A Randomized, Double-blind, Placebo-controlled, Parallel-group, Study to Assess the Safety and Efficacy of UX007 in Subjects With Glucose Transporter Type 1 Deficiency Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 14
- 主要终点
- Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
研究概览
简要总结
The primary objectives of the study are to evaluate the efficacy of UX007 compared to placebo as measured by the reduction from randomization to Week 8 in frequency of seizures and to evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG).
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
- 1 Year 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Glut1 DS confirmed by SLC2A1 mutation
- •Males and females at least 1 of age at the time of informed consent
- •Average of at least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, absence, or secondarily generalized seizures) in 4 weeks over the last 24 weeks, by subject or caregiver report
- •At least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, or secondarily generalized seizures) in 4 weeks during the Baseline Period, with no 3-week seizure-free period during the Baseline Period OR absence seizures documented on Screening electroencephalogram (EEG)
- •Continuing to have seizures despite a prior or current use of at least 1 antiepileptic drug (AED)
- •Allowed to be on up to 3 concomitant AEDs that must have been stable in dose at least 2 weeks prior to the beginning of screening and anticipated to remain stable in dose through the end of the 8-week, placebo-controlled Treatment Period
- •Not on, or not fully compliant with a prescribed diet plan (e.g. KD)
- •Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening
- •Provide written or verbal assent (if possible) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
- •Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, comply with accurate completion of the seizures diary, and likely to complete the 8 week, placebo-controlled, Treatment Period
- •Females of childbearing potential must have a negative pregnancy test at Screening, be willing to use an acceptable method of contraception, and have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not reached menarche, had total hysterectomy, have been in menopause for at least two years, or have had tubal ligation at least one year prior to Screening.
排除标准
- •Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 3 times the upper limit of normal at Screening
- •Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the investigator, places the subject at increased risk for adverse effects
- •Prior use of triheptanoin within 30 days prior to Screening
- •History of, or current suicidal ideation, behavior and/or attempts
- •Pregnant and/or breastfeeding an infant at Screening
- •Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives
- •Use of any investigational product (drug or supplement, including medium chain triglyceride [MCT] oil) within 30 days prior to Screening, or at any time during the study
- •Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment
- •Has a concurrent disease or condition, or laboratory abnormality that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns (e.g., diabetes mellitus, other concurrent neurological or psychiatric disorders)
研究组 & 干预措施
UX007
Participants randomized to receive UX007 enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period.
Following completion of the Week 8 study visit, participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
干预措施: UX007 (Drug)
Placebo
Participants randomized to receive placebo enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period.
Following completion of the Week 8 study visit, placebo participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
时间窗: Baseline, Week 8
Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (\>=10 sec), absence sleep (\>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period
时间窗: Weeks 0 to 8
An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period
时间窗: Weeks 9 to 52 plus 30 days
An AE was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
次要结局
- Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)(Baseline, Week 8)
- Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)(Baseline, Week 8)
- Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures(Baseline, Week 8)
- Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures(Baseline, Week 8)
- Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures(Baseline, Week 8)
- Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE(Baseline, Week 8)
- Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE(Baseline, Week 8)
- Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE)(Baseline, Week 8)
- Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT(Baseline, Week 8)
- Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8(Baseline, Week 4, Week 8)
- Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE(Baseline, Week 8)
- Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT)(Baseline, Week 8)
- Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score(Baseline, Week 8)
- Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate)(Baseline, Week 26, Week 31)
- Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate)(Baseline, Week 26, Week 31, Week 36, Week 52)
- Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate)(Baseline, Week 26, Week 31)