A Phase III, Multicentre, Randomised, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutanenous Bioresorbable CUV1647 Implants in Patients With Erythropoietic Protoporphyria (EPP)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 100
- 主要终点
- The Mean Number of Phototoxic Reactions (Study Efficacy Population)
研究概览
简要总结
This was a phase III, multicentre, randomised, double-blind, placebo-controlled study, to evaluate the safety and efficacy of subcutaneous bioresorbable afamelanotide implants in patients with Erythropoietic Protoporphyria (EPP).
The study was conducted with two parallel study arms with crossover between treatments every 60 days.
Eligible patients were randomised to a treatment group, and received implants of active treatment (afamelanotide 16mg) or placebo, in an alternating crossover fashion according to the following dosing regime:
- Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300
- Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300
详细描述
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).
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).
This study aims to provide insight into the effectiveness of afamelanotide under normal conditions of use in EPP patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients 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.
- •Written informed consent prior to the performance of any study-specific procedure.
排除标准
- •Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic 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.
- •Diagnosed with HIV/AIDS or hepatitis.
- •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).
- •History of disorders of the gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine (including diabetes, Cushing's syndrome, Addison's disease, Peutz-Jeagher syndrome), neurological (including seizures), haematological (especially anaemia of less than 10 g/100 mL) or systemic disease judged to be clinically significant by the Investigator.
- •Major medical or psychiatric illness
- •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 was 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).
- •Participation in a clinical trial of an investigational agent within 30 days prior to the screening visit.
- •Use of regular medications as specified in protocol Section 5.4 Prior and Concomitant Therapy.
- •Any factors that may affect skin reflectance measurements.
研究组 & 干预措施
Group A
Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300
干预措施: Placebo (Drug)
Group B
Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300
干预措施: Placebo (Drug)
Group A
Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300
干预措施: Afamelanotide (Drug)
Group B
Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300
干预措施: Afamelanotide (Drug)
结局指标
主要结局
The Mean Number of Phototoxic Reactions (Study Efficacy Population)
时间窗: 0-360 days or Early Termination
The mean number of phototoxic reactions that occurred whilst patients were on active compared with placebo implants. The days on which the participant experienced pain as a result of phototoxic reactions (caused by exposure to natural light) was recorded in a study diary. On each day such a reaction occurred, the participant scored the level of pain using an 11-point Likert pain scale, with minimum of 0 and maximum of 10. The 11-point Likert pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain. The primary analysis population for efficacy was revised, to analyze only participants who reported a cumulative total Likert pain score of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis.
Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population)
时间窗: 0-360 days or Early Termination
The cumulative number of days where a phototoxic reaction occurred was recorded in the patient diary. The reported data represent a cumulative total for days of phototoxic reactions. The participant scored the level of pain using an 11-point Likert pain scale, with minimum of 0 and maximum of 10. The 11-point Likert Pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain. The primary analysis population for efficacy was revised, to analyze only participants who reported cumulative total Likert pain scores of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis.
次要结局
- Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population(Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination)
- Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population)(0-360 days or Early Termination)
- Skin Melanin Density (Study Completers Population)(Day0, Day14, Day30, Day60, Day74, Day90, Day120, Day150, Day180, Day210, Day240, Day270, Day300, Day330, Day360 or Early Termination)
- Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population(Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination)