A Phase 1b/2 Open-label Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy Following Fosigotifator Administration in Adult and Pediatric Subjects With Vanishing White Matter Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- Incidence of Treatment-Emergent Adverse Events
研究概览
简要总结
Fosigotifator is an investigational drug being researched for the treatment of Vanishing White Matter disease in adult, pediatric and infant participants. This is a 201-week, open-label, multiple cohort study enrolling adults, pediatric and infant participants with Vanishing White Matter disease.
Participants will attend regular visits during the course of the study and complete medical assessments, blood tests, questionnaires, and be evaluated for side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females >= 6 months of age at the time of Screening.
- •Have VWM disease defined as:
- •A clinical diagnosis by a physician experienced in the assessment of VWM disease; and
- •A molecular diagnosis of VWM disease, and
- •A magnetic resonance imaging (MRI) presentation consistent with VWM disease.
- •Have a designated caregiver who is able to complete the respective caregiver-centered assessments.
- •Signed and dated informed consent provided by the participant, or from a legally authorized representative (LAR) if participant is incapable to consent themselves.
- •Participants must meet criteria (a) and at least one of the following functional criteria (b or c):
- •Medical history of at least 1 neurological symptom that is assessed by the investigator as having a reasonable possibility of being related to VWM disease.
- •Motor criteria defined as inability to walk 10 or more steps with or without light support of 2 hands
- •Cognitive criteria as assessed by the age-appropriate version of the Wechsler Intelligence Scale, with participants scoring < 50 on specific indices; specific details can be provided by the Study physician.
- •Pediatric participants in Cohort 4 must meet both criteria a and b below, or criterion c:
- •Medical history of at least 1 neurological symptom that is assessed by the investigator as having a reasonable possibility of being related to VWM disease.
- •Motor criteria as defined below:
- •i. More than minimal head control as demonstrated by: While in prone position, the participant can lift his/her head and sustain the position for 10 seconds and bring his/her arms actively to weight bearing in that position.
- •c. Presymptomatic and homozygous for Cree Leukoencephalopathy (EIF2B5 R195H) or other mutation with known imminent risk of significant clinical decline or death (sponsor must be notified and provide approval prior to screening and enrolling a participant that meets eligibility with only this criterion).
- •All male participants who are sexually active and not surgically sterilized must agree to use an acceptable contraceptive method. Additionally, male participants must agree to not donate sperm during the study until 30 days after the final dose of study drug.
- •All female participants who are sexually active and of childbearing potential must agree to use a highly effective contraceptive method. Additionally, female participants must agree to not donate eggs during the study and for 30 days after the final dose of study drug.
排除标准
- •Pediatric participants >= 6 months and < 6 years of age must not be on any form of respiratory support at the time of Screening.
- •Changes in medication use for the management of VWM disease symptoms within the 4 weeks preceding Screening.
- •Seizure disorder not considered adequately controlled by the investigator within the 6 months preceding Screening.
- •Participant who, in the opinion of the investigator, is incapable of completing study-required visits and procedures to assess primary and secondary endpoints.
- •Adult female participants who are pregnant, breastfeeding or providing breast milk.
- •Treatment with any other investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to Baseline.
- •Any clinically significant laboratory or imaging findings at Screening.
研究组 & 干预措施
Fosigotifator - Cohort 3
Cohort 3: VWM children >= 6 y and <12 years.
干预措施: Fosigotifator (Drug)
Fosigotifator - Cohort 2
Cohort 2: VWM children>= 12 y and <18 years.
干预措施: Fosigotifator (Drug)
Fosigotifator - Cohort 1
Cohort 1: VWM adults >= 18 years.
干预措施: Fosigotifator (Drug)
Fosigotifator - Cohort 1b
Cohort 1b: VWM adults >= 18 years.
干预措施: Fosigotifator (Drug)
Fosigotifator - Cohort 4
Cohort 4: VWM children >= 6 months and <6 years.
干预措施: Fosigotifator (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events
时间窗: Baseline up to Approximately Day 28
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Number of Participants with Change in Vital Signs
时间窗: Baseline up to Approximately Day 28
Number of Participants with Change in Vital Signs will be assessed.
Number of Participants with Change in ECG
时间窗: Baseline up to Approximately Day 28
Number of Participants with Change in ECG will be assessed.
Number of Participants with Change in Clinical Laboratory Tests
时间窗: Baseline up to Approximately Day 28
Number of participants with change in clinical laboratory tests will be assessed.
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Baseline up to Approximately Day 28
The C-SSRS is a systematically administered instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.
Plasma Concentration of Fosigotifator
时间窗: Baseline up to approximately Week 96
Maximum Plasma Concentration \[Cmax\]
Time to Cmax (Tmax) of Fosigotifator
时间窗: Baseline up to approximately Week 96
Tmax of Fosigotifator
Area Under the Plasma Concentration-Time Curve (AUC0-24h) of Fosigotifator
时间窗: Baseline up to approximately Week 96
AUC0-24h of Fosigotifator
Trough Concentration (Ctrough) of Fosigotifator
时间窗: Baseline up to approximately Week 96
Ctrough of Fosigotifator
Terminal Elimination Half-Life (t1/2) of Fosigotifator
时间窗: Baseline up to approximately Week 96
t1/2 of Fosigotifator
次要结局
- Incidence of Treatment-Emergent Adverse Events(Baseline up to Approximately Week 197)
- Number of Participants with Change in Vital Signs(Baseline up to approximately Week 197)
- Number of Participants with Change in ECG(Baseline up to approximately Week 197)
- Number of Participants with Change in Clinical Laboratory Tests(Baseline up to approximately Week 197)
- Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline up to approximately Week 197)
- Number of Participants with Change in Magnetic Resonance Imaging (MRI)(Baseline up to approximately Week 192)