Panhematin for Prevention of Acute Attacks of Porphyria

This is a double-blind, randomized, placebo-controlled, parallel group trial investigating
the efficacy and safety of Panhematin™ for preventing acute attacks in at least 20 patients
with well-documented acute porphyria (acute intermittent porphyria, hereditary coproporphyria
or variegate porphyria). These patients will (1.) have had frequent attacks in the past, with
symptoms such as abdominal, back and/or limb pain and diagnosed after exclusion of other
causes, and (2.) be on hemin prophylaxis for prevention of frequent attacks. It is expected
that patients will have had 6 or more attacks in one year before starting hemin prophylaxis.
This would be considered justification for a preventive regimen of hemin on clinical grounds.
A single double blind dose of Panhematin™ or placebo will be given. An interim analysis will
be carried out after completion of 10 patients to assess progress and possibly adjust the
sample size. The trial consists of the following:

- A screening visit to determine eligibility and obtain informed consent

- A treatment visit for administration of a double blind prophylactic dose of Panhematin™
or placebo

- Follow up visit at 1, 2, 3, and 4 weeks to assess response to the infusion of
Panhematin™ or placebo. These visits will be in person or by telephone.

- Additional visits may be scheduled if needed, for example for treatment of symptoms.

- Follow-up visits 3 and 6 months after the end of treatment either in person or by
telephone Patients will have laboratory documentation of one of the acute porphyrias.
Molecular documentation is also expected, although rarely a causative mutation cannot be
detected. Upon entry into the study they will be given in a blinded fashion a single
preventive dose of either Panhematin™ (4 mg/kg) or placebo. A recurrent attack within
the next 1, 2, 3 and 4 weeks will represent treatment failures. Because at study entry
most patients are expected to be on weekly prophylactic hemin treatment, and hemin is a
short-acting drug, emphasis in the analysis will be on attacks occurring within 1 week
after study treatment.

Any attacks that occur during the study will be treated according to standard of care, which
may include Panhematin™, either at the study site or at the patient's usual treatment
location.

It is intended that 20 patients will complete treatment with a single blinded dose and at
least 4 weeks of follow up. A completed patient is one who meets all entrance criteria, has
no exclusion criteria and completes the single dosing and at least one week of follow up, or
is withdrawn because of an adverse event.

Inclusion Criteria:

1. Male or female aged 18 years

2. Willing to provide written informed consent

3. A diagnosis of acute intermittent porphyria, hereditary coproporphyria or variegate
porphyria confirmed by the following criteria, which are based on the criteria for
enrollment in the Longitudinal Study of the Porphyrias Consortium. For each type of
porphyria, the inclusion criteria are based on 1) clinical features, 2) biochemical
findings, as documented by laboratory reports (or copies) of porphyria-specific
testing, and 3) molecular studies to identify a mutation in a porphyria-related gene.
Equivocal biochemical measurements may require confirmatory testing. Testing for a
disease-causing mutation must be attempted, but an identified mutation is not
essential for enrollment, since it is known that a mutation cannot be found in a small
fraction (<5%) of biochemically proven cases of porphyria.

Exclusion Criteria:

1. Symptoms such as abdominal, back or limb pain are explained by another condition, as
judged by the investigator

2. Known or suspected allergy to Panhematin™ or related products

3. A known or suspected allergy to human albumin

4. Any disease or condition that the investigator judges would lead to an unacceptable
risk to the patient or interfere with the successful collection of data for the trial

5. Previous randomization in this trial