Phase 3
N=100
Multicentre Phase III Erythropoietic Protoporphyria Study
Erythropoietic Protoporphyria
Bottom Line
View on ClinicalTrials.gov: NCT04053270 ↗Enrolled (actual)
100
Serious AEs
3.0%
Results posted
Oct 2019
Primary outcome: Primary: Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) — 39; 45; 129; 179 Days
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Afamelanotide (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Clinuvel Pharmaceuticals Limited
- Primary completion
- Dec 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) |
39; 45; 129; 179; 1126; 1237 | — |
| PRIMARY The Mean Number of Phototoxic Reactions (Study Efficacy Population) |
1.44; 2.64; 0.56; 0.11; 1.09; 0.79 | — |
| SECONDARY Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) |
339; 250; 969; 854; 2810; 2695 | — |
| SECONDARY Skin Melanin Density (Study Completers Population) |
3.42; 3.22; 3.75; 3.39; 3.86; 3.40 | — |
| SECONDARY Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population |
51.90; 54.22; 54.20; 54.85; 54.26; 54.68 | — |
| SECONDARY Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population |
51.41; 53.03; 52.31; 52.26; 53.16; 52.71 | — |
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.
Data sourced from ClinicalTrials.gov (NCT04053270). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.