A Phase 1 Study of Repeat PET/CT Imaging in People With CAPS and Anakinra-Induced Amyloidosis Using Amyloid-Reactive Peptide 124I-AT-01 (124I-p5+14, Iodine-124I-Evuzamitide) to Measure Changes in Organ-Specific Amyloid Load
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in organ-specific 124I AT-01 uptake from baseline PET/CT imaging to the follow up PET/CT imaging every 6 months for 2 years.
研究概览
简要总结
Background:
Anakinra is a drug used to treat people with certain diseases that affect their immune systems. Sometimes anakinra can cause proteins under the skin to clump together. These clumps are called amyloidosis; they can spread to other organs. The only way to diagnose amyloidosis is to remove a piece of tissue (biopsy). Researchers want to find a way to locate amyloidosis in internal organs using positron emission tomography (PET)/computed tomography (CT).
Objective:
To test a new tracer used during PET/CT scans in people with amyloidosis. A tracer is a radioactive dye injected into the body.
Eligibility:
Adults aged 18 years or older with amyloidosis from anakinra injections. They must be enrolled in NIH protocol 17-I-0016.
Design:
Participants will come to the clinic once every 6 months for 2 years. Each visit will be 1 day.
They will have a PET/CT scan with the new tracer at each visit: The tracer will be given through a tube attached to a needle inserted into a vein.
The PET/CT scanner is a machine shaped like a doughnut. Participants will lie still on a padded table. The table will move in and out of the machine. The scan takes about 1 hour.
Radiation from the tracer will remain in the body for 24 hours after each scan. Participants will need to follow rules to avoid exposing pets and other people.
Participants will collect a 24-hour urine sample before each visit. They will also have blood tests and a physical exam at each visit.
Participants will receive a follow-up phone call about 1 week after each visit.
详细描述
Study Description:
This is a phase 1 study to evaluate the feasibility of an investigational positron emission tomography (PET)/computed tomography (CT) radiotracer, 124I-AT-01, to screen for anakinra-induced amyloidosis in people with the cryopyrin-associated autoinflammatory syndromes (CAPS) (Muckle-Wells syndrome [MWS] or neonatal onset multisystem inflammatory disease [NOMID]), and to follow resolution of amyloidosis. This radiotracer binds to amyloid, so a PET/CT scan can show the presence and relative magnitude of amyloid.
Participants aged 18 years and older who developed local skin or systemic amyloidosis as a result of anakinra treatment will be recruited. They will have a PET/CT scan with radiotracer 124I-AT-01 about once every 6 months for 2 years. Blood and urine will be collected for clinical safety analyses, but no specimen will be collected for research or storage purposes.
The 124I-AT-01 PET/CT imaging is expected to be able to detect anakinra-induced amyloid in the skin and other organs (such as kidney, liver, and spleen). The percent change in quantitative uptake of 124I-AT-01 from baseline to each subsequent scan is expected to correlate with changes in clinical features related to load of amyloid in the body.
Primary Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 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
- •INCLUSION CRITERIA:
- •An individual must meet all the following criteria to be eligible for this study:
- •Aged 18 years and older.
- •Currently enrolled on NIH protocol 17-I-0016 with a documented diagnosis of MWS or NOMID.
- •Agree to allow data collected in this study to be shared with and stored on NIH protocol 17-I-0016 for that study s research analyses.
- •Developed skin thickening at the site of anakinra injection.
- •Participants who can become pregnant or who can impregnate their partner must agree to use 2 highly effective methods of contraception, at least 1 of which must be a barrier method, when engaging in sexual activities that can result in pregnancy, beginning 28 days prior to baseline until 90 days after the last PET/CT scan. Acceptable methods of contraception include the following:
- •Barrier methods:
- •External or internal condom with spermicide.
- •Diaphragm or cervical cap with a spermicide.
- •Non-barrier methods:
- •Hormonal contraception.
- •Intrauterine device.
- •Hysterectomy, oophorectomy, or tubal ligation in women
- •Vasectomy in men
排除标准
- •Known hypersensitivity to 124I-AT-01, AT-01, or any of their excipients.
- •Known hypersensitivity to KI.
- •Pregnant or breastfeeding.
- •Currently receiving dialysis.
- •Currently taking heparin or heparin derivatives (eg, low molecular weight heparins) or other blood thinners for anticoagulation.
- •Any condition that, in the opinion of the study team, contraindicates participation in this study.
研究组 & 干预措施
Interventional
Participants aged 18 years and older with anakinra-type amyloidosis (n=10) will be recruited from NIH protocol 17-I-0016. Upon confirmation of eligibility, they will undergo a PET/CT scan with the investigational radiotracer 124I-AT-01, which selectively binds to amyloid fibers. Blood and urine will also be collected for clinical and research analyses, including measurement of IL-1RA and other biomarkers. These scans and sample collections will be repeated about once every 6 months for 2 years.
干预措施: 124I AT-01 (Drug)
结局指标
主要结局
Change in organ-specific 124I AT-01 uptake from baseline PET/CT imaging to the follow up PET/CT imaging every 6 months for 2 years.
时间窗: 2 years
The gold standard for detecting amyloid deposits is tissue biopsy. With this compound, we expect to detect evidence of tissue deposits in the tissue at a much earlier stage and in a non invasive manner. By lowering the exposure to anakinra in participants with anakinra-associated systemic amyloidosis, the burden of amyloidosis is expected to reduce over time.
Frequency of CAPS disease flares after exposure to 124I AT 01.
时间窗: Through end of study.
This compound has not been used in patients with CAPS. We will monitor the participants to detect possible inflammatory disease flare following the exposure.
次要结局
未报告次要终点