An Open-Label Extension to Investigate the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Patients With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 99
- 试验地点
- 29
- 主要终点
- Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
研究概览
简要总结
This is a multiregional open-label extension (OLE) to assess the safety, tolerability, and efficacy of long-term treatment with tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant intravenous (IV) enzyme replacement therapy (ERT) for Hunter syndrome (MPS II). Participants who complete at least through the Week 49 visit in Study DNLI-E-0002 and do not discontinue study intervention early and participants who complete Study DNLI-E-0007 will be enrolled in this OLE. All participants will receive DNL310 for up to 5 years from the time of entry in this OLE. Participants, site staff, and the Sponsor will remain blinded to the original treatment assignment for participants entering this OLE from Study DNLI-E-0007.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early
- •For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants
排除标准
- •Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
研究组 & 干预措施
Cohort A7
Participants with nMPS II, aged ≥2 to <6 years
干预措施: tividenofusp alfa (Drug)
Cohort B7
Participants with nnMPS II, aged ≥6 to <17 years
干预措施: tividenofusp alfa (Drug)
Cohort A2
Participants with nMPS II, aged ≥5 to ≤10 years
干预措施: tividenofusp alfa (Drug)
Cohort B2
Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years
干预措施: tividenofusp alfa (Drug)
Cohort C2
Participants with nMPS II, aged <4 years
干预措施: tividenofusp alfa (Drug)
Cohort D2
Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT
干预措施: tividenofusp alfa (Drug)
Cohort E2
Participants with nMPS II, aged ≥6 years; participants with nnMPS II, aged <6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001
干预措施: tividenofusp alfa (Drug)
结局指标
主要结局
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
时间窗: 5 years
Incidence and intensity of treatment-emergent adverse events (TEAEs)
时间窗: 5 years
Incidence and intensity of infusion-related reactions (IRRs)
时间窗: 5 years
The intensity of IRRs will be assessed following each infusion of DNL310 using the categories of Mild, Moderate and Severe. IRRs will be summarized overall as well as stratified by intensity.
次要结局
- Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score(5 years)
- Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration(5 years)
- Liver volume within the normal range (normal vs abnormal) as measured by MRI(5 years)
- Change from baseline in the Vineland-3 Adaptive Behavior Scale(5 years)
- Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)(5 years)
- Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations(5 years)
- Spleen volume within the normal range (normal vs abnormal) as measured by MRI(5 years)
- Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II(5 years)