A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients with Erythropoietic Protoporphyria (EPP). - Multicentre Phase III EPP Study 2

• Register: EUCTR
• Last refreshed on: 3 April 2012
• Main ID: EUCTR2009-011018-51-IE
• Date of registration: 20/01/2010
• Prospective Registration: Yes
• Primary sponsor: Clinuvel Pharmaceuticals Limited
• Public title: A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients with Erythropoietic Protoporphyria (EPP). - Multicentre Phase III EPP Study 2
• Scientific title: A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients with Erythropoietic Protoporphyria (EPP). - Multicentre Phase III EPP Study 2
• Date of first enrolment: 09/03/2010
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011018-51
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, Ireland, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible to enter the study, patients must meet the following inclusion criteria:
- Male or female subjects with a positive diagnosis of EPP (confirmed by elevated free protoporphyrin in peripheral erythrocytes);
- Aged 18-70 years (inclusive); and
- Provide written Informed Patient Consent prior to the performance of any study-specific procedure.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
To be eligible to enter the study, patients must not meet any of the following exclusion criteria:
- Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic 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 12 months);
- 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 is pregnant (confirmed by positive serum ß-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);
- Sexually active men with partners of child bearing potential not using barrier contraception during the trial and for a period of three months thereafter;
- Participation in a clinical trial for an investigational agent within 30 days prior to the screening visit; and
- Prior and concomitant therapy with medications which may interfere with the objectives of the study, including drugs that cause photosensitivity or skin pigmentation.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Erythropoietic Protoporphyria (EPP).
MedDRA version: 12.1 Level: LLT Classification code 10015289 Term: Erythropoietic protoporphyria

Intervention(s)

Product Name: afamelanotide
Product Code: CUV1647
Pharmaceutical Form: Implant
INN or Proposed INN: Afamelanotide
CAS Number: 75921-69-6
Current Sponsor code: CUV1647
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 16-
Pharmaceutical form of the placebo: Implant
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: Secondary objectives:
- To determine whether afamelanotide can reduce the number of phototoxic reactions in patients with EPP;
- To evaluate the safety and tolerability of afamelanotide by measuring treatment-emergent adverse events (AEs);
- To determine whether afamelanotide can improve the quality of life of EPP patients;
- To determine the effect of afamelanotide on free protoporphyrin IX levels;
- To determine whether afamelanotide can increase the duration of sunlight tolerated by patients with EPP; and
- In a subset of patients, determine whether afamelanotide implants can reduce the susceptibility to provocation with a standardized light source (minimal symptom dose (MSD) and minimal erythema dose (MED))

Primary end point(s): Efficacy Endpoints:
Efficacy will be assessed by:
- Number and severity of phototoxic reactions;
- Quality of life measured with DLQI questionnaire and supplementary EPP specific questions;
- Free protoporphyrin IX in peripheral erythrocytes;
- Duration of sunlight exposure, as recorded in a patient diary; and
- In a subset of patients only.
o Minimal symptom dose (MSD) following photoprovocation on the lower back and dorsal surface of the hands; and
o Minimal erythema dose (MED) from phototesting on the lower back or buttocks

Safety and Tolerability Endpoints:
- Treatment-emergent adverse events (coded as MedDRA Preferred Terms);
- Changes in hematology, serum chemistry and urinalysis measurements from Screening to Study Days 60, 120, 180, 240, 270 and at Premature Termination Visit if applicable.

Main Objective: Primary objective:
- To determine whether afamelanotide can reduce the severity of phototoxic reactions in patients with EPP.

Secondary ID(s)

CUV029

2009-011018-51-NL