First-in-Human Clinical Trial of a Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV, in Healthy Adults
Condition: Influenza; Seasonal Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Influenza (flu) is a contagious respiratory illness. It is caused by influenza viruses that
      infect the nose, throat, and sometimes the lungs. Vaccines are given to teach the body to
      prevent or fight infection. Researchers want to study a new vaccine to prevent the seasonal
      flu.

      Objective:

      To see if the FluMos-v1 vaccine is safe and how the body responds to it.

      Eligibility:

      Healthy adults ages 18-50 who received at least one licensed flu vaccine from 2016 through
      the 2019-2020 influenza season.

      Design:

      Participants will be screened through a separate protocol.

      Participants will be tested for COVID-19. They may have a pregnancy test.

      Participants will receive the FluMos-v1 vaccine or the Flucelvax vaccine. It will be injected
      in the upper arm.

      Participants will complete a diary card for 7 days. They will record any symptoms they have.
      They will be given a thermometer to check their temperature. They will also be given a ruler
      to measure any skin changes at the injection site.

      Participants will have about 10 study visits. They will be asked how they are feeling and if
      they have taken any medications. They will have blood drawn.

      Participants will have oral mucosal samples collected using a thin swab. They may have nose
      and throat secretions collected using a thin swab.

      Some participants will have optional apheresis. Blood will be removed through a needle in a
      vein in one arm. A machine will separate the white blood cells. The rest of the blood will be
      returned through a needle in a vein in the other arm.

      Participation will last for 40 weeks.
    

Detailed description: 
      Design:

      This is a Phase I, open-label, dose escalation study to evaluate the dose, safety,
      tolerability, and immunogenicity of the mosaic quadrivalent influenza vaccine
      VRC-FLUMOS0111-00-VP (FluMos-v1). The hypotheses are that the FluMos-v1 vaccine is safe and
      tolerable and will elicit an immune response. The primary objective is to evaluate the safety
      and tolerability of the investigational vaccine alone or with adjuvant in healthy adults.
      Secondary objectives relate to immunogenicity of the investigational vaccine and dosing
      regimen compared with the licensed inactivated seasonal Flucelvax (Registered Trademark)
      quadrivalent influenza vaccine (QIV) in healthy adults.

      Study Products:

      The investigational vaccine FluMos-v1 was developed by the Vaccine Research Center (VRC),
      National Institute of Allergy and Infectious Diseases (NIAID) and is composed of the
      following 4 influenza strains: Influenza A (H1: A/Idaho/07/2018 and H3: A/Perth/1008/2019)
      and Influenza B (Victoria lineage: B/Colorado/06/2017 and Yamagata lineage:
      B/Phuket/3073/2013. FluMos-v1 is supplied in a single-use vial at a concentration of 180
      mcg/mL.

      In Part A, FluMos-v1 was compared to licensed 2020-2021 QIV Flucelvax (Registered Trademark)
      developed by Seqirus, Inc. and composed of the following 4 influenza strains: Influenza A
      (H1: A/Hawaii/70/2019 (H1N1) pdm09- like virus and H3: A/Hong Kong/45/2019 (H3N2)-like virus)
      and Influenza B: Victoria lineage: B/Washington/02/2019-like virus and Yamagata lineage:
      B/Phuket/3073/2013-like virus).

      In Part B, a higher dose of FluMos-v1 was tested that more closely matches the amount of each
      HA antigen in Flucelvax. The adjuvant Adjuplex (Registered Trademark) was added to FluMos-v1
      to evaluate the potential for increased immunogenicity. All study enrollments and injections
      have been completed, and no further enrollments are planned in this study.

      Adjuplex is provided as a sterile, pyrogen-free, homogeneous solution filled to 0.7 mL in
      3-mL glass vials. Adjuplex is mixed with study products in the pharmacy during preparation
      prior to vaccination at a 20% dose by volume.

      FluMos-v1, FluMos-V1 plus Adjuplex, and Flucelvax (Registered Trademark) are administered
      intramuscularly (IM) in the deltoid muscle via needle and syringe.

      Subjects:

      Healthy adults between the ages of 18-50 years inclusive will be enrolled.

      Study Plan:

      In Part A, the study evaluated the safety, tolerability, and immunogenicity of a single dose
      of FluMos-v1 vaccine alone in a dose-escalation design.

      In Part B, the study evaluated the safety, tolerability, and immunogenicity of a single dose
      of FluMos-v1 vaccine with or without Adjuplex.

      Group 6 and Part C are optional, and a decision was made not to enroll the optional groups
      6-8 in the study. All study enrollments and injections have been completed for groups 1-5,
      and no further enrollments are planned in this study.

      The protocol requires 1 vaccination visit, about 8 follow-up visits, and a telephone contact
      on the day after vaccination. Solicited reactogenicity will be evaluated using a 7-day diary
      card. Assessment of vaccine safety will include clinical observation and monitoring of
      hematological and chemical parameters at clinical visits throughout the study.

      Study Duration:

      Subjects will be evaluated for 40 weeks following vaccine administration and through an
      influenza season.
    

Intervention name(s): VRC-GENADJ0110-AP-NV; Flucelvax; VRC-FLUMOS0111-00-VP (FluMos-v1)
Intervention type(s): Other; Biological; Drug
Intervention description(s): Adjuplex is an adjuvant, a sterile, pyrogen-free adjuvant solution produced by VRC Pilot Plant. Adjuplex comprises highly purified de-oiled soy lecithin and benzene-free carbomer homopolymer formulated in phosphate buffered saline at a pH of 6.5 plus or minus 0.3. Adjuplex adjuvant will be mixed with FluMos-v1 at 20% by volume in the pharmacy during product preparation for the vaccinations of Groups 5A-5B, 6A-6B, and 8A-8B.; Flucelvax is a cell-based vaccine which contains the same four influenza strains selected by the WHO, and has shown better safety and immunogenicity profiles than the traditional licensed seasonal egg based vaccine.; The VRC-FLUMOS0111-00-VP (FluMos-v1) vaccine is composed of engineered pentamer yeast C. albicans lumazine synthase assembled with 20 HA ectodomain trimers from the following influenza strains: Influenza A (H1: A/Idaho/07/2018, H3: A/Perth/1008/2019) and Influenza B (B/Victoria lineage: B/Colorado/06/2017, B/Yamagata lineage: B/Phuket/3073/2013)
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Seasonal Influenza; Flu Virus; Respiratory Illness; Viral Infection; Experimental Vaccine