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Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)

Primary Purpose

Erythropoietic Protoporphyria

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Afamelanotide

Placebo

About this trial

This is an interventional prevention trial for Erythropoietic Protoporphyria focused on measuring Erythropoietic Protoporphyria, EPP, Afamelanotide

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female subjects 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 (inclusive)
Written informed consent prior to the performance of any study-specific procedures.

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 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 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).
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 of 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.

Sites / Locations

HUS:n Iho-ja allergiasairaala (Skin and Allergy Hospital)
Centre Français des Porphyries, Hôpital Louis Mourier
Department of Dermatology , Heinrich-Heine-University Duesseldorf
Beaumont Hospital, Department of Dermatology
Academisch Ziekenhuis Maastricht
Erasmus Medical Center
St Woolos Hospital
Photobiology Unit - Hope Hospital, University of Manchester

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Afamelanotide

Placebo

Arm Description

Outcomes

Primary Outcome Measures

The Duration of Direct Sunlight Exposure Between 10:00 and 15:00 Hours on Days When Patients Did Not Report Phototoxicity-related Pain (Likert Pain Scale Score of 0)

Secondary Outcome Measures

Number of Phototoxic Reactions

Quality of Life Measured by Patient Completed Questionnaire

Free Protoporphyrin IX Level

Treatment Emergent Adverse Events

Full Information

NCT ID

NCT00979745

First Posted

September 17, 2009

Last Updated

September 16, 2021

Sponsor

Clinuvel Pharmaceuticals Limited

1. Study Identification

Unique Protocol Identification Number

NCT00979745

Brief Title

Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)

Official 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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Clinuvel Pharmaceuticals Limited

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Afamelanotide is a man-made drug being studied for use as a preventative medication for EPP sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH) and is not yet available on the market. The purpose of this study is to look at whether afamelanotide can reduce the number and severity of EPP symptoms when patients are exposed to light. This study will also look at how the drug is tolerated when taken by people with EPP. The study will involve the use of an implant, which comes in the form of a small rod (approximately 2 cm x 0.15 cm) to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication). Over 450 subjects have been treated with afamelanotide to date with no serious safety concerns identified. For this study, afamelanotide has been formulated as a controlled release depot injection (implant). This means that the afamelanotide will be released slowly into the body over a few days. Once inserted, the implant will remain in the body after afamelanotide has been released and will slowly dissolve. This study will help to provide more information about afamelanotide. This information will be used to determine the safety and efficacy (the ability of the drug to produce an effect) of this drug in EPP sufferers. Up to 70 people will participate in this study from study sites across Europe.

Detailed Description

PURPOSE: To determine whether afamelanotide can reduce the severity of phototoxic reactions in patients with EPP. THEORETICAL FRAMEWORK: EPP is a genetic photosensitivity disorder where the mainstays of management are covering up from sunlight, systemic beta carotene and the use of controlled courses of UVR treatment. One of the mechanisms for the protective effects of UVR treatment is the increase in melanin content of the skin. UVR treatment causes DNA damage to skin cells and increases the risk for skin cancers, hence it is unwise for this to be used on a recurring basis. Afamelanotide, through its ability to stimulate melanin production without causing the DNA damage associated with UVR treatment, appears to be a promising agent to combat this distressing disorder. STUDY DESIGN: This is a phase III, randomised, placebo controlled study to evaluate the safety and efficacy of subcutaneous implants of afamelanotide in patients suffering from EPP. The study will be performed in compliance with Good Clinical Practice (GCP) including the archiving of essential documents. METHODOLOGY: The target population consists of male and female participants. Up to 70 patients with diagnosed EPP (from past case history) and fulfilling the necessary inclusion/exclusion criteria will be enrolled. Potential study patients will be identified from each centre's records of patients with well characterised history (or documented diagnosis) of EPP. Patients will be enrolled and will receive afamelanotide (16 mg implants) or placebo according to the following dosing regime: Group A will be administered active implants on Days 0, 60, 120, 180 and 240. Group B will be administered placebo implants on Days 0, 60, 120, 180 and 240.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Erythropoietic Protoporphyria

Keywords

Erythropoietic Protoporphyria, EPP, Afamelanotide

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

74 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Afamelanotide

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Afamelanotide

Other Intervention Name(s)

CUV1647

Intervention Description

One 16mg subcutaneous implant every 2 months for 9 months.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

One 16mg subcutaneous implant every 2 months for 9 months.

Primary Outcome Measure Information:

Title

The Duration of Direct Sunlight Exposure Between 10:00 and 15:00 Hours on Days When Patients Did Not Report Phototoxicity-related Pain (Likert Pain Scale Score of 0)

Time Frame

From baseline to Day 270

Secondary Outcome Measure Information:

Title

Number of Phototoxic Reactions

Time Frame

9 months

Title

Quality of Life Measured by Patient Completed Questionnaire

Time Frame

9 months

Title

Free Protoporphyrin IX Level

Time Frame

9 months

Title

Treatment Emergent Adverse Events

Time Frame

9 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female subjects 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 (inclusive) Written informed consent prior to the performance of any study-specific procedures. 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 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 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). 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 of 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.

Overall Study Officials: