Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: VRC01
Intervention description: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP.
Administered over about 30 to 60 minutes using a volumetric pump.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK),
      and antiviral activity of an antibody (called VRC01) in HIV-infected adults whose HIV was
      well-controlled with HIV medicines. The study examined whether VRC01 controlled or delayed
      the return of HIV viremia when the participants' HIV medicines were briefly stopped during
      the study.
    

Eligibility criteria:

        Step 1 Inclusion Criteria:

          -  HIV-1 infection, documented by any licensed 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 and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load
             (VL). More information on this criterion can be found in the protocol.

          -  Ability and willingness of participant or legal representative to provide informed
             consent

          -  Clinically stable on their first or second ART regimen that includes a boosted
             protease inhibitor or an integrase inhibitor. The current regimen should have been
             stable for 8 weeks at the time of entry. Changes while the patient HIV viral load was
             undetectable did not count toward the number of ART regimens used, (for example, an
             individual switching from a non-nucleoside reverse transcriptase inhibitor
             (NNRTI)-based regimen to an integrase inhibitor based regimen while the HIV viral load
             is undetectable would still be on their first regimen).

          -  HIV-1 RNA that is less than 50 copies/mL using a Food and Drug Administration
             (FDA)-approved assay performed by any laboratory that has a Clinical Laboratory
             Improvement Amendments (CLIA) certification or its equivalent within 45 days prior to
             study entry

          -  HIV-1 RNA less than 50 copies/mL using a FDA-approved assay for at least 24 weeks
             prior to study entry performed by any laboratory that had a CLIA certification or its
             equivalent. More information on this criterion can be found in the protocol.

          -  Screening CD4+ T-cell count greater than or equal to 450 cells/μL within 45 days prior
             to study entry

          -  Nadir CD4+ T-cell count greater than 200 cells/μL

          -  Willingness to have blood samples collected, stored indefinitely, and used for
             study-related research purposes

          -  The following laboratory values obtained within 45 days prior to enrollment:

               -  Absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm^3

               -  Hemoglobin greater than or equal to 12.0 g/dL for men and greater than or equal
                  to 11.0 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. More information on this criterion can be found in the
                  protocol.

               -  Alanine aminotransferase (ALT) less than or equal to 2.0 times the upper limit of
                  normal (ULN)

          -  At least eight participants had availability of plasma or serum specimen before the
             initiation of ART either in the Center for AIDS Research (CFAR) repository of the
             University of Pennsylvania, University of Alabama, or in the AIDS Clinical Trials
             Group (ACTG) central repository

          -  For females of reproductive potential (i.e., women who have not been post-menopausal
             for at least 24 consecutive months; who had menses within the preceding 24 months; or
             women who had not undergone surgical sterilization, specifically hysterectomy and/or
             bilateral oophorectomy or bilateral salpingectomy), negative urine pregnancy test
             (with a sensitivity of 15 to 25 mIU/mL) within 48 hours prior to screening and entry.
             More information on this criterion can be found in the protocol.

          -  Contraceptive methods were required for female participants of reproductive potential.
             Female participants of reproductive potential and their male partners MUST HAVE
             appropriately used at least two contraceptives, with one method being highly effective
             and the other method being either highly effective or less effective. More information
             on this criterion, including a list of acceptable contraceptive options, can be found
             in the protocol.

          -  Contraceptive methods were required for female partners of reproductive potential of
             male study participants on study drug. Female partners of reproductive potential of
             male study participants and/or their male partners MUST HAVE appropriately used at
             least two contraceptives, with one method being highly effective and the other method
             being either highly effective or less effective. More information on this criterion,
             including a list of acceptable contraceptive options, can be found in the protocol.

          -  Negative hepatitis B surface antigen (HBsAg) result obtained within 6 months prior to
             study entry

          -  Hepatitis C virus (HCV) antibody negative result within 6 months prior to entry, or if
             the HCV antibody result was positive, a negative HCV RNA obtained within 6 months
             prior to study entry

          -  Adequate venous access in at least one arm

        Step 2 Inclusion Criteria:

          -  Entry into Step 1 of this study (A5340)

          -  Receipt of at least one dose or partial dose of VRC01 in Step 1

          -  Reinitiating ART for protocol or non-protocol-defined reasons. More information on
             this criterion can be found in the protocol.

        Step 3 Inclusion Criteria:

          -  Entry into and completion of Step 2 of this study (A5340) at least 3 months prior

          -  HIV-1 RNA less than 50 copies/ml at pre-entry visit

          -  Ability and willingness of participant or legal representative to provide informed
             consent

          -  Willingness to have blood samples/specimens collected, stored indefinitely, and used
             for study-related research purposes

          -  Adequate venous access in at least one arm

        Step 1 Exclusion Criteria:

          -  Previous receipt of humanized or human monoclonal antibody whether licensed or
             investigational

          -  Weight greater than 115 kg or less than 53 kg

          -  History of an AIDS-defining illness

          -  Ongoing AIDS-related opportunistic infection (including oral thrush)

          -  History of a severe allergic reaction with generalized urticaria, angioedema, or
             anaphylaxis in the 2 years prior to enrollment

          -  Currently breastfeeding

          -  Receipt of other investigational study agent within 30 days prior to enrollment

          -  Treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or
             other immunomodulators (other than nonsteroidal anti-inflammatory drugs [NSAIDs])
             within 30 days prior to enrollment

          -  Any other chronic or clinically significant medical condition that in the opinion of
             investigator would have jeopardized the safety or rights of the participant,
             including, but not limited to diabetes mellitus type I, OR clinically significant
             forms of drug or alcohol abuse, severe asthma, autoimmune disease, uncontrolled
             hypertension, liver disease, psychiatric disorders, heart disease, or cancer

          -  Treatment during acute infection (i.e., treatment within 6 months of acute infection)

          -  Current use of a NNRTI

        Step 2 Exclusion Criteria:

          -  Non-participation in Step 1

        Step 3 Exclusion Criterion:

          -  Non-participation in Step 2