A Phase I PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients With Acute Myocarditis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- To assess the feasibility of detecting affected cardiac tissue in patients with acute myocarditis
研究概览
简要总结
The proposed patient study represents the first-ever acute myocarditis patient imaging study with 64Cu-GRIP B PET. The tracer is designed to detect extracellular granzyme B as it is secreted by activated cytotoxic T lymphocytes in the cardiomyocyte inflammatory microenvironment, highlighting areas of CD8 T cell activity leading to cardiomyocyte damage. Myocarditis is characterized pathologically by myocardial infiltration of T cells and macrophages with presence of cardiomyocyte death - the proposed tracer tests for both the accumulation of CD8 T cells and their cytotoxic activity, which will hopefully significantly improve diagnostic certainty. The study population is focused on patients with acute myocarditis to assess the specificity and sensitivity of 64Cu-GRIP B to detect myocarditis. In future studies, 64Cu-GRIP B PET may also serve as a biomarker to monitor early response to immunomodulatory therapies to treat acute myocarditis.
Each year at UCSF, the investigators encounter about 20 patients with acute myocarditis. These patients often present with non-specific cardiac symptoms with some evidence of cardiac injury (abnormal electrocardiogram or elevation in cardiac biomarkers such as troponin). Rarely is the diagnosis clear and often numerous additional clinical studies are necessary to rule out other common causes of cardiac injury like myocardial infarction. Patients identified with acute myocarditis by the investigators will receive standard clinical testing as appropriate and will also be consented to participate in a PET study with 64Cu-GRIP B. Over the course of this proposal, the investigators expect to enroll 10 patients who are being evaluated for acute myocarditis determined by current standard of care diagnostic modalities. The investigators will perform this feasibility assessment in parallel to the usual clinical care.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically or cytologically confirmed myocarditis in accordance with the Dallas Criteria
- •The subject is able and willing to comply with study procedures and provide signed and dated informed consent
- •Age ≥18 years
- •Demonstrates adequate organ function as defined below:
- •Adequate bone marrow function:
- •absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL
- •Adequate hepatic function:
- •total bilirubin within normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits AST(SGOT) ≤3 X institutional upper limit of normal ALT(SGPT) ≤3 X institutional upper limit of normal
- •Adequate renal function:
- •creatinine ≤ 1.5 x within institutional upper limit of normal OR creatinine clearance GFR ≥ 60 mL/min/1.73 m2, calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2
- •Ability to understand and the willingness to sign a written informed consent document.
- •Human immunodeficiency virus (HIV)-infected individuals on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- •For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- •Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- •The effects of 64Cu-GRIP B on the developing human fetus are unknown. For this reason and because a diagnostic PET radiotracer that is used in this trial is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception for the duration of study participation and for 2 weeks after last administration of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- •Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 2 weeks after administration of study drug.
排除标准
- •Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks. Concomitant administration of LHRH analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care.
- •Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia).
- •Is currently receiving any other investigational agents.
- •Has participated in a study of an investigational product and received study treatment or used an investigational device within 6 weeks of the first dose of study drug.
- •Any other cardiac condition that may result in non-specific findings, including recent (within 6 months) Acute Coronary Syndrome or Type II NSTEMI. Participants with a recent viral infection, such as Influenza A, will also be excluded.
- •Hypersensitivity to PET radiotracers or any of its excipients.
- •Pregnant women are excluded from this study because 64Cu-GRIP B is a PET radiotracer with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to assessment of the mother with 64Cu-GRIP B, breastfeeding should be discontinued if the mother is treated with 64Cu-GRIP
研究组 & 干预措施
Cohort A: participants with acute myocarditis (5 males, 5 females)
Participants will undergo whole body PET imaging 4 hours (+/- 1 hour) following 64Cu-GRIP B injections. 64Cu-GRIP B will be administered on an outpatient basis. It will be administered intravenously prior to PET imaging.
干预措施: 64Cu-GRIP B is a radiolabeled peptide tracer, a copper-64 isotope bound to a peptide designed to target extracellular Granzyme B (Drug)
结局指标
主要结局
To assess the feasibility of detecting affected cardiac tissue in patients with acute myocarditis
时间窗: From first dose administration through the safety follow-up at Day 70
• SUVmax of at least 1.5-fold above adjacent background at 4 hours post injection
To descriptively compare the number of areas of cardiac inflammation detected on ⁶⁴Cu-GRIP B PET imaging with those observed in a separate ⁶⁴Cu-GRIP B PET study of patients with cancer
时间窗: From first dose administration through the safety follow-up at Day 70
• Compare the uptake in acute myocarditis cohort compared to the cohort from NCT05888532 that are undergoing the same PET imaging protocol but have no signs of myocarditis.
次要结局
- Association Between 64Cu-GRIP B PET Uptake and Blood-Based Immune Parameters(From first dose administration through the safety follow-up at Day 70)
- Association Between 64Cu-GRIP B PET Uptake and Circulating Immune Cell Populations(From first dose administration through the safety follow-up at Day 70)
- Association Between 64Cu-GRIP B PET Uptake and Tissue-Based Immune Parameters(From first dose administration through the safety follow-up at Day 70)
研究者
Javid Moslehi, MD
Professor in Residence, Cardiology
University of California, San Francisco