2026-525211-14-00招募中2 期
Curing HIV: proof of concept randomized clinical trial with Pyrimethamine, Lenalidomide, TOpiramate (PLUTO)
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)6 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2026年5月4日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Phase I : Fold change in cell-associated HIV-RNA at time points 6 (T=6) and 24 hours (T=24) after LRA treatment compared to baseline (T=0) before treatment. Phase II: Log transformed HIV-DNA at T=4 weeks compared to T=0.
研究概览
简要总结
Primary objectives phase I: To assess the efficacy of 1-day dual LRA combinations treatment on HIV reservoir reactivation in PLWH. Primary objectives phase II: Efficacy of a 4-week dual LRA combination treatment on HIV reservoir reduction.
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
- •In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- •Documented HIV-1 infection, confirmed by Western Blot or PCR.
- •Age ≥ 18 years old.
- •Confirmed HIV1 subtype A, B, C or D. In case no HIV sequencing is available, proviral sequencing can be performed (preferably on left-over blood samples) to assess subtype. People with other HIV1 subtypes can only be included after discussion with Sponsor and is contingent on possible primary endpoint assay adaptation.
- •Uninterrupted ART therapy for a minimum 6 months.
- •Plasma HIV RNA ≤50 copies/ml prior to inclusion at two consecutive measurements at least three months apart.
- •No disclosed missed ART on more than 2 days per month.
- •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.
- •Able to understand provided information and to give informed consent.
排除标准
- •A potential subject who meets any of the following criteria will be excluded from participation in this study:
- •Prior exposure to any of the studied LRAs in the previous 90 days 33 of 69 Based on CCMO protocol template CTR Version 3.0, May 2023 2026-525211-14-00, 1.3 (30-01-2026) CONFIDENTIAL
- •HIV-2 (double)infection
- •Co-infection with hepatitis B, unless resolved HBV (anti-HBc positive, anti-HBs positive and HBsAg negative) OR HBsAg positive and on continuous HBV-active antiviral therapy for ≥24 weeks prior to dosing, and HBV DNA undetectable or ≤ 200 IU/mL on two measurements (screening and within 4 weeks prior to enrolment), and no history of advanced fibrosis/cirrhosis (stage F2 and higher)
- •Co-infection with hepatitis C, measured by the presence of hepatitis C virus RNA in blood.
- •Co-medication with clinically significant interactions with LRA.
- •mRNA vaccine or adjuvant vaccine (e.g. Shingrix) in the previous 4 weeks.
- •Megaloblastic anaemia due to folate deficiency and untreated haemolysis of any cause
- •Active malignancy during the past year with the exception of basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi’s sarcoma treated with ART alone or other indolent malignancies.
- •History of suicide attempt or suicidal ideation.
- •History of ophthalmological medical problems leading to glaucoma or visual field disturbances (e.g. macula oedema). Refraction abnormalities that can be corrected by lenses are acceptable.
- •History of any medical condition with a causal relationship with hyperammonaemia.
- •History of epileptic seizures in the previous year.
- •Registered allergies for any of the investigational medical products
- •Sexually active participants who do not fit any of the following: a) Female subject of childbearing potential willing to comply with pregnancy tests before start and four weeks after end of treatment and willing to use of double contraceptive measures during and until 1 week after administration of study medication. Non-childbearing is defined by one of the following criteria: amenorrhoea for ≥ 1 year, premature ovarian failure, assigned male at birth, or having undergone bilateral salpingo-oophorectomy, or hysterectomy. b) Sexually active male PLWH who have sex with female partners of childbearing potential and willing to abstain from sex or willing to use condom protection during and until 1 week after administration of study medication. c) Sexually active male PLWH who have sex with postmenopausal female partners and willing to abstain from sex or willing to use condom protection or with a postmenopausal female partner on pre-exposure prophylaxis during and until 1 week after administration of study medication. d) Male PLWH who have sex with male partners and willing to abstain from sex or willing to use a condom protection during and until 1 week after administration of study medication. e) Male PLWH who have sex with male partners on preexposure prophylaxis during and until 1 week after administration of study medication.
- •Any lab abnormalities at screening as listed below: a) Moderate kidney impairment, defined as eGFR <50 mL/min. In PLWH on dolutegravir- or bictegravir-based ART regimens, cystatin C-based eGFR can be used, since possible drug interference with tubular creatinine excretion which leads to eGFR underestimation. b) Moderate hepatic impairment, defined as bilirubin > 3 x upper limit of normal (ULN) or ALT > 3x ULN c) 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
研究组 & 干预措施
PYRIMETHAMINE
Test
干预措施: PYRIMETHAMINE (Drug)
TOPIRAMATE
Test
干预措施: TOPIRAMATE (Drug)
LENALIDOMIDE
Test
干预措施: LENALIDOMIDE (Drug)
结局指标
主要结局
Phase I : Fold change in cell-associated HIV-RNA at time points 6 (T=6) and 24 hours (T=24) after LRA treatment compared to baseline (T=0) before treatment. Phase II: Log transformed HIV-DNA at T=4 weeks compared to T=0.
Phase I : Fold change in cell-associated HIV-RNA at time points 6 (T=6) and 24 hours (T=24) after LRA treatment compared to baseline (T=0) before treatment. Phase II: Log transformed HIV-DNA at T=4 weeks compared to T=0.
次要结局
- Key secondary endpoint Phase I and phase II: The number and severity of clinical and biochemical adverse events using CTCAEv6.0.
- Phase I: Quantitative and qualitative patient reported outcomes of treatment satisfaction, QoL and stigma by validated questionnaires at T=0, T=24hr and T=7 days and by a semi-structured interview before the intervention and at T=24hr.
- Phase I: Change in plasma HIV-RNA between and within arms at T=6hr, T=24hr and T = 7 days compared to T=0.
- Phase I: The change of the frequency, functionality and phenotype of immune cell subpopulations; total T cells and HIV specific CD4+ and CD8+ T cells, B-cell differentiation, HIV specific B-cell clonotype and immunoglobulin sequence, and HIV specific antibody function, between and within the groups at T=7 days, compared to T=0.
- Phase I: Drug plasma levels of LRA compounds at T=0h, T= 6hr, T=24hr and T=7 days.
- Phase I: Drug plasma levels of ART at T=0hr, T=6hr, T=24hr and T=7 days.
- Phase I: The correlation between ex vivo and in vivo fold change in cell-associated HIV-RNA from T=0 to T=24hr.
- Phase II: Quantitative and qualitative patient reported outcomes of treatment satisfaction, QoL and stigma by questionnaires and by a semi-structured interview at T=0 to T=4 weeks.
- Phase II: Fold change cell associated HIV RNA from T=0 to T=24hr in participants in phase 2 com-pared to T=0 to T=24hr in participants in phase 1 overall and by prior LRA exposure.
- Phase II: Change in plasma HIV-RNA absolute copies/mL and proportion with viral target detectable, >30, >50, and >200 c/mL within group at T=24hr, T=1, 2, 3, and 4 weeks compared to T=0.
- Phase II: The change of the frequency, functionality and phenotype of immune cell subpopulations; total T cells and HIV specific CD4+ and CD8+ T cells, B-cell differentiation, HIV specific B-cell clonotype and immunoglobulin sequence, and HIV specific antibody function, at T=1 and T=4 weeks compared to T=0.
- Phase II: Drug plasma levels of LRA compounds at T=1, 2, 3, and 4 weeks.
- Phase II: Drug plasma of ART levels T=1, 2, 3, and 4 weeks.
- Phase II: The correlation between ex vivo and in vivo fold change in cell-associated HIV-RNA from T=0 to T=24hr overall and by prior LRA exposure.
研究者
Casper Rokx
Scientific
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
研究点 (6)
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