Dose, Safety, Tolerability and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine in Healthy Adults
Condition: Influenza Infection
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      The flu is a common viral infection that can be deadly for certain people. Vaccines against
      flu have been developed to teach the body to prevent or fight the infection. A new vaccine
      may help the body to make an immune response to H1 flu, a flu strain that infects humans.

      Objective:

      To test the safety and effectiveness of the H1 Stabilized Stem Ferritin vaccine
      (VRC-FLUNPF099-00-VP).

      Eligibility:

      Healthy people ages 18-70 years old who got at least 1 licensed flu vaccine since January 1,
      2014.

      Design:

      Participants received 1 or 2 vaccinations by injections (shots) in the upper arm muscle over
      4 months. Participants received a thermometer and recorded their temperature and symptoms
      every day a diary card for 7 days after each injection. The injection site was checked for
      redness, swelling, or bruising.

      Participants had 9-11 follow-up visits over 12-15 months. At follow-up visits, participants
      had blood drawn and were checked for health changes or problems. Participants who reported
      influenza-like illness had nose and throat swabs for evaluation of viral infection.

      Some participants had apheresis. A needle was placed into a vein in both arms. Blood was
      removed through a needle in the vein of one arm. A machine removed the white blood cells and
      then the rest of the blood was returned to the participant through a needle in the other arm.

      A separate consent was provided to participants for genetic testing on their samples.
    

Detailed description: 
      Study Design: This was a Phase I, open-label, dose escalation study to evaluate the dose,
      safety, tolerability, and immunogenicity of VRC-FLUNPF099-00-VP in two regimens. The
      hypotheses were that the vaccine is safe and tolerable and will elicit an immune response.
      The primary objective was to evaluate the safety and tolerability of the investigational
      vaccine in healthy adults. Secondary objectives were related to immunogenicity of the
      investigational vaccine and dosing regimen.

      Study Products: The investigational vaccine, VRC-FLUNPF099-00-VP (H1ssF_3928), was developed
      by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases
      (NIAID) and is composed of Helicobacter pylori non-heme ferritin assembled with influenza
      virus H1 haemagglutinin (HA) insert to form a nanoparticle displaying eight HA stabilized
      stem trimers from A/New Caledonia/20/1999 (H1N1) influenza. The vaccine was supplied in
      single-use vials at a concentration of 180 mcg/mL. H1ssF_3928 was administered
      intramuscularly (IM) in the deltoid muscle via needle and syringe.

      Participants: Healthy adults between the ages of 18-70 years, inclusive.

      Study Plan: The study evaluated the safety, tolerability and immunogenicity of 1 or 2 doses
      of the H1ssF_3928 vaccine in a dose-escalation design. In Group 1, five participants received
      a single low dose (20 mcg) of H1ssF_3928 on Day 0. For Group 1, the protocol required 1
      vaccination visit, about 9 follow-up visits, and a telephone contact after vaccination.

      Once the low dose was assessed as safe and well tolerated, enrollment began for Group 2A.
      Groups 2A, 2B, 2C, and 2D were stratified by age as shown in the vaccination schema below. In
      Group 2A, participants received a higher dose (60 mcg) of H1ssF_3928 on Day 0. Once this
      higher dose was assessed as safe and well tolerated, participants in Group 2A received a
      second vaccination at Week 16 and enrollment began for Groups 2B, 2C, and 2D. For Groups 2A,
      2B, 2C, and 2D, the protocol required 2 vaccination visits, about 11 follow-up visits, and a
      telephone contact after each vaccination. Group 2A completed the product administration
      schedule per protocol. While most participants in Groups 2B-2D completed the second dose
      administration per protocol, one participant was not able to receive the second dose due to
      moving out of the area and 11 participants were not able to receive their second dose due to
      the COVID-19 pandemic.

      For all groups, solicited reactogenicity was evaluated using a 7-day diary card. Assessment
      of vaccine safety included clinical observation and monitoring of hematological and chemical
      parameters at clinical visits throughout the study.

      VRC 321 Vaccination Schema:

      Group: 1; Age Cohort: 18-40; Participants: 5; Day 0: 20 mcg

      Group: 2A; Age Cohort: 18-40; Participants: 12; Day 0: 60 mcg; Week 16: 60 mcg

      Group: 2B; Age Cohort: 41-49; Participants: 12; Day 0: 60 mcg; Week 16: 60 mcg

      Group: 2C; Age Cohort: 50-59; Participants: 12; Day 0: 60 mcg; Week 16: 60 mcg

      Group: 2D; Age Cohort: 60-70; Participants: 11*; Day 0: 60 mcg; Week 16: 60 mcg

      Total: 52*

      *Recruitment for the final open group, Group 2D, was ongoing to meet the accrual target of 53
      participants. However, due to the COVID-19 pandemic, enrollment was discontinued with a total
      of 52 participants enrolled.

      Study Duration:

      Group 1: Participants were evaluated for 52 weeks following the vaccine administration and
      through an influenza season.

      Groups 2A, 2B, 2C, 2D: Participants were evaluated for 52 weeks following the last vaccine
      administration and through an influenza season.
    

Intervention name(s): VRC-FLUNPF099-00-VP (H1ssF_3928)
Intervention type(s): Biological
Intervention description(s): The vaccine is composed of the HA stem domain from Influenza A/New Caledonia/20/1999 (H1N1) genetically fused to the ferritin protein from H. pylori. Purified H1ssF_3928 particles display eight well-formed HA trimers that antigenically resemble the native H1 stem viral spikes.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Flu; Seasonal Allergy; Respiratory Illness; Flu Virus; Viral Infection