Phase III Confirmatory Study in Erythropoietic Protoporphyria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01605136
Recruitment Status : Unknown
Verified March 2013 by Clinuvel Pharmaceuticals Limited.
Recruitment status was:  Active, not recruiting
First Posted : May 24, 2012
Last Update Posted : March 22, 2013
Information provided by (Responsible Party):
Clinuvel Pharmaceuticals Limited

May 22, 2012
May 24, 2012
March 22, 2013
May 2012
April 2013   (Final data collection date for primary outcome measure)
Duration of direct sunlight exposure between 10:00 and 18:00 hours on days when no pain was experienced (pain score of 0). [ Time Frame: 6 months ]
Same as current
Complete list of historical versions of study NCT01605136 on Archive Site
  • Combined sun exposure and phototoxic pain [ Time Frame: 6 months ]
    Duration of direct sunlight exposure between 10:00 and 18:00 hours on days when no or mild pain was experienced (Likert scores of 0 to 3).
  • Sun exposure [ Time Frame: 6 months ]
    Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.
  • Quality of life [ Time Frame: 6 months ]
    Assessed by the DLQI and EPP-QoL measured at baseline and on Days 60, 120 and 180.
  • Photoprovocation [ Time Frame: 6 months ]
    A subset of patients will be photoprovoked on the lower back and dorsal surface of the hand to determine the minimum symptom dose on Days 0, 30, 60, 90 and 120.
  • Phototoxicity - phototoxic pain [ Time Frame: 6 months ]

    The maximum and total pain severity scores (Likert scale) for phototoxic episodes.

    The number of phototoxic episodes reported from Day 0 to Day 180.

  • Safety and Tolerability Endpoints [ Time Frame: 6 months ]
    Treatment-emergent adverse events (coded as MedDRA Preferred Terms). Changes in hematology, serum chemistry, urinalysis, physical examination and vital sign measurements from Screening to Study Days 60, 120, 180, and at Early Termination Visit, if applicable.
Same as current
Not Provided
Not Provided
Phase III Confirmatory Study in Erythropoietic Protoporphyria
A Phase III, Multicentre, Double-Blind, Randomized, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)

This is a randomized placebo-controlled study to be conducted in two parallel study arms for a six month period (three doses). Between 75 and 100 eligible patients will be enrolled. Patients will receive afamelanotide (16 mg implants) or placebo according to the following dosing regimen:

  • Group A will be administered afamelanotide implants on Days 0, 60 and 120
  • Group B will be administered placebo implants on Days 0, 60 and 120

The number and severity of phototoxic reactions, the type and duration of sun exposure, treatment-emergent adverse events and the use of concomitant medication will be recorded by patients in study diaries between Days 0 and 180. Quality of life will be measured using the DLQI and EPP-QoL at Days 0, 60, 120 and 180. Participants will visit the clinic on Days 60, 120 and 180 for assessments of adverse events.

A subset of patients will be photoprovoked on the lower back and dorsal surface of the hand and the minimal symptom dose (MSD) will be determined on Days 0, 30, 60, 90 and 120.

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) 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 to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).

Over 620 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.

This study aims to confirm the photoprotective properties if afamelanotide demonstrated in the earlier Phase II and phase III studies.

Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Erythropoietic Protoporphyria
  • Drug: Afamelanotide
    One 16mg subcutaneous implant every 2 months for 6 months.
  • Drug: Placebo
    One placebo subcutaneous implant every 2 months for 6 months
  • Experimental: Afamelanotide
    Intervention: Drug: Afamelanotide
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Unknown status
April 2013
April 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female subjects with characteristic symptoms of EPP phototoxicity and a biochemically-confirmed diagnosis of EPP.
  • Aged 18 years old and above (inclusive).
  • Able to understand and sign the written Informed Consent Form.
  • Willing to take precautions to prevent pregnancy until completion of the study (Day 180).

Exclusion Criteria:

  • Any allergy to afamelanotide or the polymer contained in the implant or to lidocaine or other local anesthetic 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 polymorphic light eruption, actinic prurigo, discoid lupus erythematosus, chronic actinic dermatitis 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 6 months).
  • Patient assessed as not suitable for the study in the opinion of the Investigator (e.g. noncompliance history, allergic to local anesthetics, faints when given injections or giving blood).
  • Participation in a clinical trial for 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.
  • 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).
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Clinuvel Pharmaceuticals Limited
Clinuvel Pharmaceuticals Limited
Not Provided
Principal Investigator: Robert Desnick, MD Mt. Sinai Medical Center
Clinuvel Pharmaceuticals Limited
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP