Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin: An Open-label, 10-subject Clinical Trial of UX007 (Triheptanoin) in the Treatment of Mitochondrial Dysfunction in Participants With Rett Syndrome, Dyskinesia, and Epilepsy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change in Dystonia frequency
研究概览
简要总结
The aim of this study is to evaluate the safety and tolerability of triheptanoin in participants with Rett syndrome using laboratory values, electrocardiogram, rate of adverse events (AE), and physical exam.This study also seeks to evaluate the efficacy of UX007 (triheptanoin) in improving overall seizure frequency and dystonia.
详细描述
The aim of this study is to evaluate the safety and tolerability of triheptanoin in participants with Rett syndrome using laboratory values, electrocardiogram, rate of adverse events (AE), and physical exam. This study also seeks to evaluate the efficacy of UX007 (triheptanoin) in improving overall seizure frequency, dystonia severity, and quality of life. Participants who are eligible will take triheptanoin daily. Participation in the primary arm of this study will last up to 8.5 months, with an optional 36 month extension.
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
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Classic Rett syndrome as defined by the clinical consensus criteria
- •Presence of a MECP2 mutation
- •Post-regression stage of development, defined as greater than 6 months since the last loss of hand use or verbal language
- •Average of at least 4 observable seizures (generalized or partial-onset [Generalized Tonic-Clonic, Generalized Tonic, Generalized Clonic, Generalized Atonic, Partial/Focal with Secondary Generalization, Myoclonic, Myoclonic Atonic, Myoclonic Tonic, Complex Partial/Focal, and Simple Partial/Focal Motor) in one month prior to the study by caregiver report or presence of dystonia on average at least four times in one month prior to the study in at least one body region rated as at least "mild" by caregiver report
- •Use of at least one anti-seizure medication at screening visit
- •At screening visit, managed on four or fewer concomitant anti-seizure medications that must have been stable in dose at least one month prior to the beginning of screening and anticipated to remain stable in dose through the end of the 8.5 month trial period
- •Legally authorized caregiver must be willing to give written informed consent after the nature of the study has been explained, and prior to any research-related procedures
- •Caregiver and participant must, in the opinion of the investigator, be willing and able to complete all aspects of the study, comply with accurate completion of the seizure and dystonia diaries, and be likely to complete the four month treatment period
排除标准
- •Markedly abnormal metabolic screening laboratory testing (e.g., serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2X the upper limit of normal)
- •Any known hypersensitivity to triheptanoin that, in the judgment of the investigator, places the subject at increased risk for adverse effects
- •Prior use of triheptanoin within 1 month prior to screening
- •Participants or caregivers who are unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives
- •Use of any other investigational product, including drugs or supplements within 1 month 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)
- •Pregnant or nursing women
研究组 & 干预措施
Participants aged 0 months to 3 years
Participants will receive 4 grams of triheptanoin per kilogram of body weight daily.
干预措施: triheptanoin (Drug)
Participants aged 4 to 6 years
Participants will receive 3 grams of triheptanoin per kilogram of body weight daily.
干预措施: triheptanoin (Drug)
Participants aged 7 to 9 years
Participants will receive 2.5 grams of triheptanoin per kilogram of body weight daily.
干预措施: triheptanoin (Drug)
Participants aged 10 to 14 years
Participants will receive 2 grams of triheptanoin per kilogram of body weight daily.
干预措施: triheptanoin (Drug)
Participants aged 15 to 20 years
Participants will receive 1.5 grams of triheptanoin per kilogram of body weight daily.
干预措施: triheptanoin (Drug)
Participants aged 21 years and older
Participants will receive 1.2 grams of triheptanoin per kilogram of body weight daily.
干预措施: triheptanoin (Drug)
结局指标
主要结局
Change in Dystonia frequency
时间窗: Visit 2, Visit 7 (Up to 4 months)
The frequency of dystonic posturing present in each limb recorded via caregiver-reported diary on each day of treatment between Visit 2 and Visit 7 of treatment.
Change in Clinical Seizure Frequency
时间窗: Visit 2, Visit 7 (Up to 4 months)
The number of observable seizures recorded via caregiver-reported diary between Visit 2 and Visit 7 of treatment.
次要结局
- Change in the PROMIS Fatigue Parent Proxy Score(Visit 2, Visit 7 (Up to 4 months))
- Change in the PROMIS Pain Interference Parent Proxy Score(Visit 2, Visit 7 (Up to 4 months))
- Change in the PROMIS Peer Relations Parent Proxy Score(Visit 2, Visit 7 (Up to 4 months))
- Change in Dystonia Severity(Visit 1, Visit 7 (Up to 4 months))
- Change in Burke-Fahn-Marsden Dystonia Rating Scale (BFM) Score(Visit 1, Visit 9 (Up to 8.5 months))
- Change in Global Dystonia Rating Scale (GDRS) Score(Visit 1, Visit 9 (Up to 8.5 months))
- Change in the PROMIS Physical Functional Mobility Parent Proxy Score(Visit 2, Visit 7 (Up to 4 months))
- Change in the PROMIS Anxiety Parent Proxy Score(Visit 2, Visit 7 (Up to 4 months))
- Change in the PROMIS Depressive Symptoms Parent Proxy Score(Visit 2, Visit 7 (Up to 4 months))
- Change in Child Health Questionnaire-50 (CHQ) Score(Visit 2, Visit 7 (Up to 4 months))
- Change in the Clinician Clinical Global Impression - Improvement Scale (CGI-S) Score(Visit 2, Visit 9 (Up to 8.5 months))
- Change in the Clinician Clinical Global Impression - Severity Scale Score(Visit 2, Visit 9 (Up to 8.5 months))
- Change in the Parental Clinical Global Impression of Improvement Score(Visit 2, Visit 9 (Up to 8.5 months))
- Change in Parent Top Three Concerns Visual Analog Scale Ranking(Visit 2, Visit 9 (Up to 8.5 months))
- Change in the PROMIS Physical Function Upper Extremity Parent Proxy Score(Visit 2, Visit 7 (Up to 4 months))
- Change in the Clinical Severity Scale (CSS) Score(Visit 1, Visit 9 (Up to 8.5 months))
- Seizure Activity assessed by Change in Electrodermal Activity (EDA)(Visit 1, Visit 9 (Up to 8.5 months))
- Change in the Motor Behavioral Assessment (MBA) Score(Visit 1, Visit 9 (Up to 8.5 months))
- Change in the Rett Syndrome Behavioural Questionnaire (RSBQ) Score(Visit 1, Visit 9 (Up to 8.5 months))
- Change in the Rett Syndrome Hand Apraxia Scale (RHAS) Score(Visit 1, Visit 9 (Up to 8.5 months))
- Change in the Rett Syndrome Gross Motor Scale (RSGMS) Score(Visit 1, Visit 9 (Up to 8.5 months))
- Change in Maximum Heart Rate as assessed by the Graded Maximal Treadmill Test(Visit 1, Visit 9 (Up to 8.5 months))
- Change in Maximum Speed Acheived as assessed by the Graded Maximal Treadmill Test(Visit 1, Visit 9 (Up to 8.5 months))
- Frequency of Epileptiform Electroencephalogram (EEG) Activity(Visit 1, Visit 7 (Up to 6.5 months))
- Seizure Activity assessed by Change in Photoplethysmographic Heart Rate(Visit 1, Visit 9 (Up to 8.5 months))
- Change in Daily 3-axis accelerometry(Visit 1, Visit 9 (Up to 8.5 months))
- Seizure Activity assessed by Change in Skin Temperature(Visit 1, Visit 9 (Up to 8.5 months))
研究者
Daniel C. Tarquinio
Managing Director
Center for Rare Neurological Diseases, Norcross, GA