Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)

NCT ID: NCT00979745

Last Updated: 2021-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2011-05-31

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.

Conditions

Erythropoietic Protoporphyria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Afamelanotide

Group Type: EXPERIMENTAL

Afamelanotide

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Afamelanotide

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

CUV1647

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinuvel Pharmaceuticals Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Anstey, MBBS, FRCP

Role: PRINCIPAL_INVESTIGATOR

St Woolos Hospital, Newport

Jorge Frank, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Academisch Ziekenhuis Maastricht

Raili Kauppinen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Central Hospital of Helsinki

Eric JG Sijbrands, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Jean-Charles Deybach, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Francais des Porphyries, Hopital Louis Mourier, Colombes, France

Sandra Hanneken, MD

Role: PRINCIPAL_INVESTIGATOR

Heinrich-Heine Universität, Düsseldorf, Germany

Gillian M Murphy, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Beaumont Hospital, Dublin, Ireland

Lesley E Rhodes, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Hope Hospital, University of Manchester, UK

Locations

HUS:n Iho-ja allergiasairaala (Skin and Allergy Hospital)

Helsinki, , Finland

Centre Français des Porphyries, Hôpital Louis Mourier

Colombes, Cedex, France

Department of Dermatology , Heinrich-Heine-University Duesseldorf

Düsseldorf, , Germany

Beaumont Hospital, Department of Dermatology

Dublin, , Ireland

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

St Woolos Hospital

Newport, Wales, United Kingdom

Photobiology Unit - Hope Hospital, University of Manchester

Manchester, , United Kingdom

Countries

Finland; France; Germany; Ireland; Netherlands; United Kingdom

References

Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FPJ, Sijbrands EJG, de Rooij FWM, Lebwohl M, Naik H, Goding CR, Wilson JHP, Desnick RJ. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015 Jul 2;373(1):48-59. doi: 10.1056/NEJMoa1411481.

Reference Type: DERIVED

PMID: 26132941 (View on PubMed)

Other Identifiers

CUV029

Identifier Type: -

Identifier Source: org_study_id