Controlled Trial of Panhematin in Treatment of Acute Attacks of Porphyria

A Double-blind, Randomized, Placebo-controlled, Parallel Group Trial on the Efficacy and Safety of PanhematinTM in the Treatment of Acute Attacks of Porphyria

This study aims to provide high quality evidence for the effectiveness and safety of hemin (PanhematinTM , Recordati) for treatment of acute attacks of porphyria. These types of studies have not been done before with either PanhematinTM or the hemin preparation available in Europe (NormosangTM, Orphan Europe).

There are two treatment groups in this study. One group will be treated with PanhematinTM plus glucose, and the other group will be treated with glucose plus an inactive salt solution (called a "placebo"). To avoid prejudice, the treatment given to each participant will be blinded (meaning the participants and most of the hospital staff will not know which treatment the participant will receive) and randomized (meaning participants will have an equal chance of receiving either treatment, like the flip of a coin). A placebo-controlled, randomized study is the standard method used to prove treatments are effective and safe. PanhematinTM and glucose will be given in the same manner as is usual for treating an attack of porphyria. For participants who are chosen to receive the placebo, their treatment will be switched to real PanhematinTM at any time if their symptoms do not improve. This is called "rescue" treatment, and assures that they study is safe and patients who need hemin will receive it. Treatment with hemin will be for 4 days, or longer if needed. Since the study treatment is started as soon as possible after symptoms appear, there will be very little delay in providing hemin to those who need it. Funding Source - Office of Orphan Products Development (FDA OOPD)

Study Overview

• Status: Completed
• Conditions: Acute Porphyrias
• Intervention / Treatment: Biological: Panhematin; Other: Glucose

• Study Type: Interventional
• Enrollment (Actual): 25
• 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 to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female aged 18 years
• Willing to provide written informed consent
• Acute symptoms (7 days duration or less to time of enrollment) such as abdominal, back and/or limb pain, diagnosed by the investigator as caused by porphyria after initial evaluation has excluded other causes.
• Diagnosis of acute porphyria documented by a substantial increase in urinary or serum porphobilinogen (PBG).
• Type of acute porphyria confirmed by additional testing (in addition to increased PBG), which may be completed before or after treatment begins using pretreatment samples:
• For acute intermittent porphyria (AIP): Normal or only slight increases in plasma and fecal porphyrins. Most (~90 percent) will have deficient activity of erythrocyte porphobilinogen deaminase (PBGD), and almost all (>95 percent) will have a demonstrable disease-causing PBGD mutation.
• For hereditary coproporphyria (HCP): Substantial increases in fecal porphyrins (almost entirely coproporphyrin III). In the absence of skin photosensitivity, most will have normal or only slight increases in plasma porphyrins. Almost all (>95 percent) will have a demonstrable disease-causing coproporphyrinogen oxidase (CPO) mutation.
• For variegate porphyria (VP): Substantial increases in fecal porphyrins (mostly coproporphyrin III and protoporphyrin), increased plasma total porphyrins and a fluorescence emission maximum of diluted plasma at neutral pH near 626 nm. Almost all (~95 percent) will have a demonstrable disease-causing protoporphyrinogen oxidase (PPO) mutation.

Exclusion Criteria:

• Symptoms such as abdominal, back or limb pain are explained by another condition, as judged by the investigator
• Therapy with hemin within 7 days prior to enrollment in this study
• Known or suspected allergy to Panhematin™ or related products
• Preexisting coagulation defect or concurrent treatment with an anticoagulant
• Previously documented renal impairment defined as a serum creatinine above 1.7 mg/dL or 150 mmol/L.
• A diagnosis of diabetes mellitus, which might increase the risk of glucose infusion.
• Heart failure, significant chronic anemia or any disease or condition that the investigator judges would lead to an unacceptable risk to the patient or interfere with the successful collection of date for the trial
• Previous randomization in this trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panhematin; Panhematin plus glucose	Biological: Panhematin; Glucose loading; Other Names: Glucose; Other: Glucose; Glucose is administered to both groups as routine care.
Placebo Comparator: Placebo; Placebo (saline) plus glucose	Other: Glucose; Glucose is administered to both groups as routine care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scale	Numeric rating scale for pain (0-10; 0=no pain, 10=most severe pain)	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical effects of Panhematin	Porphyrin precursors and porphyrins	4 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of clinical features on response to Panhematin	Age, sex, exacerbating factors	4 days
Effects of genetic features on response to Panhematin	Types of mutations	4 days
Use of reconstitution of Panhematin with albumin	Frequency of side effects or adverse events	4 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2014
• Primary Completion (Actual): February 3, 2022
• Study Completion (Actual): February 3, 2022

Study Registration Dates

• First Submitted: June 25, 2014
• First Submitted That Met QC Criteria: June 30, 2014
• First Posted (Estimate): July 2, 2014

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Acute porphyria; Hemin
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Skin Diseases; Liver Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Porphyrias, Hepatic; Porphyria, Erythropoietic; Porphyrias; Porphyria, Acute Intermittent
• Other Study ID Numbers: 10-203; FD-R-03720 (Other Grant/Funding Number: FDA - OOPD)