Panhematin for Prevention of Acute Attacks of Porphyria

Brief Title

Panhematin for Prevention of Acute Attacks of Porphyria

Official Title

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

Brief Summary

      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
    

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Occurrence of an acute attack of porphyria after treatment

Secondary Outcome

 Effects on levels of porphobilinogen

Condition

Acute Intermittent Porphyria

Intervention

Hemin for injection

Study Arms / Comparison Groups

 Hemin for injection
Description:  Double blind doses of Panhematin 4 mg/kg body weight reconstituted with 25% human albumin and infused over at least one hour.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

20

Start Date

October 30, 2015

Completion Date

September 2023

Primary Completion Date

September 2022

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Karl E Anderson, MD, 409-772-4661, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02922413

Organization ID

14-0188

Secondary IDs

FD-R-03720

Responsible Party

Sponsor

Study Sponsor

The University of Texas Medical Branch, Galveston


Study Sponsor

Karl E Anderson, MD, Principal Investigator, University of Texas


Verification Date

November 2020