VRC-HIVMAB060-00-AB (VRC01) in People With Chronic HIV Infection Undergoing Analytical Treatment Interruption
Condition: HIV
MeSH terms: HIV Infections
Intervention: VRC-HIVMAB060-00-AB (VRC01)
Intervention description: A potent HIV-specific monoclonal antibody
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV Neutralizing Antibodies; HIV Therapy

Summary:

      Background:

      - A combination of daily drugs (called cART) can keep human immunodeficiency virus (HIV) very
      low for a long time. But cART can lose effectiveness and cause permanent side effects. If
      treatment stops, HIV levels go up again. Researchers want to see if a new product can control
      HIV levels when a person is off cART.

      Objective:

      - To see if the new product VRC01 is safe and can control the HIV level in the blood when a
      person is not taking cART.

      Eligibility:

      - Adults ages 18-65 with HIV who are willing to interrupt their treatment for at least 24
      weeks.

      Design:

        -  Participants will be screened with:

        -  Physical exam

        -  Medical history

        -  Heart tests

        -  Blood and urine tests.

        -  Their HIV drugs may be switched. They will keep taking them until a few days after Visit
           1.

        -  Visit 1: Repeat screening procedures.

        -  Participants will also have genetic testing and leukapheresis. For this, blood will be
           removed through a needle in one arm and circulated through a machine that removes white
           blood cells. The rest of the blood is returned through a needle in the other arm.

        -  They will get the first study drug dose through a thin tube in an arm vein for about 1
           hour.

        -  For 24 weeks, participants will have 16 visits. They will have blood drawn every visit.
           At some visits they will repeat the screening procedures and get another VRC01 dose.
           They may have another leukapheresis.

        -  Four weeks after the last dose, participants will restart their cART. For 20 weeks, they
           will have monthly visits to repeat the screening procedures and discuss new symptoms.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

               1. Age 18-65 years old.

               2. HIV-1 infection and clinically stable.

               3. In general good health and with an identified primary health care provider for
                  medical management of HIV infection and willing to maintain a relationship with a
                  primary health care provider for medical management of HIV infection while
                  participating in the study.

               4. CD4+ cell count >450 cells/mm^3 at screening.

               5. Documentation of continuous cART treatment with suppression of plasma viral level
                  below the limit of detection for greater than or equal to 3 years. Subjects with
                  blips (i.e., detectable viral levels on cART) prior to screening may be included
                  provided they satisfy the following criteria:

                    1. The blips are <400 copies/mL, and

                    2. Succeeding viral levels return to levels below the limit of detection on
                       subsequent testing.

               6. Willingness to undergo ATI.

               7. Laboratory values within pre-defined limits at screening:

                    1. Absolute neutrophil count >1,000/mm^3.

                    2. Hemoglobin levels >10.0 g/dL for men and >9.0 g/dL for women.

                    3. Platelet count >100,000/mm^3.

                    4. Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit
                       of normal (ULN).

                    5. Estimated or a measured creatinine clearance rate of greater than or equal
                       to 50 mL/min as determined by the NIH Clinical Center laboratory.

                    6. AST and ALT levels of <2.5 x ULN.

               8. Willingness to have samples stored for future research.

        Reproductive Risks

        Contraception: The effects of VRC01 on the developing human fetus are unknown. For this
        reason, men and women of childbearing potential must agree to use adequate pregnancy
        prevention per the investigator. This includes highly reliable established lifestyle of
        complete abstinence of potentially reproductive sexual activity, or use of BOTH a long term
        hormonal or barrier (e.g. implant, depot injection, IUD in female participant or female
        partner of participant) method of contraception that is fully effective prior to dosing,
        COMBINED WITH a barrier method (male or female condom) for all potentially reproductive
        sexual activity. Pregnancy prevention must be maintained as effective and practiced
        continuously for the duration of study participation. Females of childbearing-age must have
        a negative pregnancy test result prior to receiving VRC01. During the course of the study,
        if a female participant, or the partner of a male participant suspects or in fact becomes
        pregnant, the effected participant should inform the study staff immediately, as well as
        the woman's primary care physician. Subjects must use safe sex practices during the trial,
        and particularly during the ATI phase, when risk of transmission of HIV may be increased.

          -  EXCLUSION CRITERIA

               1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface
                  antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a
                  positive test for HCV RNA. Subjects with a positive test for HCV antibody and a
                  negative test for HCV RNA are eligible.

               2. Documented virologic failure to >1 cART regimen.

               3. HIV immunotherapy or vaccine(s) received within 1 year prior to screening.

               4. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza,
                  pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.

               5. Receipt of other investigational study agent within 28 days of enrollment.

               6. Any active malignancy that may require systemic chemotherapy or radiation
                  therapy.

               7. Systemic immunosuppressive medications received within 3 months prior to
                  enrollment (Not excluded: corticosteroid nasal spray or inhaler; topical
                  corticosteroids for mild, uncomplicated dermatitis; or oral/parenteral
                  corticosteroids administered for non-chronic conditions not expected to recur
                  [length of therapy less than or equal to 10 days, with completion in greater than
                  or equal to 30 days prior to enrollment]).

               8. History or other clinical evidence of:

                    1. Significant or unstable cardiac disease (e.g., angina, congestive heart
                       failure, recent myocardial infarction).

                    2. Severe illness, malignancy, immunodeficiency other than HIV, or any other
                       condition that, in the opinion of the investigator, would make the subject
                       unsuitable for the study.

               9. Active drug or alcohol use or any other pattern of behavior that, in the opinion
                  of the investigator, would interfere with adherence to study requirements.

              10. Breast-feeding.