Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-VP, in Healthy Adults
Condition: Influenza
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 H10 flu, a flu strain that
      infects humans.

      Objective:

      To test the safety and effectiveness of the H10 Stabilized Stem Ferritin vaccine
      (VRC-FLUNPF0103-00-VP or H10ssF-6473).

      Eligibility:

      Healthy adults ages 18-70, but not born between 1965-1970

      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 on/with/via a diary card for 7 days after each injection. The injection site was
      checked for redness, swelling, itching or bruising.

      Participants had 8-10 follow-up visits over 10 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 collected 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.
    

Detailed description: 
      Design: This was a Phase I, open-label, dose escalation study to evaluate the dose, safety,
      tolerability, and immunogenicity of VRC-FLUNPF0103-00-VP in two regimens. The hypotheses were
      that the vaccine is safe and tolerable and would 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-FLUNPF0103-00-VP (H10ssF-6473), was
      developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious
      Diseases (NIAID) and is composed of the haemagglutinin (HA) stem domain from
      A/Jiangxi/IPB13/2013 (H10N8) influenza genetically fused to the ferritin protein from
      Helicobacter pylori. Purified H10ssF-6473 displays eight well-formed HA trimers that
      antigenically resemble the native H10 stem viral spikes. The vaccine was supplied in
      single-use vials at a concentration of 180 mcg/mL. VRC-PBSPLA043-00-VP consisting of sterile
      phosphate buffered saline (PBS) was the diluent for H10ssF-6473. Prepared study product was
      administered intramuscularly (IM) in the deltoid muscle via needle and syringe.

      Participants:

      Healthy adults between the ages of 18-70 were enrolled; adults born between 1965 and 1970
      were excluded from the trial

      Study Plan: This study evaluated the safety, tolerability and immunogenicity of 1 or 2 doses
      of H10ssF-6473 in a dose-escalation design.

      In Group 1, three participants received a single low dose (20 mcg) of H10ssF-6473 on Day 0.
      For Group 1, the protocol required 1 vaccination visit, 8 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. In
      Group 2A, participants received a higher dose (60 mcg) of H10ssF-6473 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. Groups 2A and 2B were
      stratified by age as shown in the vaccination schema below. For Groups 2A and 2B, the
      protocol required 2 vaccination visits, 10 follow-up visits, and a telephone contact after
      each vaccination.

      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 323 Vaccination Schema:

      Group: 1; Age Cohort: 18-50; Participants: 3; Day 0: 20 mcg IM

      Group: 2A; Age Cohort: 18-50; Participants: 14; Day 0: 60 mcg IM, Week 16: 60 mcg IM

      Group: 2B; Age Cohort: 55-70; Participants: 8; Day 0: 60 mcg IM, Week 16: 60 mcg IM

      Total Participants: 25

      Study Duration:

      Participants were evaluated for 40 weeks following the first vaccine administration.
    

Intervention name(s): VRC-FLUNPF0103-00-VP (H10ssF-6473)
Intervention type(s): Biological
Intervention description(s): The vaccine is composed of the haemagglutinin (HA) stem domain from A/Jiangxi/IPB13/2013 (H10N8) influenza genetically fused to the ferritin protein from H. pylori. Purified H10ssF-6473 displays eight well-formed HA trimers that antigenically resemble the native H10 stem viral spikes.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Dose escalation study
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Flu Virus; Respiratory Illness; Viral Infection; Experimental Vaccine