Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)
Condition: Erythropoietic Protoporphyria
MeSH terms: Protoporphyria, Erythropoietic
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

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.
    

Intervention name(s): Afamelanotide; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): One 16mg subcutaneous implant every 2 months for 9 months.; One 16mg subcutaneous implant every 2 months for 9 months.
Other intervention name(s): CUV1647
Intervention MeSH terms: Afamelanotide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Erythropoietic Protoporphyria; EPP; Afamelanotide