NCT07053384进行中（未招募）1 期
An Exploratory Phase 1b, Multicenter, Randomized, Open-Label Study to Investigate the Impact of the Administration of Intravenous VH3810109 With or Without Oral Fostemsavir in Combination With Integrase Inhibitor-Based Antiretroviral Therapy on the Viral Reservoir in Adults Living With HIV-1
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 130
- 试验地点
- 41
- 主要终点
- Change from baseline in cell-associated HIV-1 RNA transcripts per million cluster of differentiation 4 (CD4+) T cells
研究概览
简要总结
This study investigates the use of VH3810109 with or without FTR to reduce the size and activity of the HIV viral reservoir in two sub-populations of people living with HIV: treatment-naïve adults (Population 1) and treatment-experienced adults currently taking a standard of care (SOC) integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen (Population 2). The study is designed to include the following phases: Randomized Intervention Phase (Step 1), Analytical Treatment Interruption (ATI) Phase (Step 2), and Follow-up Phase (Step 3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 years and 70 years old at the time of obtaining informed consent.
- •SEX AND GENDER • Persons of any sex or gender are eligible. Note: Participants of childbearing potential (POCBP) are eligible to participate if not pregnant, not lactating, and agreeing to adhere to study requirements for use of contraception and pregnancy avoidance.
- •PARTICIPANT KEY CHARACTERISTICS • Participant has a documented diagnosis of HIV-1 infection. Note: Participants in Population 1 must have a documented positive HIV antibody result available for Screening.
- •Population 1 only:
- •Plasma HIV-1 RNA >=2000 copies/milliliter (c/mL) at Screening.
- •CD4+ T cell count >=300 cells/microliter (μL) at Screening.
- •Antiretroviral treatment naïve, defined as no exposure to ART after a diagnosis of HIV-1 infection, prior to enrollment.
- •Population 2 only:
- •Participant is stably virologically suppressed (plasma HIV-1 RNA <50 c/mL).
- •Documented evidence of uninterrupted treatment with oral non-boosted INSTI-based ART for at least 6 months prior to Screening, as well as uninterrupted treatment with ART (any guideline-recommended oral regimen) for at least 24 months prior to Screening.
- •CD4+ T cell count >=450 cells/μL at Screening.
- •Body weight >=50 kg to <=115 kg.
- •INFORMED CONSENT • Participant is capable of giving written informed consent, which includes adherence to the requirements and restrictions listed in the consent form and in the protocol.
排除标准
- •CONCURRENT MEDICAL CONDITIONS & MEDICAL HISTORY
- •Participant is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study.
- •Participant has documented diagnosis of HIV-2 infection.
- •Participant is known to have acquired HIV via perinatal transmission.
- •Any evidence of a current or known past Center for Disease Control and Prevention (CDC) Stage 3 disease.
- •Any ongoing malignancy or history of systemic cancers, such as Kaposi's sarcoma and lymphoma, or other virus-associated malignancies.
- •Ongoing or clinically relevant pancreatitis.
- •Current HIV-related kidney disease.
- •History of or active HIV-associated dementia or progressive multifocal leukoencephalopathy.
- •CARDIAC & CARDIOVASCULAR CONDITIONS
- •Participants who are at clinically significant risk of cardiovascular disease.
- •Ongoing or any lifetime history of clinically significant cardiovascular or cardiac disease.
- •Confirmed QTcF value outside normal range at Screening or Day
- •HEPATIC CONDITIONS
- •History of clinically relevant hepatitis in the 6 months prior to Screening.
- •Participants with severe hepatic impairment.
- •Advanced MAFLD and advanced non-alcoholic steatohepatitis, if evidence for substantial fibrosis (fibrosis score ≥F2) or evidence of cirrhosis.
- •Unstable liver disease.
- •History of liver cirrhosis with or without hepatitis viral co-infection.
- •NEUROPSYCHIATRIC CONDITIONS • Participants who pose a significant suicide risk.
- •LABORATORY DIAGNOSTIC ASSESSMENTS
- •Participants who are experiencing (Population 1) or are known to have initiated ART during (Population 2) acute HIV infection.
- •Any verified Grade 4 laboratory abnormality at Screening, excluding asymptomatic elevations of lipids or CPK.
- •Alanine transferase (ALT) >=3 times the upper limit of normal (ULN) at Screening.
- •Estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m^
- •Hemoglobin >=Grade 2 at Screening.
- •Platelets >=Grade 2 at Screening.
- •Absolute Neutrophil Count (ANC) ≥Grade 2 at Screening.
- •Any acute abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's inclusion in an interventional clinical study.
- •Population 2 only:
- •Two or more plasma HIV-1 RNA results >=50 c/mL in the 18 months prior to Screening.
- •INFECTIOUS DISEASES
- •Active hepatitis B virus (HBV) co-infection.
- •Active hepatitis C virus (HCV) co-infection.
- •Participant has untreated syphilis before enrolment.
- •Known history of active Mycobacterium TB disease (regardless of treatment status).
- •ANTIRETROVIRAL RESISTANCE • Known major resistance-associated mutations to second-generation INSTIs or to antiretroviral (ARV) agents from 2 or more drug classes.
- •PRIOR AND CONCOMITANT MEDICATIONS
- •Prior use of any of the following agents:
- •- long-acting ARVs (any dose in the past 24 months or within 5 half-lives [whichever is longer])
- •- FTR (any lifetime use)
- •- HIV-1 immunotherapeutic vaccines or prophylactic vaccines (any lifetime use)
- •- HIV-1 monoclonal antibody therapy (any lifetime use).
- •Prior receipt of any approved or experimental non-HIV vaccination within 2 weeks prior to study enrolment.
- •History of systemic corticosteroids, immunosuppressive anti-cancer, interleukins, systemic interferons, or systemic chemotherapy, within 6 months prior to Screening.
- •Participant has received an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent (whichever is longer), prior to enrolment.
- •Treatment with any of the following agents within 30 days of enrolment:
- •- radiation therapy
- •cytotoxic chemotherapeutic agents
- •anti-tuberculosis therapy
- 另有 12 项未显示
结局指标
主要结局
Change from baseline in cell-associated HIV-1 RNA transcripts per million cluster of differentiation 4 (CD4+) T cells
时间窗: From Baseline (Day 1) to Month 12
Randomized Intervention Phase (Step 1): Change from baseline in cell-associated HIV-1 RNA transcripts per million cluster of differentiation 4 (CD4+) T cells
时间窗: From Baseline (Day 1) to Month 12
次要结局
- Change from baseline in total, intact, and defective proviral HIV-1 DNA per million CD4+ T cells(From Baseline (Day 1) to Month 12)
- Absolute change in cell-associated HIV-1 RNA/proviral DNA ratios in CD4+ T cells(From Baseline (Day 1) to Month 12)
- Absolute values for p24+ CD4+ T cell count(From Baseline (Day 1) to Month 12)
- Change from baseline in number of p24+ CD4+ T cells(From Baseline (Day 1) to Month 12)
- Absolute values for HIV-1-specific CD8+ T cell count(From Baseline (Day 1) to Month 12)
- Change from baseline in HIV-1-specific CD8+ T cell count(From Baseline (Day 1) to Month 12)
- Number of participants with Grade 3 and Grade 4 adverse events (AEs)(From Baseline (Day 1) to Month 12)
- Number of participants with serious adverse events (SAEs), deaths and AEs leading to discontinuation of study intervention(From Baseline (Day 1) to Month 12)
- Randomized Intervention Phase (Step 1): Change from baseline in total, intact, and defective proviral HIV-1 DNA per million CD4+ T cells(From Baseline (Day 1) to Month 12)
- Randomized Intervention Phase (Step 1): Absolute change in cell-associated HIV-1 RNA/proviral DNA ratios in CD4+ T cells(From Baseline (Day 1) to Month 12)
- Randomized Intervention Phase (Step 1): Absolute values for HIV-1-specific CD8+ T cell count(From Baseline (Day 1) to Month 12)
- Randomized Intervention Phase (Step 1): Change from baseline in HIV-1-specific CD8+ T cell count(From Baseline (Day 1) to Month 12)
- Randomized Intervention Phase (Step 1): Number of participants with Grade 3 and Grade 4 adverse events (AEs)(From Baseline (Day 1) to Month 15)
- Randomized Intervention Phase (Step 1): Number of participants with serious adverse events (SAEs), deaths and AEs leading to discontinuation of study intervention(From Baseline (Day 1) to Month 15)
- ATI Phase (Step 2): Time to ART restart(From Day 1A to Week 24A (ATI Phase Alpha) and Week 48A (ATI Phase Gamma))
- ATI Phase (Step 2): Number of participants with Grade 3 and Grade 4 AEs(From Day 1A to Week 24A (ATI Phase Alpha) and Week 48A (ATI Phase Gamma))
- ATI Phase (Step 2): Number of participants with SAEs and deaths(From Day 1A to Week 24A (ATI Phase Alpha) and Week 48A (ATI Phase Gamma))
- ATI Phase (Step 2): Number of participants with disease progression (HIV-associated conditions, acquired immunodeficiency syndrome [AIDS] and death)(From Day 1A to Week 24A (ATI Phase Alpha) and Week 48A (ATI Phase Gamma))
研究者
研究点 (41)
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