A Randomized, Placebo-Controlled, Blind-Start, Single-Crossover Phase 3 Study to Assess the Efficacy and Safety of UX003 rhGUS Enzyme Replacement Therapy in Patients With MPS 7
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 4
- 主要终点
- European Union (EU) and Rest of World: Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate (DS) at UX003 Treatment Week 24
研究概览
简要总结
The Phase 3 study will use a novel randomized, intra-subject placebo-controlled, single crossover design, referred to as Blind Start, to evaluate the safety and efficacy of UX003. The Blind Start is a novel design whereby participants will be randomized to 1 of 4 groups, each representing a different treatment sequence, and will cross over to UX003 at different pre-defined time points in a blinded manner. All groups will receive a minimum of 24 weeks treatment with 4 mg/kg UX003 every other week (QOW).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 35 Years（Child, Adult）
- 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.
- •Elevated urinary glycosaminoglycan (uGAG) excretion at a minimum of 3-fold over the mean normal for age (at Screening).
- •Apparent clinical signs of lysosomal storage disease as judged by the Investigator, including at least one of the following: enlarged liver and spleen, joint limitations, airway obstruction or pulmonary problems, limitation of mobility while still ambulatory.
- •Aged 5 - 35 years, inclusive.
- •Willing and able to provide written informed consent, or in the case of subjects under the age of 18 (or 16 years, depending on the region), provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
- •Sexually active subjects must be willing to use acceptable highly effective methods of contraception while participating in the study and for 30 days following the last dose.
- •Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not experienced menarche, or have had tubal ligation at least one year prior to Screening, or who have had total hysterectomy.
- •Naïve to treatment with UX003.
排除标准
- •Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells.
- •Major surgery within 3 months prior to study entry or planned major surgery during the study that may not allow safe participation in the study.
- •Presence or history of any hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
- •Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
- •Use of any investigational product (drug or device or combination) within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
- •Presence of a condition of such severity and acuity that, in the opinion of the Investigator, warrants immediate surgical intervention or other treatment or may not allow safe participation in the study.
- •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 introduce additional safety concerns.
研究组 & 干预措施
Group A: 4 mg/kg UX003
4 mg/kg UX003 QOW through Week 46
干预措施: UX003 (Drug)
Group B: 8 Weeks Placebo then 4 mg/kg UX003
Placebo QOW for the first 8 weeks followed by 4 mg/kg UX003 QOW through Week 46
干预措施: UX003 (Drug)
Group B: 8 Weeks Placebo then 4 mg/kg UX003
Placebo QOW for the first 8 weeks followed by 4 mg/kg UX003 QOW through Week 46
干预措施: Placebo (Other)
Group C: 16 Weeks Placebo then 4 mg/kg UX003
Placebo QOW for the first 16 weeks followed by 4 mg/kg UX003 QOW through Week 46
干预措施: UX003 (Drug)
Group C: 16 Weeks Placebo then 4 mg/kg UX003
Placebo QOW for the first 16 weeks followed by 4 mg/kg UX003 QOW through Week 46
干预措施: Placebo (Other)
Group D: 24 Weeks Placebo then 4 mg/kg UX003
Placebo QOW for the first 24 weeks followed by 4 mg/kg UX003 QOW through Week 46
干预措施: UX003 (Drug)
Group D: 24 Weeks Placebo then 4 mg/kg UX003
Placebo QOW for the first 24 weeks followed by 4 mg/kg UX003 QOW through Week 46
干预措施: Placebo (Other)
结局指标
主要结局
European Union (EU) and Rest of World: Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate (DS) at UX003 Treatment Week 24
时间窗: Baseline (defined as the average of all assessments prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment
Baseline was defined as the average of all assessments prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect was subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Percent change from baseline in uGAG DS was analyzed by generalized estimating equation (GEE) modeling based on observed data. The GEE model included included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within subjects was assumed to be exchangeable. In the United States (US), this was considered a secondary outcome measure. Per guidance from the Food and Drug Administration (FDA), no primary efficacy variable was declared in the US. Efficacy was to be based on the totality of the clinical data on a per participant basis.
次要结局
- Multi-Domain Responder Index (MDRI) Score at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in 6-Minute Walk Test (6MWT) at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in Pulmonary Function Testing: Percentage of Predicted Forced Vital Capacity (FVC%Pred) at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in Pulmonary Function Testing: Maximum Ventilatory Ventilation (MVV) at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in Shoulder Flexion and Extension Maximum Range of Motion at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in Uncorrected Visual Acuity at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) Scores at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Percentage of Individual Clinical Response (ICR) Responders at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)
- Change From Baseline in Impactful Clinical Problem Total Score at UX003 Treatment Week 24(Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment)