Panhematin for Prevention of Acute Attacks of Porphyria
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02922413|
Recruitment Status : Recruiting
First Posted : October 4, 2016
Last Update Posted : February 8, 2023
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
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
|Condition or disease||Intervention/treatment||Phase|
|Acute Intermittent Porphyria Hereditary Coproporphyria Variegate Porphyria||Biological: Hemin for injection Other: Placebo||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Two group parallel blinded study comparing active drug and placebo|
|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.|
|Official Title:||Safety and Efficacy of Panhematin™ for Prevention of Acute Attacks of Porphyria|
|Actual Study Start Date :||October 30, 2015|
|Estimated Primary Completion Date :||January 6, 2024|
|Estimated Study Completion Date :||January 6, 2025|
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 Name: Hematin
Placebo Comparator: Placebo
A double blind dose of saline.
- Occurrence of an acute attack of porphyria after treatment [ Time Frame: 1-4 weeks ]To evaluate in 20 patients who are on a Panhematin™ prophylactic regimen whether blinded administration of Panhematin™ is more effective than placebo in preventing an attack within the next 1-4 weeks. The emphasis will be placed on prevention of attacks in the next week.
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1-4 weeks ]To evaluate in 20 patients whether hemin reconstituted with 25% human albumin is as safe and well tolerated as placebo when administered in a blinded fashion. Safety parameters will include the frequency and severity of phlebitis, nausea, vomiting and coagulation abnormalities.
- Effects on levels of porphobilinogen [ Time Frame: 1-4 weeks ]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.
- Effects of age [ Time Frame: 1-4 weeks ]To evaluate effects of age, as an example of clinical features, on response to preventive administration of Panhematin™.
- Effects of the nature of the porphobilinogen deaminase (PBGD) mutation [ Time Frame: 1-4 weeks ]To evaluate effects of the nature or the PBGD mutation on response to preventive Panhematin™
- Frequency of injection site complications [ Time Frame: 1-4 weeks ]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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Male or female aged 18 years
- Willing to provide written informed consent
- 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.
- Symptoms such as abdominal, back or limb pain are explained by another condition, as judged by the investigator
- Known or suspected allergy to Panhematin™ or related products
- A known or suspected allergy to human albumin
- 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
- Previous randomization in this trial
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02922413
|Contact: Karl E Anderson, MDemail@example.com|
|Contact: Csilla Hallberg, MD||409-772-4661||ckhallbe@UTMB.EDU|
|United States, Texas|
|University of Texas Medical Branch||Recruiting|
|Galveston, Texas, United States, 77555|
|Contact: Karl E Anderson, MD 409-772-4661 firstname.lastname@example.org|
|Contact: Csilla Hallberg, MD 409-772-4661 ext 24661 ckhallbe@UTMB.EDU|
|Principal Investigator:||Karl E Anderson, MD||University of Texas|
Documents provided by The University of Texas Medical Branch, Galveston:
|Responsible Party:||The University of Texas Medical Branch, Galveston|
|Other Study ID Numbers:||
FD-R-03720 ( Other Grant/Funding Number: FDA - OOPD )
|First Posted:||October 4, 2016 Key Record Dates|
|Last Update Posted:||February 8, 2023|
|Last Verified:||February 2023|
Porphyria, Acute Intermittent
Skin Diseases, Genetic
Genetic Diseases, Inborn
Digestive System Diseases