Phase III Confirmatory Study in Erythropoietic Protoporphyria
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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)|
- 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 ] [ Designated as safety issue: No ]
- Combined sun exposure and phototoxic pain [ Time Frame: 6 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.
- Quality of life [ Time Frame: 6 months ] [ Designated as safety issue: No ]Assessed by the DLQI and EPP-QoL measured at baseline and on Days 60, 120 and 180.
- Photoprovocation [ Time Frame: 6 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||April 2013|
|Estimated Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
One 16mg subcutaneous implant every 2 months for 6 months.
|Placebo Comparator: Placebo||
One placebo subcutaneous implant every 2 months for 6 months
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.
|United States, Alabama|
|University of Alabama|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|United States, Michigan|
|Henry Ford Medical Center|
|Detroit, Michigan, United States, 48202|
|United States, New York|
|New York, New York, United States, 10029|
|United States, North Carolina|
|Carolina's Medical Center Cannon Research|
|Charlotte, North Carolina, United States, 29203|
|United States, Texas|
|University of Texas|
|Galveston, Texas, United States, 77555|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Robert Desnick, MD||Mt. Sinai Medical Center|