An Open-label Study of UX003 rhGUS Enzyme Replacement Therapy in MPS 7 Patients Less Than 5 Years Old
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 5
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
研究概览
简要总结
The primary objective was to evaluate the effect of UX003 treatment in pediatric MPS VII participants less than 5 years of age on safety, tolerability, and efficacy as determined by the reduction of urinary glycosaminoglycans (uGAG) excretion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay, or genetic testing.
- •Under 5 years of age at the time of informed consent.
- •Written informed consent of Legally Authorized Representative after the nature of the study has been explained, and prior to any research-related procedures.
排除标准
- •Undergone a successful bone marrow or stem cell transplant or has evidence of any degree of detectable chimaerism with donor cells.
- •Any known hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
- •Use of any investigational product (drug or device or combination) other than UX003 within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments at any time during the study.
- •Has a condition of such severity and acuity, in the opinion of the Investigator, which may not allow safe study participation. For patients with hydrops fetalis, the ongoing interventions to manage fluid balance can be continued; if the addition of enzyme replacement therapy (ERT) is considered a fluid-overload risk, the individual should be excluded.
- •Has a concurrent disease or condition 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 affect safety. Since hydropic patients have a high rate of mortality, the risk of death prior to 1 year of age should not be considered sufficient to exclude the patient from the study for compliance.
研究组 & 干预措施
UX003
UX003 4 mg/kg every other week (QOW). Initial treatment period 48 weeks. Continuation period up to 240 weeks.
干预措施: UX003 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
时间窗: From first dose of study drug until 30 days after the last dose of study drug. Mean (SD) treatment duration was 98.11 (29.02) weeks
Adverse event (AE): any untoward medical occurrence in a participant, whether or not considered drug related. Serious AE (SAE): an AE or suspected adverse reaction that at any dose results 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. Other important medical events may also, in the opinion of the Investigator, be considered SAEs. An AE was considered a TEAE if it occurred on or after the first dose, and was not present prior to the first dose, or it was present at the first dose but increased in severity during the study. Events recorded as either possibly, probably, or definitely related to treatment were categorized as related. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.03.
Percent Change From Baseline in uGAG Excretion (LC-MS/MS-DS) at Week 48
时间窗: Baseline (Week 0), Week 48
Liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate (LS-MS/MS-DS) method. For the participant previously treated with UX003 under an eIND, percent change from initial baseline was used.
次要结局
- Change From Baseline Over Time in Standing Height(Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132)
- Change From Baseline Over Time in Head Circumference Z-Score(Baseline, Weeks 12, 24, 36, 48)
- Change From Baseline Over Time in Standing Height Z-Score(Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132)
- Change From Baseline Over Time in Head Circumference(Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132)
- Change From Baseline Over Time in Liver Measurement(Baseline, Weeks 12, 24, 48, 96, 144)
- Change From Baseline Over Time in Weight(Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132)
- Change From Baseline Over Time in Spleen Measurement(Baseline, Weeks 12, 24, 48, 96, 144)
- Post-UX003 Growth Velocity (cm/yr) for Participants With Both Historical Pre-UX003 (Within 2 Years) and Post-UX003 Data(Pre-treatment (based on standing height within 2 years prior to treatment), Post-treatment (based on all standing height data during the study period up to 240 weeks))
- Change From Pre-Treatment (Within 2 Years) to Post-Treatment Growth Velocity Z-Score(Pre-treatment (based on standing height within 2 years prior to treatment), Post-treatment (based on all standing height data during the study period up to Week 48))