Purpose

The purpose of this study is to determine if Panhematin is safe and effective for prevention of acute attacks of porphyria. The study aims to provide high quality evidence for the use on hemin for prevention of acute attacks of porphyria. High quality studies have not been done previously for treating or preventing acute attacks with hemin. The lack of strong evidence for efficacy of hemin for treatment and prevention of attacks limits its availability for patients with acute porphyrias. Funding source: FDA Office of Orphan Product Development (FDA OOPD) FD-R-03720

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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. Subjects 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 they will have had 6 or more attacks in one year before starting hemin prophylaxis.

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Two group parallel blinded study comparing active drug and placebo
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Administered doses are shielded from view. The pharmacy and one nurse who administers the drug intravenously will not be blinded.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Hemin for injection
Double blind doses of Panhematin 4 mg/kg body weight reconstituted with 25% human albumin and infused over at least one hour.
  • Biological: Hemin for injection
    Panhematin 4 mg/kg body weight reconstituted with 25% human albumin infused intravenously over at least 1 hour.
    Other names:
    • Hematin
Placebo Comparator
Placebo
A double blind dose of saline.
  • Other: Placebo
    Saline infusion

Recruiting Locations

University of Texas Medical Branch
Galveston, Texas 77555
Contact:
Karl E Anderson, MD
409-772-4661
kanderso@utmb.edu

More Details

NCT ID
NCT02922413
Status
Recruiting
Sponsor
The University of Texas Medical Branch, Galveston

Study Contact

Karl E Anderson, MD
409-772-4661
kanderso@utmb.edu

Detailed Description

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 subjects with well-documented acute porphyria (acute intermittent porphyria, hereditary coproporphyria or variegate porphyria). Subjects 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 they 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. Double blind Panhematin™ or placebo will be given. The number of doses will correspond to the number of doses that a subject receives in approximately one week for their prophylactic regimen. An interim analysis will be carried out after completion of 10 subjects to assess progress and possibly adjust the sample size. The trial consists of the following visits:

- A screening visit to determine eligibility and obtain informed consent.

- A treatment visit for administration of double blind prophylactic doses of Panhematin™ or placebo corresponding to the number of doses the subject receives for their prophylactic regimen within approximately one week.

- 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 Subjects 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 one or more preventive doses of either Panhematin™ (4 mg/kg) or placebo, the number of which will correspond to the number of prophylactic doses they have been receiving within approximately one week for prophylaxis. A recurrent attack within the next 1, 2, 3 and 4 weeks will represent treatment failures. Because at study entry most subjects 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 a subject's usual treatment location.

It is intended that 20 subjects will complete treatment with blinded treatment and at least 4 weeks of follow up. A completed subject 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.