Clinical trial NCT01097044: Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)
Official title: A Phase II, 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Erythropoietic Protoporphyria
Keywords: Erythropoietic Protoporphyria
EPP
Afamelanotide
Lead sponsor: Clinuvel Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2010-04-01
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized placebo-controlled study to be conducted in two parallel study arms for a six month period (three doses). Approximately 10 eligible patients per center will be enrolled and 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

To determine eligibility for study inclusion, patients will undergo a screening evaluation 7 to 14 days prior to the administration of the first dose. The number and severity of phototoxic reactions will be determined Days 60, 120, and 180. Quality of life will be measured using the EPP specific questionnaire (EPP-QoL) every 60 days and the DLQI questionnaire every 7 days, beginning at Day 0 until Day 180. Participants will visit the clinic on Days 60, 120 and 180 for assessments of adverse events.

Detailed description: 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 between 10:00 and 20:00 hours. 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 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.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects with characteristic photosensitivity of EPP symptoms and positive diagnosis of EPP confirmed by laboratory result of elevated total protoporphyrin IX.
* 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 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 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 within 60 days prior to the screening visit.
* 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).

Primary outcomes:
measure: Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days
timeFrame: Daily for 6 months
Secondary outcomes:
measure: Maximum Severity of Phototoxic Reaction Experienced by Participants
timeFrame: Daily for 6 months
measure: Quality of Life Measured by Participant Completed Questionnaire
timeFrame: Day 0, Day 60, Day 120, Day 180
measure: Change of Total Protoporphyrin IX Level in Participants
timeFrame: Baseline, Day 60, Day 120, Day 180
measure: Number of Participants With Phototoxic Reactions With Likert Severity Scores ≥ 4 and ≥ 7
timeFrame: Daily for 6 months
measure: Number of Phototoxic Reactions Experienced by Participants
timeFrame: Daily for 6 months
measure: Total Severity of Phototoxic Reactions Experienced by Participants Over the Entire Study
timeFrame: Daily for 6 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New York
country: United States
facility: Mt. Sinai
state: New York
city: Charlotte
country: United States
facility: Carolina's Medical Center Cannon Research
state: North Carolina
city: Galveston
country: United States
facility: University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Mt. Sinai
name: Robert Desnick, MD
role: PRINCIPAL_INVESTIGATOR
References: