A MULTI-CENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Acute intermittent porphyria (AIP) is a genetic (autosomal dominant) disease due to a deficiency of porphobilinogen deaminase (PBGD). Excess porphobilinogen and other heme biosynthetic pathway intermediates accumulate in liver and plasma and are excreted in urine. Symptoms occur mostly as acute attacks due to effects on the nervous system. Standard therapies include intravenous glucose and hemin (hematin, heme albumin or heme arginate), but these are not always effective. The primary objective of this multi-center, double-blind, randomized, placebo-controlled, parallel group, Phase II-III trial is to investigate the biochemical efficacy of Porphozym(recombinant human porphobilinogen deaminase) on plasma porphobilinogen (PBG) in subjects with acute intermittent porphyria (AIP) during an attack. Secondary objectives include assessments of clinical efficacy and pharmacokinetics of rhPBGD in plasma. At least 36 subjects will be enrolled in the trial, both in Europe and the U.S., including up to 12 at UTMB. Potential patients who are likely to have recurrent attacks are informed of the study in advance and encouraged to come to the hospital early in an attack. After a screening period that is as short as possible (4 hours) subjects enrolled in the trial will be randomized to treatment with either Porphozym+ or placebo, as well as glucose. If the symptoms of porphyria become worse during treatment the trial drug may be discontinued and the patient treated with hemin. Treatment with trial drug is given over 48 hours, after which standard treatment, including hemin, may be given if clinically indicated.