VRC 326 (001614): A Phase I Open-Label Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Mosaic Hexavalent Influenza Vaccine VRC-FLUMOS0116-00-VP (FluMos-v2) in Healthy Adults
Overview
- Phase
- Phase 1
- Intervention
- VRC-FLUMOS0116-00-VP( FLUMos-v2)
- Conditions
- Influenza
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- To evaluate the safety and tolerability
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
Background:
Influenza (flu) virus causes 3 to 5 million cases of severe illness and up to 650,000 deaths per year worldwide. Current vaccines work well against single strains of flu virus. But no single vaccine works well against all flu viruses that can cause illness.
Objective:
To test an experimental flu vaccine (FluMos-v2) in healthy adults.
Eligibility:
Healthy adults aged 18 to 50 years.
Design:
Participants will have 11 clinic visits in 10 months. They must agree not to get a licensed flu vaccine while taking part in this study.
FluMos-v2 will be given with a needle injected into a muscle in the upper arm. Participants will receive a follow-up phone call the following day.
Participants will be given a diary card, a ruler, and a thermometer. They will take their temperature every day for 7 days after receiving the shot. They will measure any skin changes at the injection site. They will record their findings and how they feel.
Participants will receive a second FluMos-v2 shot after 4 months. They will repeat the other follow-up steps.
Participants will have 9 other clinic follow-up visits. Blood will be drawn at each visit.
Participants should also come to the clinic if they develop flu-like symptoms during the study.
Participants may opt for an apheresis 2 weeks after each shot: Blood will be removed through a needle in the vein of 1 arm. The blood will run through a machine that separates out the white blood cells. The remaining blood is returned through a needle in the other arm.
Detailed Description
Design: This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of the mosaic hexavalent influenza vaccine VRC-FLUMOS0116-00-VP (FluMos-v2). For Part A, the hypotheses are that the FluMos-v2 vaccine is safe and tolerable and will elicit an immune response. For Part B, the hypothesis is that the vaccine will generate a germinal center (GC) response in a draining lymph node as determined by fine needle aspiration of a reactive ipsilateral axillary lymph node. The primary objective is to evaluate the safety and tolerability of the investigational vaccine in healthy adults. Secondary objectives are related to the immunogenicity of the investigational vaccine. Study Products: The investigational vaccine, FluMos-v2, was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID) and is composed 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 FluMos-v2 is supplied in a single-use vial at a target concentration of 180 mcg/mL and will be 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, this study evaluates the safety, tolerability, and immunogenicity of FluMos-v2 in a dose escalation design. In Part B, this study assesses GC and peripheral blood immune responses at different time points after vaccination with FluMos-v2. For Part B: The protocol requires 2 vaccination visits, approximately 9-10 follow-up visits, 4 mandatory FNA visits and 1 optional FNA visit, and 10-12 telephone contacts. Safety phone calls occur one day after each vaccination, and 3 days after each FNA. Additional phone calls are related to scheduling the FNA procedures. Solicited reactogenicity is evaluated using a 7-day diary card. Assessment of vaccine safety includes clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study. The study schema is as follows: VRC 326 Vaccination Schema Part A: Group 1: Subjects:12, Day 0: 60 mcg, Week 16: 60 mcg, Product: FluMos-v2 Group 2: Subjects: 12, Day 0: 180 mcg, Week 16: 180 mcg, Product: FluMos-v2 Part B: Group 3: Subjects: 6, Day 0: 180 mcg, Week 16: 180 mcg, Product: FluMos-v2 Total = 30 subjects (Enrollment up to 40 subjects is permitted if additional subjects are needed for safety or immunogenicity evaluations). Study Duration: Part A: Subjects are evaluated for 40 weeks following first vaccine administration, including through the 2023-2024 influenza season. Part B: Subjects are evaluated for 40 weeks following the first vaccine administration, including through the 2024-2025 influenza season.
Investigators
Eligibility Criteria
Inclusion Criteria
- •INCLUSION CRITERIA:
- •A subject must meet all of the following criteria:
- •Healthy adults between the ages of 18-50 years, inclusive
- •Based on history and physical examination, in good general health and without history of any of the conditions listed in the
Exclusion Criteria
- •For Part A: Received at least one licensed influenza vaccine from 2018 through the 2022-2023 influenza season
- •Able and willing to complete the informed consent process
- •For Part A: Available for clinic visits for 40 weeks after enrollment, including through the 2023-2024 influenza season
- •For Part B: Available for clinic visits for 40 weeks after enrollment, including through the 2024-2025 influenza season
- •For Part B: Agrees to undergo four lymph node FNAs.
- •Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
- •Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) \<= 35 within the 56 days before enrollment
- •For both Parts A and B: Agrees to not receive any licensed influenza vaccine during study participation due to potential confounding of study results
- •Willing to have blood samples collected, stored indefinitely, and used for research purposes
- •For Part B: Willing to have lymph node samples collected, stored indefinitely, and used for research purposes
Arms & Interventions
Group 1
60 mcg of FluMos-v2 on Day 0 and Week 16
Intervention: VRC-FLUMOS0116-00-VP( FLUMos-v2)
Group 2
180 mcg of FluMos-v2 on Day 0 and Week16
Intervention: VRC-FLUMOS0116-00-VP( FLUMos-v2)
Group 3
180 mcg of FluMos-v2 on Day 0 and Week16
Intervention: VRC-FLUMOS0116-00-VP( FLUMos-v2)
Outcomes
Primary Outcomes
To evaluate the safety and tolerability
Time Frame: Through 40 weeks following the first vaccine administration
A 60 mcg dose of FluMos-v2 vaccine administered IM via needle on Day 0 and Week 16 to healthy adults.
Secondary Outcomes
- To evaluate the antibody responses to FluMos-v2 vaccine(At two weeks after each injection at Week 2 and Week 18)