NCT04896086

First-in-Human Clinical Trial of a Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV in Healthy Adults

VRC 325 (000410): A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability and Immunogenicity of Mosaic Quadrivalent Influenza Vaccine With and Without Adjuplex Compared With a Licensed Inactivated Seasonal QIV, In Healthy Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 63 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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 years inclusive were enrolled. Design: Participants were screened through a separate protocol. Participants were tested for COVID-19. They may have had a pregnancy test. Participants received the investigational FluMos-v1 vaccine or the licensed inactivated seasonal quadrivalent influenza vaccine Flucelvax injected in the upper arm. Participants completed a diary card for 7 days. They recorded any symptoms they had. They were given a thermometer to check their temperature. They were also given a ruler to measure any skin changes at the injection site. Participants had about 10 study visits. They were asked how they were feeling and if they had taken any medications. They had blood drawn. Some participants had an optional apheresis. Blood was removed through a needle in a vein in one arm. A machine separated the white blood cells. The rest of the blood was returned through a needle in a vein in the other arm. Participation lasted for 40 weeks.

Detailed description

Design: This was 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 were that the FluMos-v1 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 alone or with adjuvant in healthy adults. Secondary objectives were related 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 nanoparticle vaccine VRC-FLUMOS0111-00-VP (FluMos-v1) was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID). FluMos-v1 is composed of engineered pentameric promoters based on C. albicans lumazine synthase assembled with 20 trimeric promoters displaying HA ectodomains. It contains hemagglutinin (HA) proteins from the following 4 influenza strains: A/Idaho/07/2018, A/Perth/1008/2019, B/Colorado/06/2017 and B/Phuket/3073/2013. FluMos-v1 was 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) that was developed by Seqirus, Inc. and formulated with the following 4 influenza strains: A/Hawaii/70/2019 (H1N1) pdm09-like virus, A/Hong Kong/45/2019 (H3N2)-like virus, B/Washington/02/2019-like virus, and 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. Adjuplex is a sterile, pyrogen-free adjuvant solution produced by the 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 was provided as a sterile, pyrogen-free, homogeneous solution filled to 0.7 mL in 3-mL glass vials. Adjuplex was 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 were administered intramuscularly (IM) in the deltoid muscle via needle and syringe. Participants: A total of 63 participants enrolled as follows: Part A Part A, Group 1 (20 mcg FluMos-v1): 5 participants Group 1A (N=1): Did not receive 2020-2021 season's licensed influenza vaccine at any time prior to enrollment Group 1B (N=4): Receipt of the 2020-2021 season's licensed influenza vaccine more than 4 months prior to enrollment Part A, Group 2 (60 mcg FluMos-v1): 15 participants Group 2A (N=4): Did not receive 2020-2021 season's licensed influenza vaccine at any time prior to enrollment Group 2B (N=11): Receipt of the 2020-2021 season's licensed influenza vaccine more than 4 months prior to enrollment Part A, Group 3 (60 mcg Flucelvax®): 15 participants Group 3A (N=3): Did not receive 2020-2021 season's licensed influenza vaccine at any time prior to enrollment Group 3B (N=12): Receipt of the 2020-2021 season's licensed influenza vaccine more than 4 months prior to enrollment Part B Part B, Group 4 (100 mcg FluMos-v1): 15 participants Group 4A (N=1): Did not receive 2021-2022 or 2022-2023 season's licensed influenza vaccine at any time prior to enrollment Group 4B (N=14): Receipt of the 2021-2022 or 2022-2023 season's licensed influenza vaccine more than 4 months prior to enrollment Part B, Group 5 (100 mcg FluMos-v1 + Adjuplex (20% v/v)): 13 participants Group 5A (N=2): Did not receive 2021-2022 or 2022-2023 season's licensed influenza vaccine at any time prior to enrollment Group 5B (N=11): Receipt of the 2021-2022 or 2022-2023 season's licensed influenza vaccine more than 4 months prior to enrollment 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 were optional, and a decision was made not to enroll the optional Groups 6-8 in the study. The protocol required 1 vaccination visit, about 8 follow-up visits, and a telephone contact on the day after vaccination. Solicited reactogenicity were 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. Study Duration: Participants were evaluated for 40 weeks following vaccine administration including through an influenza season.

Conditions

• Influenza
• Seasonal Influenza

Interventions

Type	Name	Description
DRUG	VRC-GENADJ0110-AP-NV (Adjuplex)	Adjuplex is a sterile, pyrogen-free adjuvant solution produced by the VRC Pilot Plant. Adjuplex comprises highly purified de-oiled soy lecithin and benzene-free carbomer homopolymer formulated in phosphate buffered saline. Adjuplex adjuvant was mixed with FluMos-v1 at 20% by volume in the pharmacy during product preparation for the vaccinations of Groups 5A-5B.
BIOLOGICAL	Flucelvax	Flucelvax is an inactivated influenza vaccine licensed for the 2020-2021 season.
DRUG	VRC-FLUMOS0111-00-VP (FluMos-v1)	FluMos-v1 investigational vaccine is composed of engineered pentameric promoters based on C. albicans lumazine synthase assembled with 20 trimeric promoters displaying HA ectodomains. It contains hemagglutinin (HA) proteins from the following 4 influenza strains: A/Idaho/07/2018, A/Perth/1008/2019, B/Colorado/06/2017 and B/Phuket/3073/2013.

Timeline

• Start date: 2021-05-24
• Primary completion: 2024-01-25
• Completion: 2024-01-25
• First posted: 2021-05-21
• Last updated: 2025-04-27
• Results posted: 2025-03-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study