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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 6
- 主要终点
- Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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).
研究组 & 干预措施
Afamelanotide
Dose: 16 mg implant; release of 16 mg over 7 to 10 days Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120)
干预措施: Afamelanotide (Drug)
Placebo
Dose: 16 mg implant; Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120)
干预措施: Placebo (Drug)
结局指标
主要结局
Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days
时间窗: Daily for 6 months
The amount of direct sunlight exposure between 10:00 and 15:00 hours on days when no pain was experienced (e.g. 11-point Likert pain score of 0). Time was recorded in a patient dairy using 15 minute time blocks. The pain score is measured by the 11-point Likert Pain scale with minimum of 0 and maximum of 10. Likert Pain scale of 0 represents no pain and 10 represents worst imaginable pain.
次要结局
- Maximum Severity of Phototoxic Reaction Experienced by Participants(Daily for 6 months)
- Quality of Life Measured by Participant Completed Questionnaire(Day 0, Day 60, Day 120, Day 180)
- Change of Total Protoporphyrin IX Level in Participants(Baseline, Day 60, Day 120, Day 180)
- Number of Participants With Phototoxic Reactions With Likert Severity Scores ≥ 4 and ≥ 7(Daily for 6 months)
- Number of Phototoxic Reactions Experienced by Participants(Daily for 6 months)
- Total Severity of Phototoxic Reactions Experienced by Participants Over the Entire Study(Daily for 6 months.)