A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- ApoPharma
- 入组人数
- 89
- 试验地点
- 4
- 主要终点
- Score on Patient Global Impression of Improvement at End of Study
研究概览
简要总结
A multi-center, placebo controlled, double-blind trial comparing the efficacy and safety of 18 months of treatment with deferiprone versus placebo in patients with PKAN.
This investigator-initiated trial was funded by the European Commission's Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984) to the TIRCON consortium (Treat Iron-Related Childhood-Onset Neurodegeneration) and by the FDA Office of Orphan Products Development (OOPD) (Dr. Elliott Vichinsky).
详细描述
This is a multi-center, double-blind, randomized, placebo-controlled, 18-month study in patients with PKAN aged 4 years and older. Participants are randomized in a 2:1 ratio to receive either deferiprone oral solution or placebo, twice a day for 18 months. Efficacy assessments, an MRI scan to measure iron levels in the globus pallidus, pharmacokinetic evaluations, and safety assessments are conducted at specified time points. Following completion of the trial, eligible patients are invited to enroll in an 18-month extension study, TIRCON2012V1-EXT, in which all participants receive deferiprone.
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)
盲法说明
Placebo solution matched deferiprone oral solution in appearance, taste, and packaging
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females 4 years of age and older at screening visit;
- •Have PKAN, confirmed by genetic testing (supporting evidence required);
- •Barry-Albright Dystonia (BAD) total score ≥ 3 at the screening visit;
- •Patients who have Deep Brain Stimulation (DBS) systems or baclofen pumps in place will be eligible for the study, but they must have had a stable setting for at least two months prior to the screening visit and stimulation parameters / pump settings must remain stable for the duration of the trial:
排除标准
- •Evidence of iron deficiency defined by Fe:TIBC ratio <15%, or serum ferritin <12 ng/mL;
- •Treatment with deferiprone in the past 12 months;
- •Previous failure of treatment with deferiprone, or previous discontinuation of treatment with deferiprone due to adverse events;
- •Conditions known to contraindicate the use of deferiprone (history of agranulocytosis or recurrent episodes of neutropenia);
- •A serious, unstable chronic illness not related to PKAN condition during the past 3 months before screening visit including but not limited to: hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease;
- •Evidence of abnormal liver or renal function (serum liver enzyme level(s) > 3 times upper limit of normal at screening) or abnormal creatinine levels at screening visit;
- •Disorders associated with neutropenia (ANC < 1.5 x 10^9/L) or thrombocytopenia (platelet count < 50 x 10^9/L) in the 12 months preceding the initiation of the study medication. Exception: for patients whose neutropenia was attributed by the treating physician to episodes of infection or to drugs associated with a decline in the neutrophil count and in whom the ANC has fully recovered at the screening visit;
- •History of malignancy;
- •Other protocol inclusion or exclusion criteria may apply.
研究组 & 干预措施
Deferiprone
Deferiprone 80 mg/mL oral solution
干预措施: Deferiprone oral solution (Drug)
Placebo
Matching placebo solution
干预措施: Placebo (Drug)
结局指标
主要结局
Score on Patient Global Impression of Improvement at End of Study
时间窗: Month 18
The Patient Global Impression of Improvement (PGI-I) is a global index that assesses the response of a condition to a therapy by asking patients to rate their current state relative to their state at baseline. It consists of a 7-point rating scale, where 1=very much improved, 2= much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Change in Score on Barry-Albright Dystonia Scale
时间窗: Baseline to 18 Months
The Barry-Albright Dystonia (BAD) scale rates severity of dystonia (sustained muscle contractions causing twisting and repetitive movements or abnormal postures) in 8 body regions. The individual scores are summed to provide a total score ranging from 0 to 32, with higher scores indicating greater severity. The co-primary endpoint in this study was the change from baseline to Month 18 in BAD total score.
次要结局
- Change in Score on WeeFIM(Baseline to 18 Months)
- Change in Score on Pediatric Quality of Life(Baseline to 18 Months)
- Change in Score on Unified Parkinson's Disease Rating Scale(Baseline to 18 Months)
- Change in Score on Functional Independence Measure(Baseline to 18 Months)
- Change in Score on Pittsburgh Sleep Quality Index(Baseline to 18 Months)
- Change in Level of Brain Iron(Baseline to 18 Months)