Multicentre Phase III Erythropoietic Protoporphyria Study
Condition: Erythropoietic Protoporphyria
MeSH terms: Protoporphyria, Erythropoietic
Intervention: Afamelanotide; Placebo
Intervention description: 16mg subcutaneous implant; Placebo subcutaneous implant
Intervention MeSH terms: Afamelanotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Erythropoietic Protoporphyria; EPP; Afamelanotide

Summary:

      This was a phase III, multicentre, randomised, double-blind, placebo-controlled study, to
      evaluate the safety and efficacy of subcutaneous bioresorbable afamelanotide implants in
      patients with Erythropoietic Protoporphyria (EPP).

      The study was conducted with two parallel study arms with crossover between treatments every
      60 days.

      Eligible patients were randomised to a treatment group, and received implants of active
      treatment (afamelanotide 16mg) or placebo, in an alternating crossover fashion according to
      the following dosing regime:

        -  Group A was administered active implants on Days 0, 120, 240 and placebo implants on
           Days 60, 180, 300

        -  Group B was administered placebo implants on Days 0, 120, 240 and active implants on
           Days 60, 180, 300
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients 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.

          -  Written informed consent prior to the performance of any study-specific procedure.

        Exclusion Criteria:

          -  Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine
             or other local anaesthetic 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.

          -  Diagnosed with HIV/AIDS or hepatitis.

          -  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).

          -  History of disorders of the gastrointestinal, hepatic, renal, cardiovascular,
             respiratory, endocrine (including diabetes, Cushing's syndrome, Addison's disease,
             Peutz-Jeagher syndrome), neurological (including seizures), haematological (especially
             anaemia of less than 10 g/100 mL) or systemic disease judged to be clinically
             significant by the Investigator.

          -  Major medical or psychiatric illness

          -  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 was 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).

          -  Participation in a clinical trial of an investigational agent within 30 days prior to
             the screening visit.

          -  Use of regular medications as specified in protocol Section 5.4 Prior and Concomitant
             Therapy.

          -  Any factors that may affect skin reflectance measurements.