A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 65
- 试验地点
- 62
- 主要终点
- Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
研究概览
简要总结
This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II).
Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 2 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <26 years (Cohort B)
- •Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
- •Have no history of treatment with enzyme replacement therapy (ERT) OR not have received continuous ERT for 4 months prior to screening OR be on maintenance ERT and have tolerated idursulfase for a minimum of 4 months prior to screening
排除标准
- •Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay
- •Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy
- •Received any CNS-targeted MPS ERT within 6 months prior to screening
- •Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRI)
- •Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study
研究组 & 干预措施
Cohort A: Participants with nMPS II
干预措施: tividenofusp alfa (Drug)
Cohort A: Participants with nMPS II
干预措施: idursulfase (Drug)
Cohort B: Participants with nnMPS II
干预措施: idursulfase (Drug)
Open-label Treatment Phase
Participants who meet pre-specified criteria may receive DNL310 or idursulfase
干预措施: tividenofusp alfa (Drug)
Open-label Treatment Phase
Participants who meet pre-specified criteria may receive DNL310 or idursulfase
干预措施: idursulfase (Drug)
Cohort B: Participants with nnMPS II
干预措施: tividenofusp alfa (Drug)
结局指标
主要结局
Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
时间窗: 96 weeks
Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
时间窗: 24 weeks
Ratio to baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
时间窗: 24 weeks
次要结局
- Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)(96 weeks)
- Change from baseline in serum neurofilament light chain (NfL) (Cohort A only)(96 weeks)
- Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (Cohorts A and B)(up to 48 weeks)
- Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)(48 weeks)
- Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)(48 weeks)
- Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC; Cohort A only)(96 weeks)
- Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)(48 weeks)
- Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)(48 weeks)
- Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC) score (Cohort A only)(96 weeks)
- Ratio to baseline in serum neurofilament light chain (NfL) (Cohort A only)(96 weeks)
- Ratio to baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (normalized to creatinine) (Cohorts A and B)(up to 48 weeks)