NCT04378075终止2 期
Efficacy and Safety Study of Vatiquinone for the Treatment of Mitochondrial Disease Subjects With Refractory Epilepsy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 68
- 试验地点
- 27
- 主要终点
- Percent Change From Baseline to Week 24 in the Number of Observable Motor Seizures per 28 Days
研究概览
简要总结
This is a parallel-arm, double-blind, placebo-controlled study with a screening phase that includes a 28-day run-in phase to establish baseline seizure frequency, followed by a 24-week, randomized, placebo-controlled phase. After completion of the randomized, placebo-controlled phase, participants may enter a 48-week, long-term, extension phase during which they will receive open-label treatment with vatiquinone.
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
- — 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form.
- •Participant or parent/legal guardian is able and willing to complete seizure diaries for the duration of the study.
- •Genetic confirmation of inherited mitochondrial disease with associated epilepsy phenotype (Alpers/polymerase subunit gamma [POLG], Leigh syndrome, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [MELAS]), or other genetically confirmed mitochondrial disease secondary to mitochondrial mutations (Pontocerebellar Hypoplasia Type 6 [PCH6], nuclear DNA RARS2 mutation) or myoclonic epilepsy with ragged red fibers (MERRF, mitochondrial DNA [mtDNA] mitochondrially encoded tRNA lysine [MT-TK] mutation).
- •Despite ongoing treatment with at least 2 antiepileptic drugs:
- •have ≥6 observed motor seizures occurring during the 28 days prior to the baseline visit (Day 0).
- •have ≥2 observed motor seizures in the first 14 days and ≥2 in the second 14 days of the Run-in period (Day -14).
- •do not have a consecutive 20-day seizure free period.
- •have at least 80% of seizure diary data.
- •Documented medical history of epilepsy associated with mitochondrial disease for at least 6 months prior to screening except for participants who are <2 years of age at the time of screening (participants <2 years of age can be considered for enrollment if all other screening criteria are met due to the potential for rapid progression in these participants).
- •Consent to abstain from non-approved therapies for 30 days prior to the screening visit and for the duration of the study.
- •Stable dose regimen of antiepileptic therapies 30 days prior to the screening visit.
- •Stable regimen of dietary supplements 30 days prior and, if on a ketogenic diet, stable ketogenic diet 90 days prior to the screening visit and for duration of the study.
- •Electroencephalogram (EEG) at screening or historical EEG up to 6 months prior to screening for diagnostic confirmation of seizures.
排除标准
- •Allergy to vatiquinone or sesame oil.
- •Aspartate transaminase (AST) or alanine transaminase (ALT) ≥3 × upper level of normal (ULN) at time of screening.
- •International normalized ratio (INR) >ULN at time of screening.
- •Serum creatinine ≥1.5 × ULN at time of screening.
- •Participation in another interventional clinical trial 60 days prior to randomization or for the duration of this clinical trial
- •Previously received vatiquinone.
- •Concomitant treatment with drug(s) that have not received regulatory agency approval for the treatment of mitochondrial diseases and use of artisanal (non-Epidiolex cannabidiol) cannabidiol therapies.
- •Concomitant treatment with idebenone.
- •Ongoing treatment with strong cytochrome P450 (CYP) inhibitors such as itraconazole or strong CYP inducers such as rifampin. Treatment with these agents must be completed at least 4 weeks prior to enrollment.During the study, participants should not use grapefruit/grapefruit juice or St John's wort extract.
- •Pregnant or lactating participants or those male or female sexually active participants who are unwilling to comply with proper birth control methods from the time consent is signed until 30 days after treatment discontinuation. Females of childbearing potential must have a negative pregnancy test at screening and during the baseline visit (Day 0).
- •Comorbidities that may confound study results (for example, fat malabsorption syndrome, other mitochondrial disorders) in the opinion of the investigator.
研究组 & 干预措施
Vatiquinone
Experimental
15 milligrams/kilogram (mg/kg) if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, 3 times per day (TID) or up to 72 weeks
干预措施: Vatiquinone (Drug)
Vatiquinone
Experimental
15 milligrams/kilogram (mg/kg) if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, 3 times per day (TID) or up to 72 weeks
干预措施: Placebo (Other)
Placebo
Placebo Comparator
Vatiquinone-matching placebo, administered orally, TID for up to 24 weeks followed by vatiquinone 15 mg/kg if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, TID for up to 48 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Percent Change From Baseline to Week 24 in the Number of Observable Motor Seizures per 28 Days
时间窗: Day 0, Week 24
次要结局
- Number of Disease-Related Hospital Days(Week 24 and up to Week 72)
- Number of Participants with Occurrences or Recurrence of Status Epilepticus(Week 24 and up to Week 72)
- Number of Participants with Disease-Related In-Patient Hospitalizations or Emergency Room Visits(Week 24 and up to Week 72)
- Number of Disease-Related In-Patient Hospital Admissions or Emergency Room Visits(Week 24 and up to Week 72)
- Percent Change From Baseline to Week 72 in Total Seizure Frequency per 28 Days(Day 0, Week 24, Week 72)
- Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Motor Seizures(Week 24 and up to Week 72)
- Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Total Seizures(Week 24 and up to Week 72)
- Number of Participants Who Require Rescue Seizure Medication(Week 24 and up to Week 72)
- Health-Related Quality of Life as Measured by the Care-Related Quality of Life of Informal Caregivers (CarerQoL-7D) Questionnaire(Week 24 and up to Week 72)
- Number of Participants with Seizure Clusters(Week 24 and up to Week 72)
研究者
研究点 (27)
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