NCT06863142 | RECRUITING | Influenza Prevention

Detailed Description:

Design: This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of mosaic hexavalent influenza vaccine VRC-FLUMOS0116-00-VP (FluMos-v2) with and without Army Liposome Formulation containing saponin QS-21 (ALFQ) adjuvant. The hypotheses are that the FluMos-v2 vaccine is safe and tolerable when administered alone or with ALFQ adjuvant, that this vaccine elicits antigen-specific immune responses, and that addition of the ALFQ adjuvant increases the magnitude and breadth of the elicited immune responses. The primary objective is to evaluate the safety and tolerability of the investigational vaccine with and without ALFQ adjuvant in healthy adults. Secondary objectives are related to the immunogenicity of the investigational vaccine with and without ALFQ adjuvant. Study Products: The investigational vaccine FluMos-v2 was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID). The adjuvant, Army Liposome Formulation containing QS-21 (ALFQ), was developed, and provided by the Walter Reed Army Institute of Research (WRAIR). The FluMos-v2 vaccine is composed of full-length HA trimers of the following 6 influenza strains: Influenza A: H1: A/Idaho/07/2018 H2: A/Singapore/1/1957 H3: A/Perth/1008/2019 H3: A/Darwin/106/2020 Influenza B: B/Victoria lineage: B/Colorado/06/2017 B/Yamagata lineage: B/Phuket/3073/2013 VRC-FLUMOS0116-00-VP (FluMos-v2) is a sterile, aqueous buffered solution supplied in 3.0 mL single-dose glass vials containing 0.7 +/- 0.1 mL with a vaccine concentration of 180 mcg/mL. The ALFQ drug product is a sterile suspension that contains 240 mcg of monophosphoryl 3-deacyl Lipid A (3D-PHAD(R)) and 120 mcg QS-21 that is vialed at 0.6 mL/vial in 3.0 mL glass vials. 0.5 mL of ALFQ adjuvant will be mixed with the 60 or 180 mcg dose of FluMos-v2 during preparation in the pharmacy prior to vaccination. FluMos-v2 with and without ALFQ adjuvant will be administered intramuscularly (IM) in the deltoid muscle via needle and syringe. Participants: Healthy adults 18-50 years of age, inclusive, will be enrolled. Study Plan: Group 1 will open and enroll without any planned dose safety reviews, because the 180 mcg dose without adjuvant was evaluated as safe and tolerable in VRC 326 study. The adjuvanted dose groups, Groups 2, 3A, and 3B will proceed with the lower dose group enrolling first. There will be two interim dose safety reviews in this trial: the first will review the safety data for Group 2 (60 mcg of FluMos-v2 with ALFQ adjuvant). Enrollment for Group 2 will be limited to one participant per day for the first three participants. After the third participant's two-week post-vaccination visit, a safety review will decide whether to continue at the same dose level in Group 2 and open Group 3A and Group 3B to participants who will receive 180 mcg of FluMos-v2 with ALFQ adjuvant. Enrollment for Group 3A or Group 3B will also be limited to one participant per day for the first three participants. The second safety review is a dose continuation review for Group 3A and Group 3B (180 mcg of FluMos-v2 with ALFQ adjuvant). After the third participant's two-week post-vaccination visit, a safety review will determine whether to continue at the same dose level in Group 3A or Group 3B. Once all groups are open, participants will continue enrollment into each group at the discretion of the Principal Investigator (PI) to balance the number of enrollments in each group. If a current participant is discontinued from the protocol, a new participant may be enrolled at the discretion of the PI in order to collect required safety or immunogenicity data. 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. The study schema is as follows: VRC 328 Vaccination Schema Group - 1 Participants - 12 Day 0 - 180 mcg Week 16 - 180 mcg Product - FluMos-v2 Group - 2 Participants - 5 Day 0 - 60 mcg Week 16 - 60 mcg Product - FluMos-v2 + 0.5 mL ALFQ Group - 3A Participants - 12 Day 0 - 180 mcg Week 16 - 180 mcg Product - FluMos-v2 + 0.5 mL ALFQ Group - 3B\* Participants - 0-6 Day 0 - 180 mcg Week 16 - 180 mcg Product - FluMos-v2 + 0.5 mL ALFQ Total Participants - 35\*\* \*Enrollment in Group 3B is optional and includes participants who have previously taken part in the following influenza vaccine studies: VRC 316 (ONLY participants enrolled in Groups 2, 3A, and 4A; HA-F A/Sing or DNA A/Sing vaccines) or VRC 321 (H1ssF_3928 vaccine) or VRC 323 (H10ssF-6473 vaccine). \*\*Enrollment of up to 45 participants is permitted if additional participants are needed for safety or immunogenicity evaluations. Study Duration: Participants will be evaluated for 68 weeks following the first vaccine administration, including through the 2025-2026 influenza season.