A Phase 1, Open-Label, Single and Multiple Ascending Dose Study of ABC008 in Adult Patients with Inclusion Body Myositis (IBM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Abcuro, Inc.
- 入组人数
- 19
- 试验地点
- 4
- 主要终点
- Assessment of Safety and Tolerability
研究概览
简要总结
An open-label, ascending dose study for adult patients with Inclusion Body Myositis (IBM).
详细描述
Participants who successfully complete the SAD EOT visit, and have no emerging safety issues, will be eligible to enroll in Part 2 (MAD). Eligible participants for the MAD part will have inclusion and exclusion criteria (same as those for Part 1) reviewed prior to dosing on MAD Day 1.
Participants who successfully complete the MAD EOT visit, and have no emerging safety issues, will be eligible to enrol in Part 3, MAD Extension.
After the final MAD visit (W48), participants will have the option to continue on to Part 3 MAD Extension.
For Part 3 (MAD Extension), participant dosing will be at 8-week intervals starting at Day 1. Duration of dosing in Part 3 will be up to approximately 80 weeks (18 months), or until a new long-term extension study has been initiated. The SMC will review all participant safety data approximately every 6 months while the Part 3 dosing continues.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of either clinico-pathologically defined IBM, clinically defined IBM, or probable IBM according to the European Neuromuscular Center (ENMC) IBM 2011
- •Able to arise from a chair (with or without armrests) without support from another person or device
- •Able to ambulate at least 20 feet / 6 meters with or without assistive device
排除标准
- •Taking > 7.5 mg prednisolone (or equivalent) or on intravenous immunoglobulin (IVIg) or other immunosuppressants within the last 3 months. Topical, nasal, and ocular corticosteroids are allowed unless they are being widely applied or the severity of the underlying condition makes them unsuitable in the Investigator's opinion. Local steroid injections are allowed
研究组 & 干预措施
Cohort D3
Single Dose 2.0 mg / kg ABC008
干预措施: ABC008 (Drug)
Cohort D1
Single Dose 0.1 mg / kg ABC008
干预措施: ABC008 (Drug)
Cohort D2
Single Dose 0.5 mg / kg ABC008
干预措施: ABC008 (Drug)
Cohort D4
Single Dose 5.0 mg / kg ABC008
干预措施: ABC008 (Drug)
Cohort D5
X.X mg / kg ABC008
干预措施: ABC008 (Drug)
Cohort 6
Single 2.0 mg / kg ABC008
干预措施: ABC008 (Drug)
MAD Phase Cohort 1
Multiple Dose 0.1 mg / kg ABC008 every 8 weeks
干预措施: ABC008 (Drug)
MAD Phase Cohort 2
Multiple Dose 0.5 mg / kg ABC008 every 8 weeks
干预措施: ABC008 (Drug)
MAD Phase Cohort 3
Multiple Dose 2.0 mg / kg ABC008 every 8 weeks
干预措施: ABC008 (Drug)
结局指标
主要结局
Assessment of Safety and Tolerability
时间窗: Through Study Completion an average of 28 weeks for SAD (Single Ascending Dose) phase and 52 weeks for MAD (Multiple Ascending Dose) phase]
Characterize the safety and tolerability profile of single (SAD) and multiple (MAD) escalating dose levels of ABC008 in IBM when administered subcutaneously (SC) as measured by the number and severity of treatment emergent adverse events, serious adverse events, and adverse events of special interest, number of dose limiting toxicities.
次要结局
- Assessment of peak serum concentration (Cmax)(Day 1 and throughout the 24 weeks of follow up)
- Assessment of apparent volume of distribution (Vz/F)(Day 1 and throughout the 24 weeks of follow up)
- Assessment of global distribution of [ 89Zr]Zr-Df-crefmirlimab uptake in skeletal muscle([Through Study Completion, avg. 48 weeks)
- Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis mean (SUVmean)([Through Study Completion, avg. 48 weeks)
- Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis maximum (SUVmax)([Through Study Completion, avg. 48 weeks)
- Assessment of area under the concentration versus time curve from time zero to 24 hours post-dose (AUC0-24hr)(Day 1)
- Assessment of global distribution of [ 89Zr]Zr-Df-crefmirlimab uptake in lymphoid organs([Through Study Completion, avg. 48 weeks)
- Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis peak (SUVpeak)([Through Study Completion, avg. 48 weeks)
- Assessment of time to peak serum concentration (Tmax)(Day 1 and throughout the 24 weeks of follow up)
- Assessment of terminal half-life (t½)(Day 1)
- Assessment of apparent clearance (CL/F)(Day 1 and throughout the 24 weeks of follow up)
- Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab pre and post dosing of ABC008([Through Study Completion, avg. 48 weeks)
- Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis SUV of diseased muscle([Through Study Completion, avg. 48 weeks)
- Characterization of changes in KLRG1 expressing lymphocytes(Day 1 and throughout the 24 weeks of follow up)
- Qualitative assessment of [ 89Zr]Zr-Df-crefmirlimab([Through Study Completion, avg. 48 weeks)
- Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis SUV reference tissue([Through Study Completion, avg. 48 weeks)