Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)

NCT00979745 | Completed Phase 3 Results

• 1 other identifier: CUV029
• Study Type: interventional
• Target: 74
• Locations: 6 countries
• Sites: 8

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.

Conditions

Erythropoietic Protoporphyria

Keywords

Erythropoietic Protoporphyria; EPP; Afamelanotide

Outcome Measures

Primary Outcomes (1)

• 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)

  From baseline to Day 270

Secondary Outcomes (4)

• Number of Phototoxic Reactions

  9 months

• Quality of Life Measured by Patient Completed Questionnaire

  9 months

• Free Protoporphyrin IX Level

  9 months

• Treatment Emergent Adverse Events

  9 months

Study Arms (2)

Afamelanotide

EXPERIMENTAL

Drug: Afamelanotide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Afamelanotide DRUG

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

Also known as: CUV1647

Afamelanotide

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Clinuvel Pharmaceuticals Limited: lead

Study Sites (8)

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

Helsinki, Finland

Location

Centre Français des Porphyries, Hôpital Louis Mourier

Colombes, Cedex, 92701, France

Location

Department of Dermatology , Heinrich-Heine-University Duesseldorf

Düsseldorf, 40225, Germany

Location

Beaumont Hospital, Department of Dermatology

Dublin, 9, Ireland

Location

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

St Woolos Hospital

Newport, Wales, United Kingdom

Location

Photobiology Unit - Hope Hospital, University of Manchester

Manchester, M6 8HD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26132941 DERIVED

MeSH Terms

Conditions

Protoporphyria, Erythropoietic

Interventions

afamelanotide

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Porphyrias; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Operations Manager
• Organization: CLINUVEL PHARMACEUTICALS LTD

mail@clinuvel.com

Study Officials

• Alex Anstey, MBBS, FRCP

  St Woolos Hospital, Newport

  PRINCIPAL INVESTIGATOR

• Jorge Frank, MD, PhD

  Academisch Ziekenhuis Maastricht

  PRINCIPAL INVESTIGATOR

• Raili Kauppinen, MD, PhD

  University Central Hospital of Helsinki

  PRINCIPAL INVESTIGATOR

• Eric JG Sijbrands, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Jean-Charles Deybach, MD. PhD

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

  PRINCIPAL INVESTIGATOR

• Sandra Hanneken, MD

  Heinrich-Heine Universität, Düsseldorf, Germany

  PRINCIPAL INVESTIGATOR

• Gillian M Murphy, MD PhD

  Beaumont Hospital, Dublin, Ireland

  PRINCIPAL INVESTIGATOR

• Lesley E Rhodes, MD PhD

  Hope Hospital, University of Manchester, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 18, 2009
• Study Start: September 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: October 12, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-09

Locations

IE (1); FR (1); NL (2); FI (1); GB (2); DE (1)