2024-518873-32-00招募中2 期
Administration of the BCL-2 antagonist, venetoclax, to promote apoptosis of HIV-infected cells and reduce the size of the HIV reservoir: An investigator-initiated phase I/IIb clinical trial in people living with HIV on antiretroviral therapy (The AMBER Study)
Aarhus University Hospital1 个研究点 分布在 1 个国家目标入组 27 人开始时间: 2024年10月23日最近更新:
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Safety defined as treatment-emerging adverse events (AEs) >=grade 3 (as cited as dose limiting toxicities section 4.2) probably or definitely related to study treatment
研究概览
简要总结
To determine the safety of venetoclax in PLWH on ART
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Documented HIV-1 infection
- •Heterosexually active male if they are o willing to use an effective method of contraception (anatomical sterility in self that is confirmed prior to study entry) or o agree on the use of an effective method of contraception with an effective failure rate of < 1% by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility) from the day prior to the first dose and for at least 2 weeks after discontinuation of study drug.
- •Age 18-65 years, both included
- •Receiving combination ART for at least 2 years and being on the same ART regimen for at least 4 weeks at the screening visit
- •HIV-1 plasma RNA <50 copies/mL for >2 years (documented on at least 2 occasions within the 2 years) and <20 copies/mL at screening. Episodes of a single HIV plasma RNA 50-500 copies/mL will not exclude participation if the subsequent HIV plasma RNA was <50 copies/mL
- •CD4+ T cell count >500 cells/μL at screening and at least two CD4+ T cell counts >500 cells/μL in the 24 months prior to screening
- •Ability and willingness to provide informed consent and to continue ART throughout the study
- •For potential study participants who anticipate receiving a SARS-CoV-2 vaccine within the study period, enrolment and commencement of study therapy will be postponed until 4 weeks after completing SARS-CoV-2 vaccination, whereas screening procedures can be initiated before or concurrently with SARS-CoV-2 vaccination.
- •A female, may be eligible to enter and participate in the study if she: o Is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, o Is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the specified methods of contraception to avoid pregnancy
- •All participants must agree not to participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) during the study
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study. Study participants receiving cobicistat or a protease inhibitor may opt to switch their ART regimen away from those drugs to allow study participation if this is deemed reasonable by their treating physician but will need to maintain their new regimen for at least 4 weeks prior to enrolling in the study.
- •Known hypersensitivity to the components of venetoclax or its analogues
- •Any significant acute medical illness in the past 4 weeks
- •Any evidence of an active AIDS-defining opportunistic infection
- •Individuals who intend to modify their ART regimen within the study period
- •Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
- •Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
- •Unable or unwilling to adhere to protocol procedures
- •History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
- •Co-infection with hepatitis B or C (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)
- •Impaired liver function with AST or ALT >3 times upper limit of normal
- •Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy
- •Severe hepatic impairment (Class C) as determined by Child-Pugh classification
- •Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min
- •Significant cardiac dysfunction
- •Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy as specified in the inclusion criteria
- •The specified laboratory values at screening (lab tests may be repeated, as clinically indicated, to obtain acceptable values before failure at screening is concluded but supportive therapies are not to be administered within the week prior to screening tests)
- •Any concomitant disease where venetoclax treatment is indicated
- •Current use of any moderate or strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin)
- •Current use of any HIV protease inhibitor (due to CYP3A4 inhibition)
- •Current use of any strong inhibitor of the P-gp drug efflux pump (this includes cobicistat, ritonavir, azithromycin and clarithromycin)
- •Current use of strong CYP3A4 inducers (such as carbamazepine, phenytoin, rifampicin and St. John’s wort); moderate CYP3A4 inducers (such as bosentan, efavirenz, etravirine, modafinil and nafcillin) may be used but should be avoided as much as possible
- •Receipt of immunomodulating agents (excluding immunisation) or systemic chemotherapeutic agents within 28 days prior to study entry
- •Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
结局指标
主要结局
Safety defined as treatment-emerging adverse events (AEs) >=grade 3 (as cited as dose limiting toxicities section 4.2) probably or definitely related to study treatment
Safety defined as treatment-emerging adverse events (AEs) >=grade 3 (as cited as dose limiting toxicities section 4.2) probably or definitely related to study treatment
Safety defined as all other treatment-emerging AEs, graded according to severity and assessed as either not related or possibly, probably or definitely related to study treatment
Safety defined as all other treatment-emerging AEs, graded according to severity and assessed as either not related or possibly, probably or definitely related to study treatment
次要结局
未报告次要终点
研究者
Jesper D. Gunst
Scientific
Aarhus University Hospital
研究点 (1)
Loading locations...
相似试验
招募中
1 期
Administration of Venetoclax to Promote Apoptosis of HIV-infected Cells and Reduce the Size of the HIV Reservoir Among People Living With HIV on ARTHIV-1-infectionNCT05668026University of Aarhus18
撤回
2 期
A Study of Venetoclax Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose TherapyMultiple MyelomaNCT03785184AbbVie
招募中
1 期
A Study on the Efficacy and Safety of Venetoclax Combined With HAA Regimen in Newly Diagnosed Young AML.VenetoclaxAcute Myeloid LeukemiaNCT05893472ZePing Zhou45
已完成
1 期
Study Evaluating Venetoclax in Subjects With Hematological MalignanciesNon-Hodgkin Lymphoma (NHL)Multiple Myeloma (MM)Chronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)Acute Myeloid Leukemia (AML)NCT02265731AbbVie38
招募中
2 期
Clinical Study of Venetoclax Combined With CAG in the Treatment of Refractory/Relapsed Acute Myeloid LeukemiaAcute Myeloid LeukemiaNCT05918198Peking University People's Hospital52