Evaluating the Safety, Tolerability, and Effect of a Human Monoclonal Antibody (VRC01) on Markers of HIV Persistence in HIV-Infected Adults Receiving Antiretroviral Therapy (ART)
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VRC01
Placebo
Sponsored by

About this trial
This is an interventional treatment trial for HIV Infections focused on measuring HIV, VRC01
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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)
Sites / Locations
- UCSD Antiviral Research Center CRS
- University of Colorado Hospital CRS
- Northwestern University CRS
- Johns Hopkins University CRS
- Massachusetts General Hospital CRS (MGH CRS)
- Washington University Therapeutics (WT) CRS
- University of Rochester Adult HIV Therapeutic Strategies Network CRS
- Chapel Hill CRS
- Ohio State University CRS
- University of Pittsburgh CRS
- Vanderbilt Therapeutics (VT) CRS
- Houston AIDS Research Team CRS
- University of Washington AIDS CRS
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A: VRC01 followed by placebo
Arm B: placebo followed by VRC01
Arm Description
Participants received an infusion of VRC01 at Day 0 and Week 3 and an infusion of placebo (normal saline) at Weeks 6 and 9.
Participants received an infusion of placebo (normal saline) at Day 0 and Week 3 and an infusion of VRC01 at Weeks 6 and 9.
Outcomes
Primary Outcome Measures
Number of Participants Who Experienced Grade 3 or Greater, Treatment Related, Adverse Event (AE)
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
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
Secondary Outcome Measures
Number of Participants With Premature Treatment Discontinuation, for Reasons Related to Study Treatment
Study treatment was taken from entry through week 12 - this outcome assesses the number of participants who permanently and prematurely discontinued study treatment due to reasons related to the study treatment
Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Last Value Carried Forward (LVCF)
Change from baseline (geometric average of screening and entry results) to week 6 in cell-associated HIV-1 RNA/DNA ratio in total CD4+ cells, using a last value carried forward approach if week 6 cell-associated HIV-1 RNA/DNA ratio was missing. In the event that the week 6 value was missing, the week 3 value was carried forward to be used. This comparison is the change from the average of screening and entry results to the week 6 value (if available), and if week 6 result was not available, the week 3 value was used instead of the week 6 value.
Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Across Arms
Summary of within-participant change across treatment arms from the pre-VRC01 time point to the post-VRC01 time point. For Arm A, the pre-VRC01 time point used was the baseline measure (geometric average of screening and entry results) and the post-VRC01 time point was the week 6 measure. For Arm B, the pre-VRC01 time point used was the week 6 measure and the post-VRC01 time point was the week 12 measure. Change in CA-RNA/DNA ratio was calculated on the log10 scale.
Cell-associated HIV-1 RNA in Total CD4+ Cells
Testing priority was given to samples from screening, entry and weeks 3, 6, 9 and 12. Baseline values are the geometric mean of screening and entry results. Testing of specimens at weeks 1, 4, 7, 10, 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
Cell-associated HIV-1 DNA in Total CD4+ Cells
Testing priority was given to samples from screening, entry and weeks 3, 6, 9 and 12. Baseline values are the geometric mean of screening and entry results. Testing of specimens at weeks 1, 4, 7, 10, 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells
Testing priority was given to samples from screening, entry and weeks 3, 6, 9 and 12. Baseline values are the geometric mean of screening and entry results. Testing of specimens at weeks 1, 4, 7, 10, 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
Number of Participants With Plasma HIV-1 RNA by Single Copy Assay (SCA) Below Assay Lower Limit
The analysis of HIV-1 RNA SCA assessed the number of participants below the assay lower limit (1 copy/mL) at each measurement week. Specific specimens and time points were targeted based on Arm. Samples were not tested for Arm A at the Week 7 and Week 10 time points. Samples were not tested for Arm B at the Week 1 and Week 4 time points.
Testing of specimens at weeks 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
CD4+ T-cell Counts
Baseline measure represents the average of screening and entry results
CD8+ T-cell Counts
Baseline measure represents the average of screening and entry results
Total/Inducible Virus Recovery - Stimulated HIV-1 RNA
As part of the total virus recovery assay, results for stimulated HIV-1 RNA (copies/mL) are generated
Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA
As part of the total virus recovery assay, results for unstimulated HIV-1 RNA (copies/mL) are generated
Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio
As part of the total virus recovery assay, results for stimulated and unstimulated HIV-1 RNA (copies/mL) are generated. At each time point, the ratio of the stimulated to unstimulated HIV-1 RNA was calculated.
Total/Inducible Virus Recovery - Stimulated Cell Fluor
As part of the total virus recovery assay, results for stimulated cell fluor (light units) are generated.
Total/Inducible Virus Recovery - Unstimulated Cell Fluor
As part of the total virus recovery assay, results for unstimulated cell fluor (light units) are generated.
Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio
As part of the total virus recovery assay, results for stimulated and unstimulated cell fluor (light units) are generated. At each time point, the ratio of the stimulated to unstimulated cell fluor was calculated.
Total/Inducible Virus Recovery - Percentage of Total CD4 Yield
As part of the total virus recovery assay, results for %tCD4 yield are generated.
Change in Total/Inducible Virus Recovery - Stimulated HIV-1 RNA
As part of the total virus recovery assay, results for stimulated HIV-1 RNA (copies/mL) are generated. The change from the pre-treatment time point to week 6 was assessed as a fold change (week 6 / pre-entry)
Change in Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA
As part of the total virus recovery assay, results for unstimulated HIV-1 RNA (copies/mL) are generated. The change from the pre-treatment time point to week 6 was assessed as a fold change (week 6 / pre-entry)
Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio
As part of the total virus recovery assay, results for stimulated and unstimulated HIV-1 RNA (copies/mL) are generated. At each time point, the ratio of the stimulated to unstimulated HIV-1 RNA was calculated. The fold change of this ratio from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Change in Total/Inducible Virus Recovery - Stimulated Cell Fluor
As part of the total virus recovery assay, results for stimulated cell fluor (light units) are generated. The fold change from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Change in Total/Inducible Virus Recovery - Unstimulated Cell Fluor
As part of the total virus recovery assay, results for unstimulated cell fluor (light units) are generated. The fold change from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio
As part of the total virus recovery assay, results for stimulated and unstimulated cell fluor (light units) are generated. At each time point, the ratio of the stimulated to unstimulated cell fluor was calculated. The fold change of this ratio from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Change in Total/Inducible Virus Recovery - Percentage of Total CD4 Yield
As part of the total virus recovery assay, results for %tCD4 yield are generated. The fold change from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
VRC01 Antibody Level
Summarize the pharmacokinetics (PK) of two infusions of VRC01 during study follow up
Specific specimens and time points were targeted for testing based on Arm. Samples for Arm A were not tested for the Week 6 and Week 9 post-infusion time points. Samples for Arm B were not tested for the Week 0 and Week 3 post-infusion time points.
Detectability of Antibody to VRC01 as Measured in Serum
Assess the detectability of antibody to VRC01 in samples collected during study follow-up. Intended to be result from specimen at week 30 time point. Due to specimen availability, four participants in Arm A had results from specimens from the week 18 time point. Counts provided are number of participants with detectable anti-VRC01 antibody result.
Levels of T-cell Activation
% CD4+ and CD8+ T-cells co-expressing human leukocyte antigen (HLA)-DR and CD38
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Levels of NK Cell Activation
% NK cells expressing CD69 or CD95
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Plasma Levels of sCD163
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Plasma Levels of sCD14
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Plasma Levels of Interleukin-6 (IL-6)
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Plasma Levels of Human Soluble Tumor Necrosis Factor Alpha-receptor (sTNFαR)
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Plasma Levels of Tumor Necrosis Factor Alpha (TNFα)
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Plasma Levels of High-sensitivity C-reactive Protein (hsCRP)
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
VRC01 Antibody Level Relative to Infusion Timing
Summarize the pharmacokinetics (PK) of two infusions of VRC01 during study follow up - aligning the timing of PK samples/results to the respective VRC01 infusions for each Arm
Full Information
NCT ID
NCT02411539
First Posted
April 2, 2015
Last Updated
November 4, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
AIDS Clinical Trials Group
1. Study Identification
Unique Protocol Identification Number
NCT02411539
Brief Title
Evaluating the Safety, Tolerability, and Effect of a Human Monoclonal Antibody (VRC01) on Markers of HIV Persistence in HIV-Infected Adults Receiving Antiretroviral Therapy (ART)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
August 25, 2015 (Actual)
Primary Completion Date
April 15, 2016 (Actual)
Study Completion Date
September 29, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
AIDS Clinical Trials Group
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV, VRC01
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: VRC01 followed by placebo
Arm Type
Experimental
Arm Description
Participants received an infusion of VRC01 at Day 0 and Week 3 and an infusion of placebo (normal saline) at Weeks 6 and 9.
Arm Title
Arm B: placebo followed by VRC01
Arm Type
Experimental
Arm Description
Participants received an infusion of placebo (normal saline) at Day 0 and Week 3 and an infusion of VRC01 at Weeks 6 and 9.
Intervention Type
Biological
Intervention Name(s)
VRC01
Other Intervention Name(s)
VRC-HIVMAB060-00-AB
Intervention Description
40 mg/kg of VRC01 administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Normal saline administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
Primary Outcome Measure Information:
Title
Number of Participants Who Experienced Grade 3 or Greater, Treatment Related, Adverse Event (AE)
Description
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.
Time Frame
Measured from study treatment initiation to study discontinuation (study duration is 30 weeks)
Title
Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells
Description
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
Time Frame
Screening, entry and week 6
Secondary Outcome Measure Information:
Title
Number of Participants With Premature Treatment Discontinuation, for Reasons Related to Study Treatment
Description
Study treatment was taken from entry through week 12 - this outcome assesses the number of participants who permanently and prematurely discontinued study treatment due to reasons related to the study treatment
Time Frame
Measured from study treatment initiation to study treatment discontinuation (study treatment dispensed through week 12)
Title
Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Last Value Carried Forward (LVCF)
Description
Change from baseline (geometric average of screening and entry results) to week 6 in cell-associated HIV-1 RNA/DNA ratio in total CD4+ cells, using a last value carried forward approach if week 6 cell-associated HIV-1 RNA/DNA ratio was missing. In the event that the week 6 value was missing, the week 3 value was carried forward to be used. This comparison is the change from the average of screening and entry results to the week 6 value (if available), and if week 6 result was not available, the week 3 value was used instead of the week 6 value.
Time Frame
Screening, entry, week 3 and week 6 (week 3 used as LVCF if necessary)
Title
Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Across Arms
Description
Summary of within-participant change across treatment arms from the pre-VRC01 time point to the post-VRC01 time point. For Arm A, the pre-VRC01 time point used was the baseline measure (geometric average of screening and entry results) and the post-VRC01 time point was the week 6 measure. For Arm B, the pre-VRC01 time point used was the week 6 measure and the post-VRC01 time point was the week 12 measure. Change in CA-RNA/DNA ratio was calculated on the log10 scale.
Time Frame
Screening, entry and weeks 6 and 12
Title
Cell-associated HIV-1 RNA in Total CD4+ Cells
Description
Testing priority was given to samples from screening, entry and weeks 3, 6, 9 and 12. Baseline values are the geometric mean of screening and entry results. Testing of specimens at weeks 1, 4, 7, 10, 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Cell-associated HIV-1 DNA in Total CD4+ Cells
Description
Testing priority was given to samples from screening, entry and weeks 3, 6, 9 and 12. Baseline values are the geometric mean of screening and entry results. Testing of specimens at weeks 1, 4, 7, 10, 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells
Description
Testing priority was given to samples from screening, entry and weeks 3, 6, 9 and 12. Baseline values are the geometric mean of screening and entry results. Testing of specimens at weeks 1, 4, 7, 10, 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Number of Participants With Plasma HIV-1 RNA by Single Copy Assay (SCA) Below Assay Lower Limit
Description
The analysis of HIV-1 RNA SCA assessed the number of participants below the assay lower limit (1 copy/mL) at each measurement week. Specific specimens and time points were targeted based on Arm. Samples were not tested for Arm A at the Week 7 and Week 10 time points. Samples were not tested for Arm B at the Week 1 and Week 4 time points.
Testing of specimens at weeks 15, 18 and 30 has not been performed. The study team has decided in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
CD4+ T-cell Counts
Description
Baseline measure represents the average of screening and entry results
Time Frame
Measured at screening, entry and weeks 6, 12, 18 and 30
Title
CD8+ T-cell Counts
Description
Baseline measure represents the average of screening and entry results
Time Frame
Measured at screening, entry and weeks 6, 12, 18 and 30
Title
Total/Inducible Virus Recovery - Stimulated HIV-1 RNA
Description
As part of the total virus recovery assay, results for stimulated HIV-1 RNA (copies/mL) are generated
Time Frame
Measured at pre-entry, week 6 and week 12
Title
Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA
Description
As part of the total virus recovery assay, results for unstimulated HIV-1 RNA (copies/mL) are generated
Time Frame
Measured at pre-entry, week 6 and week 12
Title
Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio
Description
As part of the total virus recovery assay, results for stimulated and unstimulated HIV-1 RNA (copies/mL) are generated. At each time point, the ratio of the stimulated to unstimulated HIV-1 RNA was calculated.
Time Frame
Measured at pre-entry, week 6 and week 12
Title
Total/Inducible Virus Recovery - Stimulated Cell Fluor
Description
As part of the total virus recovery assay, results for stimulated cell fluor (light units) are generated.
Time Frame
Measured at pre-entry, week 6 and week 12
Title
Total/Inducible Virus Recovery - Unstimulated Cell Fluor
Description
As part of the total virus recovery assay, results for unstimulated cell fluor (light units) are generated.
Time Frame
Measured at pre-entry, week 6 and week 12
Title
Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio
Description
As part of the total virus recovery assay, results for stimulated and unstimulated cell fluor (light units) are generated. At each time point, the ratio of the stimulated to unstimulated cell fluor was calculated.
Time Frame
Measured at pre-entry, week 6 and week 12
Title
Total/Inducible Virus Recovery - Percentage of Total CD4 Yield
Description
As part of the total virus recovery assay, results for %tCD4 yield are generated.
Time Frame
Measured at pre-entry, week 6 and week 12
Title
Change in Total/Inducible Virus Recovery - Stimulated HIV-1 RNA
Description
As part of the total virus recovery assay, results for stimulated HIV-1 RNA (copies/mL) are generated. The change from the pre-treatment time point to week 6 was assessed as a fold change (week 6 / pre-entry)
Time Frame
Measured at pre-entry, week 6
Title
Change in Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA
Description
As part of the total virus recovery assay, results for unstimulated HIV-1 RNA (copies/mL) are generated. The change from the pre-treatment time point to week 6 was assessed as a fold change (week 6 / pre-entry)
Time Frame
Measured at pre-entry, week 6
Title
Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio
Description
As part of the total virus recovery assay, results for stimulated and unstimulated HIV-1 RNA (copies/mL) are generated. At each time point, the ratio of the stimulated to unstimulated HIV-1 RNA was calculated. The fold change of this ratio from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Time Frame
Measured at pre-entry and week 6
Title
Change in Total/Inducible Virus Recovery - Stimulated Cell Fluor
Description
As part of the total virus recovery assay, results for stimulated cell fluor (light units) are generated. The fold change from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Time Frame
Measured at pre-entry, week 6
Title
Change in Total/Inducible Virus Recovery - Unstimulated Cell Fluor
Description
As part of the total virus recovery assay, results for unstimulated cell fluor (light units) are generated. The fold change from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Time Frame
Measured at pre-entry, week 6
Title
Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio
Description
As part of the total virus recovery assay, results for stimulated and unstimulated cell fluor (light units) are generated. At each time point, the ratio of the stimulated to unstimulated cell fluor was calculated. The fold change of this ratio from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Time Frame
Measured at pre-entry, week 6
Title
Change in Total/Inducible Virus Recovery - Percentage of Total CD4 Yield
Description
As part of the total virus recovery assay, results for %tCD4 yield are generated. The fold change from pre-entry to the week 6 time point was calculated for each arm (week 6 / pre-entry)
Time Frame
Measured at pre-entry, week 6
Title
VRC01 Antibody Level
Description
Summarize the pharmacokinetics (PK) of two infusions of VRC01 during study follow up
Specific specimens and time points were targeted for testing based on Arm. Samples for Arm A were not tested for the Week 6 and Week 9 post-infusion time points. Samples for Arm B were not tested for the Week 0 and Week 3 post-infusion time points.
Time Frame
Measured at entry and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18 and 30
Title
Detectability of Antibody to VRC01 as Measured in Serum
Description
Assess the detectability of antibody to VRC01 in samples collected during study follow-up. Intended to be result from specimen at week 30 time point. Due to specimen availability, four participants in Arm A had results from specimens from the week 18 time point. Counts provided are number of participants with detectable anti-VRC01 antibody result.
Time Frame
Measured at week 30
Title
Levels of T-cell Activation
Description
% CD4+ and CD8+ T-cells co-expressing human leukocyte antigen (HLA)-DR and CD38
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Levels of NK Cell Activation
Description
% NK cells expressing CD69 or CD95
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Plasma Levels of sCD163
Description
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Plasma Levels of sCD14
Description
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Plasma Levels of Interleukin-6 (IL-6)
Description
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Plasma Levels of Human Soluble Tumor Necrosis Factor Alpha-receptor (sTNFαR)
Description
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Plasma Levels of Tumor Necrosis Factor Alpha (TNFα)
Description
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
Plasma Levels of High-sensitivity C-reactive Protein (hsCRP)
Description
Not conducted as part of primary analysis and there are no future plans to assess this outcome. Samples were collected for this outcome in order to assess associations with virologic effects observed. Due to the lack of virologic effect observed, the study team has decided that this outcome is no longer of priority/interest and will be abandoned in favor of saving these samples for future research purposes.
Time Frame
Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Title
VRC01 Antibody Level Relative to Infusion Timing
Description
Summarize the pharmacokinetics (PK) of two infusions of VRC01 during study follow up - aligning the timing of PK samples/results to the respective VRC01 infusions for each Arm
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharon Riddler, MD, MPH
Organizational Affiliation
Pitt CRS
Official's Role
Study Chair
Facility Information:
Facility Name
UCSD Antiviral Research Center CRS
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins University CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital CRS (MGH CRS)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington University Therapeutics (WT) CRS
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1010
Country
United States
Facility Name
University of Rochester Adult HIV Therapeutic Strategies Network CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Chapel Hill CRS
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Ohio State University CRS
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pittsburgh CRS
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt Therapeutics (VT) CRS
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37204
Country
United States
Facility Name
Houston AIDS Research Team CRS
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104-9929
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30364428
Citation
Riddler SA, Zheng L, Durand CM, Ritz J, Koup RA, Ledgerwood J, Bailer RT, Koletar SL, Eron JJ, Keefer MC, Macatangay BJC, Cyktor JC, Mellors JW; AIDS Clinical Trials Group A5342 Protocol Team. Randomized Clinical Trial to Assess the Impact of the Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01 on HIV-1 Persistence in Individuals on Effective ART. Open Forum Infect Dis. 2018 Oct 20;5(10):ofy242. doi: 10.1093/ofid/ofy242. eCollection 2018 Oct.
Results Reference
derived
Links:
URL
http://rsc.tech-res.com/safetyandpharmacovigilance/
Description
To grade diagnoses, signs and symptoms, and laboratory results, sites referred to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014
Learn more about this trial
Evaluating the Safety, Tolerability, and Effect of a Human Monoclonal Antibody (VRC01) on Markers of HIV Persistence in HIV-Infected Adults Receiving Antiretroviral Therapy (ART)
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