Controlled Trial of Panhematin in Treatment of Acute Attacks of Porphyria

NCT02180412 | Completed Phase 2 Results DMC

• 2 other identifiers: 10-203FD-R-03720
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Acute Porphyrias

Keywords

Acute porphyria; Hemin

Outcome Measures

Primary Outcomes (1)

• Difference in NRS Pain Score Between Baseline and 12 Hours

  The difference in the pre-infusion NRS pain scores and NRS pain score 12 hours from the infusion start time. To define this variable, all blinded study treatment infusion times were compared with the pain score survey times. The pain score closest to but prior to the infusion time was the pre-infusion pain score. Numeric rating scale for pain (0-10; 0=no pain, 10=most severe pain).

  Baseline and 12 hours

Secondary Outcomes (1)

• Biochemical Effects of Panhematin In Participants Treated Early For Attacks of Porphyria

  Day 1 (baseline), Day 2, Day 3 and Day 4

Other Outcomes (3)

• Effects of Clinical Features on Response to Panhematin

  4 days

• Effects of Genetic Features on Response to Panhematin

  4 days

• Use of Reconstitution of Panhematin With Albumin

  4 days

Study Arms (2)

Panhematin

EXPERIMENTAL

Panhematin plus glucose

Biological: Panhematin; Other: Glucose

Placebo

PLACEBO COMPARATOR

Placebo (saline) plus glucose

Other: Glucose

Interventions

Panhematin BIOLOGICAL

Glucose loading

Also known as: Glucose

Panhematin

Glucose OTHER

Glucose is administered to both groups as routine care.

Panhematin; Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead

Study Sites (1)

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

MeSH Terms

Conditions

Porphyria, Acute Intermittent

Interventions

Hemin; Glucose

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Porphyrias; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Heme; Metalloporphyrins; Porphyrins; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pigments, Biological; Biological Factors; Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Dr. Karl Anderson, MD
• Organization: University of Texas Medical Branch, Galveston

kanderso@utmb.edu

409-772-9092

Study Officials

• Karl E Anderson, MD

  UT, Galveston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: July 2, 2014
• Study Start: April 28, 2014
• Primary Completion: February 3, 2022
• Study Completion: February 3, 2022
• Last Updated: April 11, 2025
• Results First Posted: April 3, 2025

Record last verified: 2025-04

Locations

US (1)