Phase 1, Open-label, Single Dose Study to Examine Safety, Tolerability, Pharmacokinetics and Virologic Impact of VRC01LS or VRC07-523LS in HIV-infected Viremic Adults
Condition: HIV-1
Intervention: VRC-HIVMAB080-00-AB; VRC-HIVMAB075-00-AB
Intervention description: VRC01LS is an investigational human monoclonal antibody targeted to the CD4+ binding site of HIV-1.; VRC07-523LS is an investigational human monoclonal antibody targeted to the CD4+ binding site of HIV-1.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: HIV Viral Load; Antiviral; CD4 Count; HIV-1 Infection; Broadly Neutralizing Antibody

Summary:

      Background:

      The human body uses antibodies as one way to help fight infection. VRC01LS and VRC07-523LS
      are antibodies directed against the HIV virus. Researchers want to see if they are safe and
      well tolerated. In Part A of the study, the researchers studied VRC01LS. Part A of the study
      was completed in 2017. In Part B, the researchers studied VRC07-523LS. Depending on which
      antibody received, researchers studied the amount of VRC01LS or VRC07-523LS in the body and
      how it changes over time. They evaluated the effect of antibodies on CD4+ (Cluster of
      Differentiation 4) lymphocyte count and HIV viral load, and checked to see if people who get
      VRC01LS or VRC07-523LS develop an immune response to it.

      Objective:

      To see if VRC01LS and VRC07-523LS are safe and well tolerated.

      Eligibility:

      Adults ages 18-70 who are HIV infected but otherwise healthy.

      Design:

      Participants received the study drug one time by IV infusion. A needle guided a thin tube
      into a vein. The study drug mixed with salt water was dripped into the vein over about 30
      minutes.

      Participants were monitored for 30 minutes after the infusion.

      Blood samples were taken at the following times:

        -  Once before the infusion

        -  5 times in the 4 hours after the infusion

        -  1 time 24 hours after infusion. Some participants may have had 3 optional blood draws in
           the time period between 4 and 24 hours.

      For 3 days after the infusion, participants recorded their temperature and reactogenicity
      symptoms in a diary.

      There were a total of 23 study visits over 48 weeks. Ten visits were in the first 4 weeks. At
      all visits, participants answered health questions and gave blood samples.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        A participant must meet all of the following criteria:

          1. Able and willing to complete the informed consent process.

          2. 18-70 years old

          3. Available for clinic visits for 48 weeks after study product administration.

          4. HIV-1 infected and clinically stable. [Note: Documented HIV-1 infection by HIV enzyme
             immunoassay (EIA) performed by a Clinical Laboratory Improvement Amendments (CLIA)
             certified outside lab within 28 days of enrollment is acceptable.]

          5. At least one plasma viral load >=500 copies/mL within 28 days of enrollment. A plasma
             viral load within 28 days and closest to the day of enrollment, that is detectable but
             not greater than 100,000 copies/mL. [Note: outside laboratory results will be
             acceptable].

          6. A CD4+ count >=350 cells/microliter (mcL) on 2 of 3 consecutive testing occasions (or
             on 2 of 2 sequential tests) within 28 days prior to enrollment. [Note: outside
             laboratory results will be acceptable].

          7. In general good health as assessed by a study clinician and under the care of a
             primary health care provider for medical management of HIV infection while
             participating in the study. Willing to give consent to contact and send laboratory
             results to the participant's primary health provider.

          8. Willing to have blood samples collected, stored indefinitely, and used for various
             research purposes.

          9. Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process.

         10. Screening laboratory values within 28 days prior to enrollment must meet the following
             criteria:

               -  Absolute neutrophil count >=800/mcL

               -  Platelets >=100,000/mcL

               -  Hemoglobin >=10.0 g/dL

               -  Creatinine less than or equal to 1.31 mg/dL

               -  Alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal
                  (ULN)

               -  Negative Hepatitis B Surface Antigen (HBsAg)

               -  Undetectable Hepatitis C Viral Load (HCV RNA)

             [Note: Documented negative HBsAg and HCV RNA performed by an outside CLIA certified
             lab within 28 days of enrollment are acceptable.]

             Female-Specific Criteria:

         11. If a woman is sexually active with a male partner and has no history of hysterectomy,
             tubal ligation, or menopause, she must agree to use either a prescription birth
             control method or a barrier birth control method from the time of study enrollment
             until the last study visit, or have a monogamous partner who has had a vasectomy.

         12. Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on
             day of enrollment for women presumed to be of reproductive potential.

        EXCLUSION CRITERIA:

        A participant will be excluded if one or more of the following conditions apply:

          1. Previous receipt of humanized or human monoclonal antibody whether licensed or
             investigational.

          2. Prior use of antiretroviral therapy.

          3. Ongoing AIDS-related opportunistic infection (including oral thrush).

          4. Active drug or alcohol use or dependence in the opinion of the site investigator that
             would interfere with adherence to study requirements.

          5. Any history of a severe allergic reaction, including generalized urticaria, angioedema
             or anaphylaxis prior to enrollment, that has a reasonable risk of recurrence during
             the study.

          6. Physical finding on examination considered clinically significant.

          7. Hypertension that is not well controlled.

          8. Weight >115 kg (253 pounds).

          9. Breast-feeding.

         10. Receipt of any investigational study product within 28 days prior to enrollment.

         11. Any other chronic or clinically significant medical condition that in the opinion of
             the investigator would jeopardize the safety or rights of the volunteer.