An Open-Label, Multicenter, Phase 2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PLX-200 in Pediatric Patients With Lysosomal Storage Disorders (SOTERIA)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 24
- 主要终点
- To evaluate the change from baseline in 12-lead electrocardiogram in study participants 2 to 15 years old with LSDs during the treatment period.
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and clinical activity of PLX-200 in pediatric patients with lysosomal storage disorders.
详细描述
This is an open-label, proof-of-concept, Phase 2 basket trial evaluating the safety, tolerability, and clinical activity of PLX-200 in pediatric participants with lysosomal storage disorders (LSDs) including CLN2, CLN3, Sandhoff disease, and Krabbe disease. Participants will receive PLX-200 oral solution twice daily (BID) for approximately 101 weeks, comprising of a 5-week Titration Period and 96-week Maintenance Period. Clinical activity will be evaluated using synthetic control comparisons. Dosing strategies and study durations for all other indications will be defined in their respective ISAs.
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 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged 2 to 15 years at the time of informed consent. Any deviations must be approved in advance by the Medical Monitor and Sponsor.
- •Genetically confirmed diagnosis of one of the four LSDs included in this study: CLN2, CLN3, Sandhoff disease or Krabbe disease. Diagnosis must be supported by all of the following:
- •Age of symptom onset consistent with the targeted subtype,
- •Relevant clinical manifestations, and
- •Documented genotype at Screening or prior to enrollment. If no genotype is available at Screening, blood samples will be collected for genetic analysis as part of study procedures.
- •Written informed consent must be obtained from the participant's parent(s) or legal guardian(s). Assent must also be obtained from the participant, when applicable, in accordance with local regulations and the participant's developmental status.
- •Parent(s) or legal guardian(s) must demonstrate willingness and ability to comply with the protocol, including adherence to all required baseline, treatment, and follow-up assessments.
排除标准
- •The participant has a known inherited neurologic disease other than the targeted lysosomal storage disorder subtype.
- •The participant has a neurological illness unrelated to the study indication that may independently cause cognitive or motor decline.
- •The participant requires ventilatory support, except for noninvasive support during sleep (e.g., Continuous Positive Airway Pressure [CPAP], Bilevel Positive Airway Pressure [BiPAP]).
- •The participant has moderate or severe hepatic dysfunction, defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin greater than 3 times the upper limit of normal (ULN), except in cases of Gilbert syndrome. The participant has a diagnosis of primary biliary cirrhosis.
- •The participant has clinically significant anemia
- •The participant has a body surface area (BSA)-adjusted eGFR <90 mL/min/1.73m2 at Screening or baseline.
- •The participant has a history or current diagnosis of gallbladder disease (e.g., cholelithiasis or cholecystitis).
- •The participant has a known hypersensitivity to gemfibrozil or any component of the study drug.
- •The participant is currently using, or is expected to require during the study, any of the following medications which are contraindicated with PLX-200:
- •HMG-CoA reductase inhibitors
- •Repaglinide (Prandin®)
- •Dasabuvir (Exviera®)
- •Selexipag (Uptravi®)
- •Pioglitazone (Actos®)
- •Fibrate medication (e.g., gemfibrozil, fenofibrate). Participants must not have received gemfibrozil or other fibrates for at least 2 weeks or five half-lives, whichever is shorter, before Visit 2 (Day 1). They may not receive gemfibrozil or other fibrates during the study
- •Participants receiving Zavesca® (miglustat) or any other prohibited therapies must be willing to discontinue these therapies, complete a washout period (2 weeks or five half-lives, whichever is shorter) prior to Visit 2 (Day 1), and refrain from receiving them while they are participating in the study. If participants were previously on Brineura®, they must complete a 3-month washout period prior to Visit 2 (Day 1) and refrain from receiving it while they are participating in the study.
- •The participant has a medical condition or personal circumstance that, in the opinion of the Investigator or Sponsor, could compromise safety, protocol compliance, or the interpretability of study data.
- •The participant has received any investigational product or medical device within 30 days prior to the baseline visit that could confound study results or pose additional risk. All participants who have previously received stem cell or gene therapy are excluded regardless of timing.
- •The participant receives systemic anticoagulant therapy (e.g., warfarin) and is unable or unwilling to comply with increased frequency of INR monitoring during study participation. Note: Participants may be eligible if receiving anticoagulants (e.g., warfarin) provided that INR can be monitored with increased frequency and dose adjustments are implemented to maintain therapeutic range and avoid bleeding complications.
- •The participant has uncontrolled seizures, defined as ≥4 generalized tonic-clonic seizures per month or a recent episode of status epilepticus.
- •The participant has severe central nervous system abnormalities (e.g., hydrocephalus, intracranial shunt).
- •The participant has a history of clinically significant arrhythmia or QTc prolongation at Screening or baseline.
- •The participant is pregnant or breastfeeding or is a female showing signs of pubertal development (e.g., Tanner Stage ≥2) who is unable or unwilling to undergo pregnancy testing at Screening or baseline. All such determinations must involve consultation with the Medical Monitor and follow the procedures outlined in each ISA.
研究组 & 干预措施
PLX-200 (CLN3 Disease Cohort)
An Open-Label, Multicenter, Phase 2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PLX-200 in Pediatric Patients with CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis) (CLN3 Intervention-Specific Assessment [ISA] Under the PLX-200-600 Master Protocol)
干预措施: PLX-200 (Drug)
PLX-200 (Sandhoff Disease Cohort)
An Open-Label, Multicenter, Phase 2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PLX-200 in Pediatric Patients with Sandhoff Disease (GM2 Gangliosidosis Type II) (Sandhoff Disease Intervention-Specific Assessment [ISA] Under the PLX-200-600 Master Protocol)
干预措施: PLX-200 (Drug)
PLX-200 (Krabbe Disease Cohort)
An Open-Label, Multicenter, Phase 2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PLX-200 in Pediatric Patients with Krabbe Disease (Globoid Cell Leukodystrophy) (Krabbe Disease Intervention-Specific Assessment [ISA] Under the PLX-200-600 Master Protocol)
干预措施: PLX-200 (Drug)
PLX-200 (CLN2 Disease Cohort)
An Open-Label, Multicenter, Phase 2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PLX-200 in Pediatric Patients with CLN2 Disease (Late-Infantile Neuronal Ceroid Lipofuscinosis) (CLN2 Intervention-Specific Assessment [ISA] Under the PLX-200-600 Master Protocol)
干预措施: PLX-200 (Drug)
结局指标
主要结局
To evaluate the change from baseline in 12-lead electrocardiogram in study participants 2 to 15 years old with LSDs during the treatment period.
时间窗: Week 102
To evaluate the safety and tolerability of PLX-200 in study participants 2 to 15 years old1 with LSDs2 during the treatment period.
时间窗: Until 30 days after the last administration of the study drug.
Incidence and severity of treatment-emergent adverse events (TEAEs) until 30 days after the last administration of the study drug as well as withdrawals due to the TEAEs.
To evaluate the safety and tolerability of PLX-200 in study participants 2 to 15 years old1 with LSDs2 during the treatment period.
时间窗: 30 days after the last administration of the study drug
Incidence and severity of serious adverse events (SAEs) until 30 days after the last administration of the study drug.
To evaluate the change from baseline in clinical laboratory parameters in study participants 2 to 15 years old with LSDs during the treatment period.
时间窗: Week 102
To evaluate the change from baseline in physical examination results in study participants 2 to 15 years old with LSDs during the treatment period.
时间窗: Week 102
To evaluate the change from baseline vital signs in study participants 2 to 15 years old with LSDs during the treatment period.
时间窗: Week 102
次要结局
- To evaluate the clinical activity of PLX-200 in study participants 2 to 15 years old with LSDs as measured by each respective instrument as specified in the Intervention Specific Assessment (ISA).(Week 102)
- Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (VABS-3) Score(Week 102)
- Caregiver Global Impression of Severity(Week 102)