HIV InfectionsPhase 1NCT02411539
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)
A Phase 1 study testing VRC01 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- VRC01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 13 sitesUnited States
- Study dates
- 25 Aug 2015to 29 Sep 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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
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- 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)
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80045
Johns Hopkins University CRS
Baltimore, Maryland, 21205
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, 02114
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Northwestern University CRS
Chicago, Illinois, 60611
Ohio State University CRS
Columbus, Ohio, 43210
Houston AIDS Research Team CRS
Houston, Texas, 77030
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, 37204
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, 15213
University of Rochester Adult HIV Therapeutic Strategies Network CRS
Rochester, New York, 14642
UCSD Antiviral Research Center CRS
San Diego, California, 92103
University of Washington AIDS CRS
Seattle, Washington, 98104-9929
Washington University Therapeutics (WT) CRS
St Louis, Missouri, 63110-1010
About this study
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
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).
Read the 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.
- Conditions
- HIV Infections
- Being tested
- VRC01, Placebo
- Keywords
- HIV, VRC01
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VRC01Biological
Also called VRC-HIVMAB060-00-AB
40 mg/kg of VRC01 administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
PlaceboBiological
Normal saline administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
| Study group | Role | What they receive |
|---|---|---|
| Arm A: VRC01 followed by placebo | Experimental | Participants received an infusion of VRC01 at Day 0 and Week 3 and an infusion of placebo (normal saline) at Weeks 6 and 9. Receives: Biological: VRC01; Biological: Placebo |
| Arm B: placebo followed by VRC01 | Experimental | Participants received an infusion of placebo (normal saline) at Day 0 and Week 3 and an infusion of VRC01 at Weeks 6 and 9. Receives: Biological: VRC01; Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Measured from study treatment initiation to study discontinuation (study duration is 30 weeks)
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
Measured: Screening, entry and week 6
Secondary outcomes (34)
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
Measured: 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)
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.
Measured: Screening, entry, week 3 and week 6 (week 3 used as LVCF if necessary)
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.
Measured: Screening, entry and weeks 6 and 12
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.
Measured: 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
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.
Measured: Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
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.
Measured: Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
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.
Measured: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
CD4+ T-cell Counts
Baseline measure represents the average of screening and entry results
Measured: Measured at screening, entry and weeks 6, 12, 18 and 30
CD8+ T-cell Counts
Baseline measure represents the average of screening and entry results
Measured: Measured at screening, entry and weeks 6, 12, 18 and 30
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
Measured: Measured at pre-entry, week 6 and week 12
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
Measured: Measured at pre-entry, week 6 and week 12
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.
Measured: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Stimulated Cell Fluor
As part of the total virus recovery assay, results for stimulated cell fluor (light units) are generated.
Measured: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Unstimulated Cell Fluor
As part of the total virus recovery assay, results for unstimulated cell fluor (light units) are generated.
Measured: Measured at pre-entry, week 6 and week 12
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.
Measured: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Percentage of Total CD4 Yield
As part of the total virus recovery assay, results for %tCD4 yield are generated.
Measured: Measured at pre-entry, week 6 and week 12
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)
Measured: Measured at pre-entry, week 6
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)
Measured: Measured at pre-entry, week 6
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)
Measured: Measured at pre-entry and week 6
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)
Measured: Measured at pre-entry, week 6
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)
Measured: Measured at pre-entry, week 6
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)
Measured: Measured at pre-entry, week 6
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)
Measured: Measured at pre-entry, week 6
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.
Measured: 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
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.
Measured: Measured at week 30
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.
Measured: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
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.
Measured: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
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.
Measured: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
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.
Measured: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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
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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2015 (estimated)
- Study start25 Aug 2015
- Primary completion15 Apr 2016
- Study completion29 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Responsible party
- Sponsor
- Investigators
- Sharon Riddler, MD, MPH, Study chair, Pitt CRS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02411539
- Sponsor's protocol ID
- ACTG A5342
- Other IDs
- 12003, UM1AI068636
- Status last verified
- Jun 2018
- First submitted
- 2 Apr 2015
- Last updated
- 5 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30364428
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02411539
- Acronym / sponsor ID
- ACTG A5342
- Conditions
- HIV Infections
- Keywords
- HIV, VRC01
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Study start
- 25 Aug 2015 (actual)
- Primary completion
- 15 Apr 2016 (actual)
- Study completion
- 29 Sep 2016 (actual)
- First posted
- 8 Apr 2015 (estimated)
- Results
- Posted 31 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: VRC01 followed by placebo | Experimental | Biological: VRC01, Biological: PlaceboParticipants received an infusion of VRC01 at Day 0 and Week 3 and an infusion of placebo (normal saline) at Weeks 6 and 9. |
| Arm B: placebo followed by VRC01 | Experimental | Biological: VRC01, Biological: PlaceboParticipants received an infusion of placebo (normal saline) at Day 0 and Week 3 and an infusion of VRC01 at Weeks 6 and 9. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VRC01Also: VRC-HIVMAB060-00-AB40 mg/kg of VRC01 administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump | Biological | Arm A: VRC01 followed by placebo, Arm B: placebo followed by VRC01 |
| PlaceboNormal saline administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump | Biological | Arm A: VRC01 followed by placebo, Arm B: placebo followed by VRC01 |
Primary outcome
Number of Participants Who Experienced Grade 3 or Greater, Treatment Related, Adverse Event (AE)
Time frame: 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
Time frame: 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
34 secondary outcomes
Number of Participants With Premature Treatment Discontinuation, for Reasons Related to Study Treatment
Time frame: 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)
Time frame: Screening, entry, week 3 and week 6 (week 3 used as LVCF if necessary)
Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Across Arms
Time frame: Screening, entry and weeks 6 and 12
Cell-associated HIV-1 RNA in Total CD4+ Cells
Time frame: 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
Time frame: Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells
Time frame: Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Number of Participants With Plasma HIV-1 RNA by Single Copy Assay (SCA) Below Assay Lower Limit
Time frame: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
CD4+ T-cell Counts
Time frame: Measured at screening, entry and weeks 6, 12, 18 and 30
CD8+ T-cell Counts
Time frame: Measured at screening, entry and weeks 6, 12, 18 and 30
Total/Inducible Virus Recovery - Stimulated HIV-1 RNA
Time frame: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA
Time frame: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio
Time frame: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Stimulated Cell Fluor
Time frame: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Unstimulated Cell Fluor
Time frame: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio
Time frame: Measured at pre-entry, week 6 and week 12
Total/Inducible Virus Recovery - Percentage of Total CD4 Yield
Time frame: Measured at pre-entry, week 6 and week 12
Change in Total/Inducible Virus Recovery - Stimulated HIV-1 RNA
Time frame: Measured at pre-entry, week 6
Change in Total/Inducible Virus Recovery - Unstimulated HIV-1 RNA
Time frame: Measured at pre-entry, week 6
Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated HIV-1 RNA Ratio
Time frame: Measured at pre-entry and week 6
Change in Total/Inducible Virus Recovery - Stimulated Cell Fluor
Time frame: Measured at pre-entry, week 6
Change in Total/Inducible Virus Recovery - Unstimulated Cell Fluor
Time frame: Measured at pre-entry, week 6
Change in Total/Inducible Virus Recovery - Stimulated to Unstimulated Cell Fluor Ratio
Time frame: Measured at pre-entry, week 6
Change in Total/Inducible Virus Recovery - Percentage of Total CD4 Yield
Time frame: Measured at pre-entry, week 6
VRC01 Antibody Level
Time frame: 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
Time frame: Measured at week 30
Levels of T-cell Activation
Time frame: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Levels of NK Cell Activation
Time frame: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Plasma Levels of sCD163
Time frame: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Plasma Levels of sCD14
Time frame: Measured at screening, entry and weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30
Plasma Levels of Interleukin-6 (IL-6)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30364428Riddler 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.
- 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 2014Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharon Riddler, MD, MPH study chair
Pitt CRS
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VRC01 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Grade 3 or Greater, Treatment Related, Adverse Event (AE) (time frame: Measured from study treatment initiation to study discontinuation (study duration is 30 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02411539, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.