An Open-Label Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Amgen
- 入组人数
- 15
- 试验地点
- 19
- 主要终点
- Maximum Observed Concentration (Cmax) of Inebilizumab
研究概览
简要总结
A Phase 2, open-label, multicenter study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of inebilizumab in eligible pediatric participants 2 to < 18 years of age with recently active neuromyelitis optica spectrum disorder (NMOSD) who are seropositive for autoantibodies against aquaporin-4 (AQP4-immunoglobulin [Ig]G).
详细描述
Approximately 15 participants to be enrolled and receive Inebilizumab administered intravenously over 28 weeks. The maximum trial duration per participant is approximately 80 weeks, including up to 4 week screening period, 9 visits during a 28 week open-label treatment period, and approximately 4 visits during a 52 week follow-up period. Safety evaluations will be performed regularly throughout the course of the study.
Acquired from Horizon in 2023.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants, minimum body weight of 15 kg, age 2 to < 18 years at the time of screening.
- •Positive serum anti-AQP4-IgG result at screening and diagnosed with NMOSD according to the criteria of Wingerchuk et al,
- •Documented history of one or more NMOSD acute relapses within the last year, or 2 or more NMOSD acute relapses within 2 years prior to screening.
排除标准
- •Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the Investigational Product or interpretation of participant safety or study results.
- •Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is the longer, prior to Day
- •Evidence of significant hepatic, renal, or metabolic dysfunction or significant hematological abnormality (one repeat test may be conducted to confirm results within the same screening period).
- •B-cell counts < one-half of the lower limit of normal (LLN) for age according to the central laboratory.
- •Receipt of the following at any time prior to Day 1:
- •Alemtuzumab
- •Total lymphoid irradiation
- •Bone marrow transplant
- •T-cell vaccination therapy
- •Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior to screening unless B-cell counts have returned to ≥ one-half the LLN.
- •Receipt of intravenous immunoglobulin (IVIG) within one month prior to Day
- •Receipt of any of the following within 2 months prior to Day 1:
- •Cyclosporine
- •Methotrexate
- •Mitoxantrone
- •Cyclophosphamide
- •Tocilizumab
- •Satralizumab
- •Receipt of natalizumab (Tysabri®) within 6 months prior to Day
- •Severe drug allergic history or anaphylaxis to 2 or more food products or medicine (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid).
- •Diagnosed with a concurrent autoimmune disease that is uncontrolled (unless approved by the medical monitor).
- •Recent receipt of live/attenuated vaccine or blood transfusion.
- •Receipt of any of the following:
- •Any live or attenuated vaccine within 4 weeks prior to Day 1 (administration of killed vaccines and nucleoside-modified mRNA-based vaccines is acceptable; the Sponsor recommends that Investigators ensure all participants are up to date on required vaccinations prior to study entry).
- •Bacillus Calmette Guérin vaccine within one year of screening.
- •Blood transfusion within 4 weeks prior to screening or during screening.
- •Clinically significant serious active or chronic viral, bacterial, or fungal infection that requires treatment with anti-infectives, hospitalization, or, in the Investigator's opinion, represents an additional risk to the participant, within 2 months prior to Day
- •Known history of congenital or acquired immunodeficiency (e.g., due to human immunodeficiency virus [HIV] infection, splenectomy, immunosuppression-related or idiopathic T-cell deficiencies) that predisposes the participant to infection.
- •Positive test for chronic hepatitis B infection at screening, defined as either:
- •a. Positive hepatitis B surface antigen (HBsAg), or b. Positive hepatitis B core (HBc) antibody (anti-HBc) plus negative hepatitis B surface (HBs) antibody (anti-HBs).
- •Positive test for hepatitis C virus antibody.
- •Negative test for varicella zoster virus (VZV)-IgG.
- •History of cancer, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy > 3 months prior to Day
- •History of active or latent tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening, unless treatment for TB was completed per local guidelines. Participants with latent TB or a positive QuantiFERON®-TB Gold test who are actively on anti-TB treatment can enroll if they have completed at least one month of anti-TB treatment and intend to complete the full course of anti-TB treatment. Participants with an indeterminate QuantiFERON®-TB Gold test result can enroll if a repeat QuantiFERON®-TB Gold test is negative or a tuberculin skin test is negative.
- •For participants who may undergo MRI scans:
- •Unable to undergo an MRI scan (e.g., hypersensitivity to Gd-containing MRI contrast agents, implanted pacemakers, defibrillators, or other metallic objects on or inside the body that limit performing MRI scans), or
- •Unable to tolerate or comply with the MRI procedure.
研究组 & 干预措施
Inebilizumab
Infusion of Inebilizumab
干预措施: Inebilizumab (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Inebilizumab
时间窗: Day 1 to Week 28
Area Under the Concentration Versus Time Curve of Inebilizumab from Time 0 to 14 Days Post-dose (AUC0-14d)
时间窗: Day 1 to pre-dose on Day 15
Area Under the Concentration Versus Time Curve of Inebilizumab from Time 0 Extrapolated to Infinity (AUC0-Inf)
时间窗: Day 1 to Week 80
Systemic Clearance (CL) of Inebilizumab
时间窗: Day 1 to Week 80
Terminal Elimination Half-life (t½) of Inebilizumab
时间窗: Day 1 to Week 80
Volume of Distribution at Steady State (VSS) of Inebilizumab
时间窗: Day 1 to Week 80
Change from Baseline in Peripheral Cluster of Differentiation (CD)20-positive B-cell Counts
时间窗: Week 1, Week 2, Week 28, Week 80
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
时间窗: Day 1 to Week 80
Change from Baseline in Serum Chemistry
时间窗: Week 1, Week 2, Week 28, Week 80
Change from Baseline in Hematology
时间窗: Week 1, Week 2, Week 28, Week 80
Change from Baseline in Serum Immunoglobulins
时间窗: Week 1, Week 2, Week 28, Week 80
Change from Baseline in Systolic Blood Pressure
时间窗: Week 1, Week 2, Week 28, Week 80
Change from Baseline in Diastolic Blood Pressure
时间窗: Week 1, Week 2, Week 28, Week 80
Change from Baseline in Pulse Rate
时间窗: Week 1, Week 2, Week 28, Week 80
Change from Baseline in Respiratory Rate
时间窗: Week 1, Week 2, Week 28, Week 80
Change from Baseline in Body Temperature
时间窗: Week 1, Week 2, Week 28, Week 80
次要结局
- Change From Baseline in Expanded Disability Status Scale(Day 1 to Week 80)
- Anti-drug antibody (ADA) rate(Day 1 to Week 80)
- Disease Activity: Time to First Relapse(Day 1 to Week 80)
- Disease Activity: Proportion of Relapse-free Participants(Day 1 to Week 80)
- Disease Activity: Annualized Relapse Rate(Day 1 to Week 80)
- Health-Related Quality of Life (HRQoL) change from baseline in Euro Quality of Life-5 Dimension Youth score(Day 1 to Week 80)
- HRQoL change from baseline in Pediatric Quality of Life Inventory(Day 1 to Week 80)
- Visual Acuity change from baseline(Day 1 to Week 80)