Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP) - Full Text View

Sponsor:	Clinuvel Pharmaceuticals Limited
Information provided by:	Clinuvel Pharmaceuticals Limited
ClinicalTrials.gov Identifier:	NCT00979745

Purpose

Afamelanotide is a man-made drug being studied for use as a preventative medication for EPP sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH) and is not yet available on the market.

The purpose of this study is to look at whether afamelanotide can reduce the number and severity of EPP symptoms when patients are exposed to light. This study will also look at how the drug is tolerated when taken by people with EPP.

The study will involve the use of an implant, which comes in the form of a small rod (approximately 2 cm x 0.15 cm) to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).

Over 450 subjects have been treated with afamelanotide to date with no serious safety concerns identified. For this study, afamelanotide has been formulated as a controlled release depot injection (implant). This means that the afamelanotide will be released slowly into the body over a few days. Once inserted, the implant will remain in the body after afamelanotide has been released and will slowly dissolve.

This study will help to provide more information about afamelanotide. This information will be used to determine the safety and efficacy (the ability of the drug to produce an effect) of this drug in EPP sufferers.

Up to 70 people will participate in this study from study sites across Europe.

Condition	Intervention	Phase
Erythropoietic Protoporphyria	Drug: Afamelanotide Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)

Resource links provided by NLM:

Genetics Home Reference related topics: porphyria

U.S. FDA Resources

Further study details as provided by Clinuvel Pharmaceuticals Limited:

Primary Outcome Measures:

Severity of phototoxic reaction measured by visual analogue scale [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of phototoxic reactions [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Quality of life measured by patient completed questionnaire [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Free protoporphyrin IX level [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Treatment emergent adverse events [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	70
Study Start Date:	September 2009
Study Completion Date:	May 2011
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Afamelanotide	Drug: Afamelanotide One 16mg subcutaneous implant every 2 months for 9 months. Other Name: CUV1647
Placebo Comparator: Placebo	Drug: Placebo One 16mg subcutaneous implant every 2 months for 9 months. Other Name: Placebo

Detailed Description:

PURPOSE:

To determine whether afamelanotide can reduce the severity of phototoxic reactions in patients with EPP.

THEORETICAL FRAMEWORK:

EPP is a genetic photosensitivity disorder where the mainstays of management are covering up from sunlight, systemic beta carotene and the use of controlled courses of UVR treatment. One of the mechanisms for the protective effects of UVR treatment is the increase in melanin content of the skin. UVR treatment causes DNA damage to skin cells and increases the risk for skin cancers, hence it is unwise for this to be used on a recurring basis. Afamelanotide, through its ability to stimulate melanin production without causing the DNA damage associated with UVR treatment, appears to be a promising agent to combat this distressing disorder.

STUDY DESIGN:

This is a phase III, randomised, placebo controlled study to evaluate the safety and efficacy of subcutaneous implants of afamelanotide in patients suffering from EPP. The study will be performed in compliance with Good Clinical Practice (GCP) including the archiving of essential documents.

METHODOLOGY:

The target population consists of male and female participants. Up to 70 patients with diagnosed EPP (from past case history) and fulfilling the necessary inclusion/exclusion criteria will be enrolled. Potential study patients will be identified from each centre's records of patients with well characterised history (or documented diagnosis) of EPP.

Patients will be enrolled and will receive afamelanotide (16 mg implants) or placebo according to the following dosing regime:

Group A will be administered active implants on Days 0, 60, 120, 180 and 240.
Group B will be administered placebo implants on Days 0, 60, 120, 180 and 240.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female subjects with a diagnosis of EPP (confirmed by elevated free protoporphyrin in peripheral erythrocytes) of sufficient severity that they have requested treatment to alleviate their symptoms.
Aged 18 - 70 years (inclusive)
Written informed consent prior to the performance of any study-specific procedures.

Exclusion Criteria:

Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic to be used during the administration of study medication.
EPP patients with significant hepatic involvement.
Personal history of melanoma or dysplastic nevus syndrome.
Current Bowen's disease, basal cell carcinoma, squamous cell carcinoma, or other malignant or premalignant skin lesions.
Any other photodermatosis such as PLE, DLE or solar urticaria.
Any evidence of clinically significant organ dysfunction or any clinically significant deviation from normal in the clinical or laboratory determinations.
Acute history of drug or alcohol abuse (in the last 12 months).
Patient assessed as not suitable for the study in the opinion of the Investigator (e.g. noncompliance history, allergic to local anaesthetics, faints when given injections or giving blood).
Female who is pregnant (confirmed by positive serum β-HCG pregnancy test prior to baseline) or lactating.
Females of child-bearing potential (pre-menopausal, not surgically sterile) not using adequate contraceptive measures (i.e. oral contraceptives, diaphragm plus spermicide, intrauterine device).
Sexually active men with partners of child bearing potential not using barrier contraception during the trial and for a period of three months thereafter.
Participation in a clinical trial of an investigational agent within 30 days prior to the screening visit.
Prior and concomitant therapy with medications which may interfere with the objectives of the study, including drugs that cause photosensitivity or skin pigmentation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00979745

Locations

Finland
HUS:n Iho-ja allergiasairaala (Skin and Allergy Hospital)
Helsinki, Finland
France
Centre Français des Porphyries, Hôpital Louis Mourier
Colombes, Cedex, France, 92701
Germany
Department of Dermatology , Heinrich-Heine-University Duesseldorf
Duesseldorf, Germany, 40225
Ireland
Beaumont Hospital, Department of Dermatology
Dublin, Ireland, 9
Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
United Kingdom
St Woolos Hospital
Newport, Wales, United Kingdom
Photobiology Unit - Hope Hospital, University of Manchester
Manchester, United Kingdom, M6 8HD

Sponsors and Collaborators

Clinuvel Pharmaceuticals Limited

Investigators

Principal Investigator:	Alex Anstey, MBBS, FRCP	St Woolos Hospital, Newport
Principal Investigator:	Jorge Frank, MD, PhD	Academisch Ziekenhuis Maastricht
Principal Investigator:	Raili Kauppinen, MD, PhD	University Central Hospital of Helsinki
Principal Investigator:	Eric JG Sijbrands, MD, PhD	Erasmus Medical Center, Rotterdam
Principal Investigator:	Jean-Charles Deybach, MD. PhD	Centre Francais des Porphyries, Hopital Louis Mourier, Colombes, France
Principal Investigator:	Sandra Hanneken, MD	Heinrich-Heine Universität, Düsseldorf, Germany
Principal Investigator:	Gillian M Murphy, MD PhD	Beaumont Hospital, Dublin, Ireland
Principal Investigator:	Lesley E Rhodes, MD PhD	Hope Hospital, University of Manchester, UK

More Information

No publications provided

Responsible Party:	Dr Dennis Wright, Clinuvel Pharmaceuticals Limited
ClinicalTrials.gov Identifier:	NCT00979745 History of Changes
Other Study ID Numbers:	CUV029
Study First Received:	September 17, 2009
Last Updated:	August 3, 2011
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO); Netherlands: Medical Ethics Review Committee (METC); United Kingdom: Medicines and Healthcare Products Regulatory Agency; United Kingdom: Research Ethics Committee; Finland: Finnish Medicines Agency; Finland: Ethics Committee; Germany: Ethics Commission; Germany: Federal Institute for Drugs and Medical Devices; Ireland: Research Ethics Committee; Ireland: Irish Medicines Board; France: Institutional Ethical Committee; France: Afssaps - French Health Products Safety Agency

Keywords provided by Clinuvel Pharmaceuticals Limited:

Erythropoietic Protoporphyria
EPP
Afamelanotide

Additional relevant MeSH terms:

Protoporphyria, Erythropoietic
Porphyrias, Hepatic
Liver Diseases
Digestive System Diseases
Porphyrias
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Skin Diseases, Genetic

Skin Diseases
Skin Diseases, Metabolic
Metabolic Diseases
Alpha-MSH
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012