Effects of N-Acetyl-L-Leucine on GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease): A Multinational, Multicenter, Open-label, Rater-blinded Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- IntraBio Inc
- 入组人数
- 30
- 试验地点
- 8
- 主要终点
- Clinical Impression of Change in Severity (CI-CS) [Fields et al 2021]
研究概览
简要总结
This is a multinational, multicenter, open-label, rater-blinded prospective Phase II study which will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease).
There are two phases to this study: the Parent Study, and the Extension Phase.
The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) in the symptomatic treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease).
The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of GM2 Gangliosidosis. The Extension Phase was considered exploratory.
详细描述
In the Parent Study, Patients will be assessed during three study phases: a baseline period, a 6-week treatment period, and a 6-week post-treatment washout period. If within 6 weeks prior to the initial screening visit, a patient has received any of the prohibited medications defined in the eligibility criteria (irrespective of the preceding treatment duration) a wash-out study-run-in of 6 weeks is required prior to the first baseline assessment. All patients will receive the study drug during the treatment period. For each individual patient, the Parent Study lasts for approximately 3.5 - 4 months during which there are 6 visits to the study site.
This Extension Phase allows patients who have completed the Parent Study to, at the discretion of the Principal Investigator (PI), continue treatment with N-Acetyl-L-Leucine (IB1001). Patients will receive treatment with IB1001 for two one-year treatment periods, separated by a 6-week washout. All patients will receive the study drug during these two one-year treatment periods. For each individual patient, the Extension Phase lasts for approximately 25.5 months, during which there are 6 visits to the study site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The primary evaluation of the Clinical Impression of Change in Severity (CI-CS; Primary Endpoint) will be performed by two independent neurologists whose assessments are based on videos of patient's performance on either the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or the 8 Meter Walk Test (8MWT) taken at each visit.
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment with IB1001
Parent Study: 6-weeks treatment with IB1001 administered orally. Extension Phase: 1-year treatment with IB1001 administered orally.
Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day).
Patients 6-12 years old will receive weight-tiered doses:
- Patients aged 6-12 years weighing 15 to <25 kg will take 2 g per day: 1 g in the morning and 1 g in the evening.
- Patients aged 6-12 years weighing 25 to <35 kg will take 3 g per day: 1 g in the morning, 1 g in the afternoon, and 1 g in the evening.
- Patients aged 6-12 years weighing ≥35 kg will take 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults)
干预措施: IB1001 (Drug)
结局指标
主要结局
Clinical Impression of Change in Severity (CI-CS) [Fields et al 2021]
时间窗: (CI-CS comparing Baseline [Day 1] with IB1001 versus the end of 6-weeks treatment with IB1001 [approximately Day 42]) MINUS (CI-CS comparing the end of 6-weeks treatment with IB1001 [approximately Day 42] versus end of 6-weeks post-treatment washout);
The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or 8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video? The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse). Change values were calculated for each period, i.e. treatment with IB1001 (comparing the end of treatment (Visit 4) with baseline (Visit 2)) and post-treatment washout (comparing the end of washout (Visit 6) with the end of treatment (Visit 4)). Then, the mean change obtained in the post-treatment period was subtracted from the mean change obtained for the treatment with IB1001 period, with a positive value indicating an improvement in the treatment period compared to the post-treatment washout period.
次要结局
- Key Secondary Endpoint: Change in Severity Based on Average CI-S((CI-S comparing baseline period [average for Visit 1 and 2] and end of treatment period [average for Visit 3 and 4]) minus (change in CI-S between end of treatment period [average for Visit 3 and 4] and end of washout period [average for Visit 5 and 6]).)
- Scale for Assessment and Rating of Ataxia (SARA) Score [Schmitz-Hübsch Etal, 2006; Subramony, 2007](Baseline to end of treatment with IB1001 (Parent Study Day 42); End of treatment with IB1001 to the end of post treatment washout)
- Key Secondary Endpoint: Individual Components of the CI-CS(Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout.)
- Key Secondary Endpoint: CI-CS Score for the Non-Primary Anchor Test(CI-CS of the non-primary anchor test was evaluated, comparing the CI-CS of Visit 4 (end of treatment) versus Visit 2 (baseline) and of Visit 6 (end of washout) versus Visit 4 (end of treatment) as done for the primary anchor test.)
- Parent/Caregiver's Clinical Global Impression of Change (CGI-C)(Baseline to end of treatment with IB1001 (Parent Study 6-week treatment); End of treatment with IB1001 to the end of post treatment washout)
- Key Secondary Endpoint: CI-CS Score Reclassified on a 3-Point Scale(Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout)
- EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale: Visual Analogue Scale (VAS)(Baseline to end of treatment with IB1001 (Parent Study 6-week treatment): observed VAS values at visit 4; End of treatment with IB1001 to the end of post treatment washout: observed VAS values at visit 6.)
- Spinocerebellar Ataxia Functional Index (SCAFI) [Schmitz-Hübsch et al, 2008](Change values were calculated for each period, i.e. treatment with IB1001 (comparing the end of treatment (Visit 4) with baseline (Visit 2)) and post-treatment washout (comparing the end of washout (Visit 6) with the end of treatment (Visit 4)).)
- Modified Disability Rating Scale (mDRS) [Iturriaga et al. 2006](Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post treatment washout.)
- Investigator's Clinical Global Impressions of Change (CGI-c)(Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post treatment washout.)
- Patient's Clinical Global Impressions (CGI) if Able(Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post treatment washout.)