2025-521841-26-00招募中2 期
Inhibiting the anti-apoptotic factor, BCL-2, at the time of ART initiation to promote apoptosis of HIV-infected cells and restrict the seeding of the HIV reservoir: An investigator-initiated randomised, controlled, open-label clinical trial (The INITIATE Study)
Region Midtjylland4 个研究点 分布在 1 个国家目标入组 26 人开始时间: 2026年1月2日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- Primary safety endpoint: Safety defined as treatment-emerging adverse events (AEs) related to study treatment (from Day 0 to Day 365)
研究概览
简要总结
To determine the safety of venetoclax administration in PLWH at the time of ART initiation
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
- 是
入选标准
- •Documented HIV-1 infection
- •All participants must agree to use condoms during all sexual intercourse in situations where HIV transmission may still occur, i.e. until fully suppressed on ART (plasma HIV-1 RNA <50 copies/mL)
- •Age 18-70 years (both included) at screening
- •CD4+ T cell count >300/µL at screening
- •ART naïve at screening
- •Able to give informed consent
- •Ability and willingness to provide informed consent and to continue ART throughout the study
- •A female, may be eligible to enter and participate in the study if she: - 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, - Is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy: Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject Approved hormonal contraception (Where other medications to be used in the study (e.g., efavirenz and darunavir) are known, or are likely, to significantly interact with systemic contraceptives, resulting in decreased efficacy of the contraceptive, then alternative methods of non-hormonal contraception are recommended) Any other method with published data showing that the expected failure rate is <1% per year Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of study therapy.
- •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
- •Heterosexually active male if they are - willing to use an effective method of contraception (anatomical sterility in self that is confirmed prior to study entry) or - 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 4 weeks after discontinuation of study drug.
排除标准
- •Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy
- •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
- •Known hypersensitivity to the components of venetoclax or its analogues
- •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 defined as HBsAg-positive or Hepatitis C defined as HCV-RNA positive (Individuals with prior hepatitis B or C infection that is now cleared are eligible for enrolment); For individuals with isolated anti-HBcAb (cleared hepatitis B), the chosen ART regimen must include TDF or TAF
- •Impaired liver function with AST or ALT >3 times upper limit of normal
- •Evidence of or strong suspicion that HIV infection was acquired during active PrEP use
- •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 following 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): - Platelet count ≤100 x109/L - Absolute neutrophil count ≤1.0x109/L - Haemoglobin <10,0 g/dL - CD4+ T cell count <300 cells/uL
- •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 P-gp substrates with narrow therapeutic index (such as such as digoxin, tacrolimus, cyclosporine, sirolimus, dabigatran, colchicine, loperamide)
- •Current use of strong or moderate CYP3A4 inducers (such as carbamazepine, phenytoin, rifampicin, St. John’s wort, bosentan, efavirenz and etravirine); intermittent use of moderate CYP3A4 inducers such as 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
结局指标
主要结局
Primary safety endpoint: Safety defined as treatment-emerging adverse events (AEs) related to study treatment (from Day 0 to Day 365)
Primary safety endpoint: Safety defined as treatment-emerging adverse events (AEs) related to study treatment (from Day 0 to Day 365)
Primary effect endpoint: The frequency of peripheral blood CD4+ T cells containing intact HIV-DNA at day 365 using the Cross-Subtype Intact Proviral DNA Assay (IPDA)
Primary effect endpoint: The frequency of peripheral blood CD4+ T cells containing intact HIV-DNA at day 365 using the Cross-Subtype Intact Proviral DNA Assay (IPDA)
次要结局
- Safety defined as all other treatment-emerging AEs, graded according to severity and assessed as either not related or related to study treatment (from Day 0 to Day 365)
- Decay rates of plasma HIV RNA following initiation of ART
- Levels of CD4+ T cells expressing intracellular p24 quantified by flow cytometry
- The frequency of peripheral blood CD4+ T cells containing total HIV-DNA using real-time or digital droplet PCR
- The proportion of cells containing constitutive and inducible cell-associated multiply spliced HIV RNA (MS HIV-RNA) at day 365 using the tat/rev induced limiting dilution assay (TILDA)
- The level of cell-associated unspliced HIV RNA (CA-US HIV RNA) in peripheral blood CD4+ T cells using real-time or digital droplet PCR
- Changes in numbers and proportions of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets (from Day 0 to Day 365)
- The ratio of intact and total HIV-DNA in peripheral blood CD4+ T cells (from Day 0 to Day 365)
研究者
Thomas A. Rasmussen
Scientific
Region Midtjylland
研究点 (4)
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