Safety and Tolerability of AAV8 Delivery of a Broadly Neutralizing Antibody in Adults Living With HIV: a Phase 1, Dose-escalation Trial
Condition: HIV-1 Infected Adults With Controlled Viremia
MeSH terms: Viremia
Intervention: VRC-HIVAAV070-00-GT (AAV8-VRC07)
Intervention description: AAV8-VRC07 is a recombinant AAV vector expressing a HIV-1 CD4 binding site-specific neutralizing antibody, VRC07
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: ARV Therapy; Broadly Neutralizing; Gene Transfer; Monoclonal Antibody; AAV8

Summary:

      Background:

      The Human Immunodeficiency Virus (HIV) attacks the immune system. Scientists have created a
      gene that could be transferred to the cells of people with HIV. The gene should tell the
      cells to make an antibody called VRC07. This antibody fights HIV. The VRC07 gene is packaged
      into a man-made version of a virus called AAV8.

      Objectives:

      To see if AAV8-VRC07 is safe. To study if it causes cells to produce the VRC07 antibody.

      Eligibility:

      Adults ages 18-65 who are HIV infected but in general good health and have been taking the
      same HIV medicine for at least 3 months

      Design:

      Participants were screened in a different protocol.

      Participants received the study product on day 1. It was injected one or more times in the
      upper arm or thigh using a needle. Participants weight was measured to calculate the dose.

      Women may have had a pregnancy test.

      For 7 days after getting the study product, participants checked their temperature with a
      thermometer. They noted any symptoms in an electronic or paper diary.

      Participants will have study visits. At each one, they will have a physical exam and medical
      history. They will have blood drawn and may have saliva collected.

      The study visit schedule is as follows:

      For 12 weeks: 1 visit a week

      For the next 12 weeks: 1 visit every other week

      Then about 1 visit a month

      After 1 year in the study: a visit every 6 months for the next 4 years.

      Total study participation is 5 years.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        A volunteer must have met all of the following criteria:

          -  Able and willing to complete the informed consent process.

          -  18 to 65 years of age.

          -  HIV-1 infected.

          -  On a stable antiretroviral regimen for greater than or equal to 3 months.

          -  Available for clinical follow-up through the last study visit.

          -  Based on history and examination, must be in general good health with no evidence of
             clinically significant lab abnormalities and without additional clinically significant
             medical conditions as per exclusion criteria.

          -  Willing to maintain or establish a relationship with a primary health care provider
             for medical management of HIV infection while participating in the study.

          -  Willing to have blood samples collected, stored indefinitely, and used for research
             purposes.

          -  Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process.

          -  Laboratory tests assessing individual's health will be conducted within 84 days prior
             to enrollment and values must meet the following criteria:

               1. White blood cell count (WBC) 2,500-12,000/mm^3;

               2. WBC differential either within institutional normal range or accompanied by
                  approval of the Principal Investigator (PI) or designee;

               3. Platelets = 125,000-400,000/mm^3;

               4. Hemoglobin greater than or equal to 10.0 gm/dL;

               5. Creatinine less than or equal to 1.25 x upper limit of normal (ULN);

               6. Alanine aminotransferase (ALT) less than or equal to 1.1 x ULN;

               7. Aspartate aminotransferase (AST) less than or equal to 1.1 x ULN; and,

               8. Viral Load (VL) less than or equal to 50 copies/mL and a CD4 count greater than
                  or equal to 300/mcL (microliter).

                  Male-Specific Criteria:

          -  Males must agree to use condoms for all sexual activity of any reproductive potential
             for 52 weeks after receiving the study product.

        Female-Specific Criteria:

          -  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 through
             study Week 52, or to be monogamous with a partner who has had a vasectomy.

          -  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 volunteer would have been excluded if one or more of the following conditions applied:

          -  Previous receipt of monoclonal antibody whether licensed or investigational.

          -  Previous receipt of gene therapy product.

          -  Ongoing AIDS-related opportunistic infection (including oral thrush).

          -  Active injection drug use or active drug or alcohol use or dependence that, in the
             opinion of the site investigator, would interfere with adherence to study
             requirements.

          -  A titer of pre-existing antibodies to AAV8 capsid is greater than 1:90.

          -  Weight > 115 kg for Group 3 participants only.

          -  History of a severe allergic reaction with generalized urticaria, angioedema or
             anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of
             recurrence.

          -  Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions) or significant bruising or bleeding
             difficulties with IM injections or blood draws.

          -  Active liver disease such as chronic hepatitis.

          -  Hypertension that is not well controlled by medication.

          -  Woman who is breast-feeding or planning to become pregnant during the study
             participation.

          -  Receipt of any investigational study agent within 28 days prior to enrollment.

          -  Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

          -  Any other chronic or clinically significant medical condition that in the opinion of
             investigator would jeopardize the safety or rights of the volunteer, including, but
             not limited to: diabetes mellitus type I; OR clinically significant forms of asthma,
             autoimmune disease, psychiatric disorders, heart disease, or cancer.