Panhematin for Prevention of Acute Attacks of Porphyria

Safety and Efficacy of Panhematin™ for Prevention of Acute Attacks of Porphyria

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

Study Overview

• Status: Terminated
• Conditions: Hereditary Coproporphyria; Acute Intermittent Porphyria; Variegate Porphyria
• Intervention / Treatment: Other: Placebo; Biological: Hemin for injection

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Acute Attacks of Porphyria After Treatment	Participants were interviewed weekly by telephone to record the number of acute porphyria attacks after initial treatment with Panhematin or placebo.	1-4 weeks
Number of Participants With Treatment-Related Serious Adverse Events	The number of participants who experience treatment-related serious adverse events (SAEs) as assessed and graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	1-4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on levels of porphobilinogen	To evaluate the biochemical effects of Panhematin™ in patients treated with Panhematin™ to prevent attacks of acute porphyria by measuring urinary porphobilinogen and serum porphobilinogen. This will determine whether biochemical measurements are predictive of efficacy in preventing an attack.	1-4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on Levels of Porphobilinogen	To evaluate the biochemical effects of Panhematin™ in patients treated with Panhematin™ to prevent attacks of acute porphyria by measuring urinary porphobilinogen and serum porphobilinogen. This will determine whether biochemical measurements are predictive of efficacy in preventing an attack.	1-4 weeks
Effects of Age	To evaluate effects of age, as an example of clinical features, on response to preventive administration of Panhematin™.	1-4 weeks
Effects of the Nature of the Porphobilinogen Deaminase (PBGD) Mutation	To evaluate effects of the nature or the PBGD mutation on response to preventive Panhematin™	1-4 weeks
Frequency of Injection Site Complications	To evaluate the use of Panhematin™ reconstituted with 25% human albumin in patients treated to prevent acute attacks of porphyria in terms of the frequency of injection site complications, which may include thrombosis or inflammation.	1-4 weeks

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Investigators: Principal Investigator: Karl E Anderson, MD, University of Texas

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2015
• Primary Completion (Actual): December 27, 2023
• Study Completion (Actual): December 27, 2023

Study Registration Dates

• First Submitted: January 1, 2016
• First Submitted That Met QC Criteria: September 29, 2016
• First Posted (Estimated): October 4, 2016

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Porphyria; Heme
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Skin Diseases; Skin Diseases, Genetic; Porphyrias, Hepatic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Coproporphyria, Hereditary; Porphyrias; Porphyria, Acute Intermittent; Porphyria, Variegate; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Administration Routes; Drug Therapy; Azoles; Pigments, Biological; Biological Factors; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Pyrroles; Macrocyclic Compounds; Porphyrins; Tetrapyrroles; Heme; Metalloporphyrins; Injections; Hemin
• Other Study ID Numbers: 14-0188; FD-R-03720 (Other Grant/Funding Number: FDA - OOPD)