Clinical trial NCT04053270: Multicentre Phase III Erythropoietic Protoporphyria Study
Official title: A Phase III, Multicentre, Randomised, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutanenous Bioresorbable CUV1647 Implants in Patients With Erythropoietic Protoporphyria (EPP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Erythropoietic Protoporphyria
Keywords: Erythropoietic Protoporphyria
EPP
Afamelanotide
Lead sponsor: Clinuvel Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2019-08-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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

Detailed description: Afamelanotide is a man-made drug being studied for use as a preventative medication for Erythropoietic Protoporphyria (EPP) sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH).

The study will involve the use of an implant, which comes in the form of a small rod to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).

This study aims to provide insight into the effectiveness of afamelanotide under normal conditions of use in EPP patients.

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.

Primary outcomes:
measure: Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population)
timeFrame: 0-360 days or Early Termination
measure: The Mean Number of Phototoxic Reactions (Study Efficacy Population)
timeFrame: 0-360 days or Early Termination
Secondary outcomes:
measure: Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population)
timeFrame: 0-360 days or Early Termination
measure: Skin Melanin Density (Study Completers Population)
timeFrame: Day0, Day14, Day30, Day60, Day74, Day90, Day120, Day150, Day180, Day210, Day240, Day270, Day300, Day330, Day360 or Early Termination
measure: Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population
timeFrame: Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination
measure: Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population
timeFrame: Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination
Other outcomes:
Locations:
Study officials:
affiliation: CLINUVEL PHARMACEUTICALS LTD
name: Head of Clinical Development
role: STUDY_DIRECTOR
References:
citation: Dwyer T, Muller HK, Blizzard L, Ashbolt R, Phillips G. The use of spectrophotometry to estimate melanin density in Caucasians. Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):203-6.