Phase II 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 6 months. (3 implants in total); One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
Intervention MeSH terms: Afamelanotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Erythropoietic Protoporphyria; EPP; Afamelanotide

Summary:

      This is a randomized placebo-controlled study to be conducted in two parallel study arms for
      a six month period (three doses). Approximately 10 eligible patients per center will be
      enrolled and will receive afamelanotide (16 mg implants) or placebo according to the
      following dosing regimen:

        -  Group A will be administered afamelanotide implants on Days 0, 60 and 120

        -  Group B will be administered placebo implants on Days 0, 60 and 120

      To determine eligibility for study inclusion, patients will undergo a screening evaluation 7
      to 14 days prior to the administration of the first dose. The number and severity of
      phototoxic reactions will be determined Days 60, 120, and 180. Quality of life will be
      measured using the EPP specific questionnaire (EPP-QoL) every 60 days and the DLQI
      questionnaire every 7 days, beginning at Day 0 until Day 180. Participants will visit the
      clinic on Days 60, 120 and 180 for assessments of adverse events.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects with characteristic photosensitivity of EPP symptoms and
             positive diagnosis of EPP confirmed by laboratory result of elevated total
             protoporphyrin IX.

          -  Aged 18 years old and above (inclusive).

          -  Able to understand and sign the written Informed Consent Form.

          -  Willing to take precautions to prevent pregnancy until completion of the study (Day
             180).

        Exclusion Criteria:

          -  Any allergy to afamelanotide or the polymer contained in the implant or to lidocaine
             or other local anesthetic to be used during the administration of the 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 6 months).

          -  Patient assessed as not suitable for the study in the opinion of the Investigator
             (e.g. noncompliance history, allergic to local anesthetics, faints when given
             injections or giving blood).

          -  Participation in a clinical trial for 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 within
             60 days prior to the screening visit.

          -  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).