Dose, Safety, Tolerability, and Immunogenicity of an HIV-1 Vaccine, VRC-HIVRGP096-00-VP, With Alum in Healthy Adults
Condition: Human Immunodeficiency Virus Prevention; Human Immunodeficiency Virus (HIV)
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      HIV stands for human immunodeficiency virus, which is the virus that causes AIDS. There is
      currently no licensed vaccine to prevent HIV infection. Researchers want to test a vaccine
      called Trimer 4571 for the first time. It was made at the National Institutes of Health (NIH)
      and contains no HIV. The vaccine is mixed with a substance called alum and injected in the
      arm. Alum is included to boost the body's immune response to the vaccine. It has been used in
      licensed vaccines for over 60 years and has been found to be safe.

      Objectives:

      To see if the vaccine Trimer 4571 is safe, well-tolerated, and to study immune responses to
      it.

      Eligibility:

      Healthy adults ages 18-50 years

      Design:

      Participants were screened with a physical exam and blood tests. They agreed to not become
      pregnant and to avoid behavior that would put them at high-risk for HIV infection during the
      study.

      Participants had about 15 study visits over about 9 months.

      The first 6 participants received a low dose of the vaccine mixed with alum.

      Once the low dose was deemed safe, 10 new participants were allocated to receive a higher
      dose.

      All participants were randomly assigned to get the vaccine by injection in a muscle or under
      the skin.

      All participants received a total of 3 vaccine injections over 20 weeks. Each visit where
      participants received the vaccine lasted about 5 hours. Participants were watched after each
      injection. Participants who were able to get pregnant would have a pregnancy test before each
      injection.

      Participants received a thermometer and recorded their temperature and symptoms every day for
      1 week after each injection. The injection site was checked for redness, swelling, or
      bruising.

      At follow-up visits, participants had blood drawn and checked for health changes or problems.
      Follow up visits lasted about 1-2 hours.
    

Detailed description: 
      Design:

      This is a Phase I, open-label, dose escalation study to evaluate the dose, safety,
      tolerability, and immunogenicity of VRC-HIVRGP096-00-VP (Trimer 4571) with aluminum hydroxide
      suspension (alum) as adjuvant in a three-injection regimen. The hypotheses were that the
      vaccine will be safe and tolerable and will induce detectable immune responses. The primary
      objective was to evaluate the safety and tolerability of the investigational vaccine at three
      doses administered with alum. Secondary objectives were to evaluate humoral and cellular
      immunogenicity of the investigational vaccine regimens.

      Study Product:

      VRC-HIVRGP096-00-VP (Trimer 4571) was developed by the Vaccine Research Center (VRC),
      National Institute of Allergy and Infectious Diseases (NIAID). The soluble HIV-1 envelope
      product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain
      BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by
      broadly neutralizing antibodies and resists gp120 conformational change caused by CD4
      binding. Injections were administered intramuscularly (IM) and subcutaneously (SC) in a 1 mL
      volume by needle and syringe. The product was provided at a 500 mcg/mL concentration in 3 mL
      glass vials filled to 1.2 +/- 0.10 mL. Adjuvant is an aluminum hydroxide suspension (alum)
      provided in a sterile, pyrogen-free suspension at a concentration of 5 mg/mL in 3 mL glass
      vials filled to 0.7 +/- 0.10 mL.

      Participants:

      Healthy adults ages 18 to 50.

      Study Plan:

      Participants received VRC-HIVRGP096-00-VP at doses of 100 mcg or 500 mcg, both with 500 mcg
      alum field mixed, administered via IM or SC injections. A dose escalation evaluation occurred
      to ensure the safety data supported proceeding to the higher dose. Participants were
      evaluated for safety and immune responses through blood collection at specified timepoints
      throughout the study.

      The study schema is below:

      --------------------

      Group 1: Participants = 3; Route = IM; Dose (mcg) = 100; Day** 0, Week** 8, Week** 20

      Group 2: Participants = 3; Route = SC; Dose (mcg) = 100; Day** 0, Week** 8, Week** 20

      Group 3: Participants = 5; Route = IM; Dose (mcg) = 500; Day** 0, Week** 8, Week** 20

      Group 4: Participants = 5; Route = SC; Dose (mcg) = 500; Day** 0, Week** 8, Week** 20

      Total = 16 Participants

      **500 mcg of alum was mixed with Trimer 4571 for all groups

      Duration:

      Participants were followed for 40 weeks.
    

Intervention name(s): VRC-HIVRGP096-00-VP; Alum Adjuvant
Intervention type(s): Biological; Other
Intervention description(s): Trimer 4571 drug product is an investigational HIV vaccine which mimics the native HIV-1 envelope complex. This soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding.; Adjuvant is an aluminum hydroxide suspension (alum) mixed with Trimer 4571 to improve the immune response to the investigational vaccine.
Other intervention name(s): Trimer 4571; Aluminum Hydroxide Suspension; Alum
Intervention MeSH terms: Aluminum Hydroxide; Aluminum sulfate
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Human Immunodeficiency Virus; Immune Response; Neutralizing Antibodies; HIV Prevention; Cellular Immunogenicity