2024-511192-15-00招募中2 期
Optimizing reversal of HIV latency with combination therapy (pyrimethamine, lenalidomide, panobinostat)
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)3 个研究点 分布在 1 个国家目标入组 49 人开始时间: 2024年5月7日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 49
- 试验地点
- 3
- 主要终点
- The fold change in cell-associated HIV-RNA at time points 6 and 24 hours as compared to baseline (time point 0 hour)
研究概览
简要总结
To longitudinally assess dual latency-reversing agent combination treatments on HIV reservoir reactivation and tolerability in people with HIV.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Documented HIV-1 infection by 4th generation ELISA, Western Blot or PCR. • ≥ 18 years old. • World Health Organization (WHO) performance status 0 or
- •Current plasma HIV RNA <50 copies/ml measured on the last 2 occasions, with measurements being at least 3 months apart. • Uninterrupted prescribed ART for a minimum of two consecutive years. • Considered >95% adherent to ART by treating physician. • Current blood CD4+T-cell count of ≥200 cells/mm3 • No clinical signs of cellular immunodeficiency or AIDS. • Pre-ART plasma HIV RNA ≥1000 copies/mL. • Confirmed HIV subtype B. People with a high likelihood of subtype B can participate if they live in a HIV subtype B endemic region with HIV acquired there and in whom no HIV sequencing is available or can be done on stored samples. • People should be considered capable mentally and somatically by their treating physician to understand the informed consent procedure and undergo the study treatment.
排除标准
- •A potential subject who meets any of the following criteria will be excluded from participation in this study: • Previous exposure to any of the studied LRAs in the last year • Acute or chronic co-infection with hepatitis B and/or C by the presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA in blood. • Co-medication with clinically significant interactions with LRA (see chapter 15.h for list) • Comorbidities affected by LRA compounds, such as but not limited to: known Glucose-6-phospate-dehydrogenase (G6PD) deficiency with anaemia, untreated haemolysis of any cause or hereditary thrombophilia not currently treated by anticoagulation. • Prolonged Qtc time >480ms at screening, as measured by electrocardiogram (ECG). • Patients of childbearing potential unless double contraceptive measures are taken. Non-childbearing is defined by one of the following criteria: amenorrhoea for ≥ 1 year, premature ovarian failure, assigned male at birth, or having undergone previous bilateral salpingo-oophorectomy, or hysterectomy • Sexual active patients unwilling to abstain from sex unless willing to use condom protection during and until 1 week after administration of study medication. • Active malignancy during the past year with the exception of basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi’s sarcoma treated with ARTalone or other indolent malignancies. • Registered allergies for any of the investigational medical products • Any lab abnormalities at screening as listed below: • Moderate kidney impairment, def ined as eGFR <50 mL/min. In PLWH on dolutegravir- or bictegravir-based ART regimens, cystatin C-based eGFR can be used, as creatinine-based eGFR is underestimat ed due to drug interf erence with tubular creatinine excretion which leads to eGFR underestimation. • Moderate hepatic impairment, defined as bilirubin > 3 x upper limit of normal (ULN) or ALT > 3x ULN • Inadequate blood counts, defined as: Haemoglobin <6.5 mmol/L (males) or <6.0 mmol/L (females), absolute neutrophil count <1000 cells/mm3, thrombocytes <100 x109/L, international standardized ratio >1.6, activated partial thromboplastin time >40 seconds, serum sodium <130 mmol/L, serum potassium <3.0 mmol/L, serum phosphate <0.5 mmol/L, serum calcium <1.9 mmol/L, serum magnesium <0.5 mmol/L.
结局指标
主要结局
The fold change in cell-associated HIV-RNA at time points 6 and 24 hours as compared to baseline (time point 0 hour)
The fold change in cell-associated HIV-RNA at time points 6 and 24 hours as compared to baseline (time point 0 hour)
The number and severity of clinical and biochemical adverse events considered by the investigator to be related to any of the investigational drugs.
The number and severity of clinical and biochemical adverse events considered by the investigator to be related to any of the investigational drugs.
次要结局
- 1. The fold change in cell-associated HIV-RNA on LRA monotherapy components compared to combination LRA treatments.
- 2. The change in the HIV reservoir size and genetic composition from baseline to the end of the study.
- 3. The level of immune activation, and phenotype and functionality of the cellular immunity as compared from baseline to end of treatment.
- 4. The plasma concentrations of the investigational drugs during treatment.
- 5. Correlations of ex vivo and in-vivo cell associated HIV-RNA responses to the investigational drugs.
- 6. The association between clinical variables and the primary endpoints.
- 7. The number and frequency of measurable (above limit of detection or above limit of quantitation) plasma HIV-RNA during treatment.
- 8. Number of upward and downward counterfactuals
研究者
Casper Rokx
Scientific
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
研究点 (3)
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