A Pilot Study of NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- the longitudinal change in absolute lymphocyte count over 6 months following study drug administration
研究概览
简要总结
Background:
Progressive multifocal leukoencephalopathy (PML) is a brain infection. It is caused by a virus. PML can happen in people with a weakened immune system. PML is associated with cognitive and visual impairment as well as motor and speech disturbances. There is no treatment for PML. Researchers want to see if a new drug can help.
Objective:
To see if the drug NT-I7 can help increase lymphocyte numbers, which may help control PML infection.
Eligibility:
Adults ages 18 and older with PML who are enrolled in Protocol #13-N-0017.
Design:
Participants will be screened under Protocol #13-N-0017.
Participants will have a 7-day inpatient stay, outpatient visits, and follow-up phone calls.
Participants will have a medical history and physical exam. They will give urine samples. Blood will be drawn from an arm vein or through an intravenous (IV) catheter.
Participants will get up to 3 doses of NT-I7. It will be given by injection into the muscle.
Participants will have lumbar punctures ( spinal taps ). A thin needle will be inserted into the spinal canal in the lower back. Cerebrospinal fluid will be removed. X-ray may be used to guide the procedure.
Participants will have magnetic resonance imaging (MRI) of the brain. The MRI scanner is a metal cylinder surrounded by a magnetic field. During MRIs, participants will lie on a table that slides in and out of the scanner. Soft padding or a coil will be placed around their head. They will get gadolinium, a contrast agent, through an IV catheter.
Participation will last for 12 to 19 months.
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详细描述
Study Description:
This protocol will test whether NT-I7 is a viable strategy for promoting immune reconstitution in lymphopenic patients with PML. Twelve evaluable adults with PML and lymphopenia (CD4 or CD8 T cell count of <=200 cells/dL), without a history of autoimmune disease affecting vital organs, will complete this pilot study. Patients will be observed as inpatient for the first 7 days following any experimental drug dosing. To follow, patients will return to NIH for a second 7-day inpatient stay by Day 21, and then for scheduled outpatient visits at NIH at month 2, 3, 6, 9 and 12 following any drug dosing. Follow up phone calls will be conducted at month 4, 5, 7 and 8. Patients may be eligible for a second dose of NT-I7 at higher dose if target ALC (1000/microliter) not reached, or at same dose if initial response is adequate but not sustained, for a maximum of 3 doses. The primary outcome measure is change in absolute lymphocyte counts (ALC). Secondary outcomes include safety and tolerability. Exploratory clinical, radiological, and laboratory measures will be obtained to investigate mechanism of action of NT-I7 and for biomarker development.
Objectives:
Primary Objective: To determine the kinetics and magnitude of effect of NT-I7 on absolute lymphocyte counts in patients with PML and underlying lymphopenia from various causes, in order to inform appropriate design of a future study.
Secondary Objectives: (1) To assess safety and tolerability of NT-I7. (2) To determine kinetics and magnitude of effect of NT-I7 on lymphocyte subsets. (3) To investigate effect of NT-I7 on PML disease course. (4) To investigate mechanism of action of NT-I7.
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
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
NT-I7
480 microgram/kg IM (initial dose)
干预措施: NT-I7 (Drug)
结局指标
主要结局
the longitudinal change in absolute lymphocyte count over 6 months following study drug administration
时间窗: over 6months following study drug administration
determine the kinetics and magnitude of effect of NT-I7 on absolute lymphocyte counts (ALC) in patients with PML and underlying lymphopenia from various causes, in order to inform appropriate design of a future study
次要结局
- Change in lymphocyte subsets, including CD4, CD8, and CD19 positive cells(at each study timepoint)
- Disease course(at each study timepoint)
- Safety(at each study timepoint)