Phase III Confirmatory Study in Erythropoietic Protoporphyria
Condition: Erythropoietic Protoporphyria
MeSH terms: Protoporphyria, Erythropoietic
Intervention: Afamelanotide; Placebo
Intervention description: One 16mg subcutaneous implant every 2 months for 6 months.; One placebo subcutaneous implant every 2 months for 6 months
Intervention MeSH terms: Afamelanotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 93.0
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). Between 75 and 100 eligible patients will be enrolled.
      Patients 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

      The number and severity of phototoxic reactions, the type and duration of sun exposure,
      treatment-emergent adverse events and the use of concomitant medication will be recorded by
      patients in study diaries between Days 0 and 180. Quality of life will be measured using the
      DLQI and EPP-QoL at Days 0, 60, 120 and 180. Participants will visit the clinic on Days 60,
      120 and 180 for assessments of adverse events.

      A subset of patients will be photoprovoked on the lower back and dorsal surface of the hand
      and the minimal symptom dose (MSD) will be determined on Days 0, 30, 60, 90 and 120.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects with characteristic symptoms of EPP phototoxicity and a
             biochemically-confirmed diagnosis of EPP.

          -  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 polymorphic light eruption, actinic prurigo, discoid
             lupus erythematosus, chronic actinic dermatitis 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.

          -  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).