NCT02411539已完成1 期
A Phase I Study to Evaluate the Safety, Tolerability, and Effect of a Human Monoclonal Antibody, VRC-HIVMAB060-00-AB (VRC01), on Markers of HIV Persistence in ART-treated, HIV-infected Adults
National Institute of Allergy and Infectious Diseases (NIAID)26 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2015年8月25日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 26
- 主要终点
- Number of Participants Who Experienced Grade 3 or Greater, Treatment Related, Adverse Event (AE)
研究概览
简要总结
The purpose of this study was to evaluate the safety, tolerability, and effect of an experimental human monoclonal antibody (mAb), VRC-HIVMAB060-00-AB (VRC01), in adults infected with HIV who were receiving antiretroviral therapy (ART).
详细描述
Monoclonal antibodies (mAbs) have been developed as treatment for a variety of conditions including cancer, autoimmune disorders, and infections. mAbs may also be a potential treatment for people infected with HIV. The purpose of this study was to evaluate the safety and tolerability of an experimental human mAb, VRC-HIVMAB060-00-AB (VRC01), in HIV-infected adults receiving ART. Study researchers will also evaluate the effect of VRC01 on the number of infected cells containing unspliced HIV-1 transcripts in the blood in participants.
This study enrolled HIV-infected people 18 to 65 years old, who had been receiving ART for at least 2 years and who had a CD4+ count of 200 cells/mm^3 or greater. Participants were randomly assigned to Arm A or Arm B. Participants in Arm A received an intravenous (IV) infusion of VRC01 at Day 0 and Week 3 and an IV infusion of placebo (normal saline) at Weeks 6 and 9. Participants in Arm B received an IV infusion of placebo (normal saline) at Day 0 and Week 3 and an IV infusion of VRC01 at Weeks 6 and 9. Participants recorded their temperature and symptoms for 3 days after each infusion. Study visits occured at study entry (Day 0), and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, and 30. Study visits included physical examinations, clinical assessments, and blood collection.
The primary safety outcome for this study was descriptive and assessed the occurrence of Grade ≥ 3 AEs including signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment (as judged by the core team, blinded to treatment arm) at any time from the initial dose of study treatment to the end of study follow-up. Since this outcome is descriptive, no statistical significance testing was performed.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infection, documented by any FDA-approved rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV or E/CIA tests, or by HIV-1 antigen, or plasma HIV-1 RNA assay. More information on this criterion is available in the protocol.
- •Received continuous ART for at least 2 years (defined as no interruptions longer than 14 consecutive days) and with no changes in the components of the ART for at least 90 days prior to study entry
- •CD4+ cell count greater than or equal to 200 cells/mm^3 obtained within 60 days prior to study entry in a clinical laboratory improvement amendments (CLIA)-certified laboratory
- •Plasma HIV-1 RNA below the limit of detection of the FDA-approved assays (limit of detection: 75, 50, 40 or 20 copies/mL) for greater than or equal to 2 years on ART. Participants must have had at least one documented HIV-1 RNA less than the limit of detection 12-24 months prior to study entry and at least one HIV-1 RNA less than the limit of detection within 12 months prior to study entry. All available HIV-1 RNA measurements must have been below the assay limit of detection during the 2 years prior to study entry except as allowed by the following note. NOTE: A single unconfirmed plasma HIV-1 RNA greater than the limit of detection but less than 200 copies/mL within 6-24 months was allowed if followed by a subsequent value below the limit of detection.
- •Plasma HIV-1 RNA level of less than 40 copies/mL obtained by the Abbott Real-time HIV assay (m2000) or less than 20 copies/mL obtained by the Roche COBAS Taqman HIV-1 v2.0 assay within 60 days prior to entry
- •The following laboratory values obtained within 60 days prior to entry by any U.S. laboratory that has a CLIA certification or its equivalent.
- •Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
- •Hemoglobin greater than or equal to 11.0 g/dL for men and greater than or equal to 10.0 g/dL for women
- •Platelet count greater than or equal to 100,000/mm^3
- •Creatinine clearance greater than or equal to 60 mL/min estimated by the Cockcroft-Gault equation. NOTE: A program for calculating creatinine clearance by the Cockcroft-Gault method is available on www.fstrf.org.
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (SGPT) less than or equal to 2.0 times upper limit of normal (ULN)
- •Hepatitis C virus (HCV) antibody negative result within 60 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result within 60 days prior to study entry
- •Negative HBsAg result obtained within 60 days prior to study entry
- •Ability and willingness of participant to provide informed consent
- •Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or bilateral salpingectomy), needed a negative serum or urine pregnancy test within 48 hours prior to study entry. NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, bilateral salpingectomy, tubal micro-inserts, partner who has undergone vasectomy, and menopause is participant-reported history.
- •All participants must have agreed not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least one reliable form of contraception (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine device (IUD); or hormone-based contraceptive), while receiving study treatment and for 12 weeks after stopping study treatment
- •Documentation of the availability of the following stored samples from the screening visit: peripheral blood mononuclear cell (PBMC) for CD4+ T-cell associated HIV-1 RNA, DNA assay and plasma for HIV-1 SCA. Sites must receive confirmation from the processing lab via phone, email, or fax, that specimens have been entered into the AIDS Clinical Trials Group (ACTG) Laboratory Data Management System (LDMS).
排除标准
- •Previous receipt of humanized or human monoclonal antibody (licensed or investigational)
- •Weight greater than 115 kg or less than 53 kg
- •Acute or ongoing AIDS-defining illness within 60 days prior to study entry
- •History of a severe allergic reaction with generalized urticarial, angioedema, or anaphylaxis within 2 years of study entry
- •Currently breastfeeding or pregnant
- •Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
- •Acute or serious illness that, in the opinion of the site investigator, requires systemic treatment and/or hospitalization within 60 days prior to entry
- •Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry. NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone less than or equal to 10 mg/day, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids will not be excluded.
- •Treatment for hepatitis C within 24 weeks of study entry
- •Vaccinations within 7 days prior to the screening, pre-entry, or study entry visits. NOTE: Participants are encouraged to get routine vaccinations, such as seasonal influenza vaccine more than 7 days prior to screening or between screening and pre-entry visits (outside of the 7-day window above).
- •Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records)
结局指标
主要结局
Number of Participants Who Experienced Grade 3 or Greater, Treatment Related, Adverse Event (AE)
时间窗: Measured from study treatment initiation to study discontinuation (study duration is 30 weeks)
Refer to detailed description in the protocol section. Includes signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment (as judged by the core team, blinded to treatment arm) at any time from the initial dose of VRC01 to end of study follow-up. This analysis was primarily descriptive and no significance testing was performed.
Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells
时间窗: Screening, entry and week 6
Change from baseline (geometric average of screening and entry results) to week 6 in log10 transformed cell-associated HIV-1 RNA/DNA ratio in total CD4+ cells
次要结局
- Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Across Arms(Screening, entry and weeks 6 and 12)
- Plasma Levels of sCD14(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Plasma Levels of Human Soluble Tumor Necrosis Factor Alpha-receptor (sTNFαR)(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells(Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Total/Inducible Virus Recovery - Unstimulated Cell Fluor(Measured at pre-entry, week 6 and week 12)
- Change in Total/Inducible Virus Recovery - Stimulated Cell Fluor(Measured at pre-entry, week 6)
- Plasma Levels of Interleukin-6 (IL-6)(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Plasma Levels of Tumor Necrosis Factor Alpha (TNFα)(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Number of Participants With Premature Treatment Discontinuation, for Reasons Related to Study Treatment(Measured from study treatment initiation to study treatment discontinuation (study treatment dispensed through week 12))
- Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Last Value Carried Forward (LVCF)(Screening, entry, week 3 and week 6 (week 3 used as LVCF if necessary))
- Cell-associated HIV-1 RNA in Total CD4+ Cells(Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Cell-associated HIV-1 DNA in Total CD4+ Cells(Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- CD4+ T-cell Counts(Measured at screening, entry and weeks 6, 12, 18 and 30)
- Total/Inducible Virus Recovery - Stimulated Cell Fluor(Measured at pre-entry, week 6 and week 12)
- Change in Total/Inducible Virus Recovery - Unstimulated Cell Fluor(Measured at pre-entry, week 6)
- Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio(Measured at pre-entry, week 6)
- VRC01 Antibody Level(Measured at entry and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18 and 30)
- Detectability of Antibody to VRC01 as Measured in Serum(Measured at week 30)
- Total/Inducible Virus Recovery - Percentage of Total CD4 Yield(Measured at pre-entry, week 6 and week 12)
- Number of Participants With Plasma HIV-1 RNA by Single Copy Assay (SCA) Below Assay Lower Limit(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- CD8+ T-cell Counts(Measured at screening, entry and weeks 6, 12, 18 and 30)
- Total/Inducible Virus Recovery - Stimulated HIV-1 RNA(Measured at pre-entry, week 6 and week 12)
- Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA(Measured at pre-entry, week 6 and week 12)
- Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio(Measured at pre-entry, week 6 and week 12)
- Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio(Measured at pre-entry, week 6 and week 12)
- Change in Total/Inducible Virus Recovery - Stimulated HIV-1 RNA(Measured at pre-entry, week 6)
- Change in Total/Inducible Virus Recovery - Percentage of Total CD4 Yield(Measured at pre-entry, week 6)
- Levels of NK Cell Activation(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Plasma Levels of High-sensitivity C-reactive Protein (hsCRP)(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Change in Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA(Measured at pre-entry, week 6)
- Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio(Measured at pre-entry and week 6)
- Levels of T-cell Activation(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- Plasma Levels of sCD163(Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30)
- VRC01 Antibody Level Relative to Infusion Timing(Measured immediately after first infusion (and 1, 2, and 3 weeks after), and immediately after second infusion (and 1, 2, 3, 6 and 9 weeks after))
研究者
研究点 (26)
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