HIV Cardiac Risk Reduction and CD24Fc (CALIBER)

本研究是一项II期、随机、安慰剂对照、双盲临床试验，旨在评估CD24 Fc在HIV患者中的安全性和耐受性，以及CD24 Fc对HIV患者低密度脂蛋白（LDL）变化的影响。我们还将评价CD24 Fc对总胆固醇和甘油三酯、免疫活化标志物（T细胞活化、sCD14和炎性细胞因子）、HIV储库大小、HbA1c和瘦素以及肝脂肪变性等炎性标志物的影响。 我们假设，在接受ART的HIV患者中，CD24 Fc治疗是安全和可耐受的，并导致LDL显著降低。此外，我们假设CD24 Fc将降低ART病毒抑制的慢性HIV患者的胆固醇、瘦素、HbA1c、肝脂肪变性和纤维化以及炎症标志物。 在这项2期研究中，64名接受ART治疗的病毒抑制的HIV患者将以1：1的方式随机分组，在4周的治疗时间窗内每2周接受一次静脉输注240 mg CD24 Fc与安慰剂，随后是24周的随访期。 在24周随访期间，将对患者的安全性和不良事件以及脂质代谢和炎症标志物的变化进行随访。这项调查将在马里兰州大学和国立卫生研究院进行。 作为马里兰州大学研究的一部分，美国国立卫生研究院临床中心正在完成的研究是评估CD 24 Fc对主动脉血管炎症的影响，通过PET/CT测量动脉FDG的标准化摄取值。将选择12名LDL> 125（高水平的低密度脂蛋白（LDL），也称为坏胆固醇）的受试者进行可选的FDG PET/CT扫描。将在治疗前后评估血管炎症的变化，如通过FDG-PET/CT的主动脉FDG摄取所证明的。FDG的动脉摄取通过标准化摄取值（SUV）最大值除以静脉SUV平均值来测量，从而产生目标与背景比（TBR）。 该扫描完成两次，一次在开始研究药物之前，另一次在完成研究药物后24周。FDG PET/CT扫描将有助于确定服用研究药物或安慰剂后血管中的炎症水平是否有任何变化。 本研究将在取消COVID对患者招募的限制后开始入组。

This study is a phase 2, randomized, placebo-control, double-blinded clinical trial to assess the safety and tolerability of CD24Fc among patients with HIV, and the effect of CD24Fc on change in low-density lipoprotein (LDL) among patients with HIV. We will also evaluate the effect of CD24Fc on total cholesterol and triglycerides, markers of immune activation (T cell activation, sCD14, and inflammatory cytokines), size of HIV reservoirs, HbA1c and leptin, and hepatic steatosis, among other inflammatory markers. We hypothesize that therapy with CD24Fc will be safe and tolerable in HIV patients on ART, and result in significant decreases in LDL. In addition, we hypothesize that CD24Fc will reduce cholesterol, leptin, HbA1c, hepatic steatosis and fibrosis, and markers of inflammation in patients with chronic HIV who are virally suppressed on ART. In this phase 2 study, a cohort of 64 HIV patients virally suppressed on ART will be randomized in a 1:1 fashion to receive an intravenous infusion of 240mg of CD24Fc vs. placebo administered every 2 weeks during a 4-week treatment window, followed by a 24- week follow-up period. Patients will be followed for safety and adverse events as well as changes in lipid metabolism and inflammatory markers during a 24-week follow-up period. This investigation will take place at the University of Maryland and National Institutes of Health. The research being completed at the National Institutes of Health Clinical Center as part of the University of Maryland study is to assess the effect of CD24Fc on aortic vascular inflammation as measured by standardized uptake value of arterial FDG by PET/CT. Twelve subjects with an LDL>125 (a high level of low-density lipoproteins (LDL), also known as bad cholesterol) will be selected to have an optional FDG PET/CT scan. Change in vascular inflammation as evidenced by aortic FDG uptake by FDG-PET/CT will be assessed before and after therapy. The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUV mean yielding a target to background ratio (TBR). This scan is completed twice, once before starting the study drug, and again 24 weeks after completing the study drug. The FDG PET/CT scans will help to determine if there are any changes to the levels of inflammation in the blood vessels after taking the study drug, or placebo. This study will start enrolling when COVID restrictions on patient accrual are removed.