Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)
Condition: Erythropoietic Protoporphyria
MeSH terms: Protoporphyria, Erythropoietic
Intervention: Afamelanotide; Placebo
Intervention description: One 16mg subcutaneous implant every 2 months for 9 months.; One 16mg subcutaneous implant every 2 months for 9 months.
Intervention MeSH terms: Afamelanotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Erythropoietic Protoporphyria; EPP; Afamelanotide

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.
    

Eligibility 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.