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)
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: VRC01; Placebo
Intervention description: 40 mg/kg of VRC01 administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump; Normal saline administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV; VRC01

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).
    

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)