heat shock and stress response genes in peripheral blood mononuclear cells (PBMCs) obtained from acute porphyria patients before and after treatment with hemin. This will be in collaboration with Dr.Herbert Bonkovsky at Carolinus Medical Center in Charlotte, NC;3) To provide evidence for efficacy and safety of hemin for prevention of recurring attacks of porphyria by conducting a double-blind placebo-controlled Phase 2 clinical trial in 20 patients with well documented acute porphyria;4) To explore the feasibility and utility of a blinded placebo-controlled crossover approach to assessing the efficacy of hemin in individual patients with acute porphyria. Secondary and exploratory objectives will include a comparison of the biochemical effects of Panhematin and glucose, to evaluate effects of clinical features, such as sex, age and the factors that precipitat attacks of porphyria on response to Panhematin and glucose, to evaluate effects of genetic features, including the nature or the underlying mutation on treatment response to Panhematin, and to evaluate the use of Panhematin reconstituted with 25% human albumin in patients with acute attacks of porphyria.
Hemin for injection (Panhematin, Lundbeck) was the first drug approved under the Orphan Drug Act, but its efficacy has remained in question because controlled studies are lacking. A randomized, blinded controlled study will compare treatment with Panhematin 4mg/kg daily plus glucose for 4 days to treatment with glucose alone in 30-40 patients with acute attacks of porphyria, and will be conducted within the Porphyrias Consortium. This revised project now proposes an additional analogous controlled study on the use of Panhematin to prevent attacks and studies of efficacy in individual patients, and will provide high quality evidence for efficacy and safety of the drug viewed as the most important available treatment for acute attacks of porphyria.