Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)

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.

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.