Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Mosaic Hexavalent Influenza Vaccine VRC-FLUMOS0116-00-VP (FluMos-v2) in Healthy Adults

Study Overview
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Brief Summary
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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 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
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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). The hypotheses are that the FluMos-v2 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 in healthy adults. Secondary objectives are related to 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: The study will evaluate the safety, tolerability, and immunogenicity of FluMos-v2 in a dose escalation design. The protocol requires 2 vaccination visits, approximately 9 follow-up visits, and 2 telephone contacts, one occurring on the day after each 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. The study schema is as follows: VRC 326 Vaccination Schema: 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 Total = 24 subjects (Enrollment up to 35 subjects is permitted if additional subjects are needed for safety or immunogenicity evaluations. Study Duration: Subjects will be evaluated for 40 weeks following first vaccine administration, including through the 2023-2024 influenza season.

Official Title
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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

Conditions
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Influenza

Intervention / Treatment
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* Biological: VRC-FLUMOS0116-00-VP( FLUMos-v2)


Participation Criteria
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Eligibility Criteria
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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 Received at least one licensed influenza vaccine from 2018 through the 2022-2023 influenza season Able and willing to complete the informed consent process Available for clinic visits for 40 weeks after enrollment, including through the 2023-2024 influenza season 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 Agrees to not receive the 2023-2024 licensed influenza vaccination during study participation due to potential confounding of study results Willing to have blood samples collected, stored indefinitely, and used for research purposes Laboratory Criteria within 56 days before enrollment White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval Total lymphocyte count >= 800 cells/microliter Platelets = 125,000 - 500,000 cells/microliter Hemoglobin within institutional normal range or accompanied by the PI or designee approval Alanine aminotransferase (ALT) <= 1.25 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) <= 1.25 x institutional ULN Alkaline phosphatase (ALP) <1.1 x institutional ULN Total bilirubin within institutional normal range or accompanied by the PI or designee approval Serum creatinine <= 1.1 x institutional ULN Negative for HIV infection by an FDA-approved method of detection Criteria applicable to women of childbearing potential: Negative beta-human chorionic gonadotropin (Beta-HCG) pregnancy test (urine or serum) on the day of enrollment Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study for sample collection. EXCLUSION CRITERIA A subject will be excluded if one or more of the following conditions apply: -Breast-feeding or planning to become pregnant during the study Subject has received any of the following substances: More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment Blood products within 16 weeks prior to enrollment Live attenuated vaccines within 4 weeks prior to enrollment Inactivated vaccines within 2 weeks prior to enrollment Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study (Note: SARS-CoV-2 vaccines licensed and/or approved by emergency use authorization are not exclusionary, but are subject to the criteria for timing of inactivated vaccines or mRNA vaccines) mRNA vaccines within 4 weeks prior to enrollment Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule Current anti-TB prophylaxis or therapy Receipt of investigational ferritin-based nanoparticle influenza vaccines, with the exception of participants previously enrolled in the VRC 316 study as follows: Group 2 (HA-F A/Sing prime, HA-F A/Sing boost), 3A (DNA A/Sing prime, HA-F A/Sing boost) or 4A (HA-F A/Sing prime, HA-F A/Sing boost). Receipt of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1) Receipt of any licensed influenza vaccine within 6 months prior to enrollment. Receipt of the 2023-2024 licensed influenza vaccine Subject has a history of any of the following clinically significant conditions: Serious reactions to vaccines that preclude receipt of the study vaccinations as determined by the investigator Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema Asthma that is not well controlled Diabetes mellitus (type I or II), with the exception of gestational diabetes Thyroid disease that is not well controlled Idiopathic urticaria within the past year Autoimmune disease or immunodeficiency Hypertension that is not well controlled Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws Malignancy that is active or history of malignancy that is likely to recur during the period of the study Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen Guillain-Barre Syndrome Any medical, psychiatric, or social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a subject s ability to give informed consent, including but not limited to clinically significant forms of infectious diseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, or heart disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>60 mcg of FluMos-v2 on Day 0 and Week 16 | Biological: VRC-FLUMOS0116-00-VP( FLUMos-v2)<br>* The vaccine, FLUMos-v2, is composed of engineered pentamer yeast C. albican lumazine synthase assembled with 20 HA ectodomain trimers from 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<br>|
| Experimental: Group 2<br>180 mcg of FluMos-v2 on Day 0 and Week16 | Biological: VRC-FLUMOS0116-00-VP( FLUMos-v2)<br>* The vaccine, FLUMos-v2, is composed of engineered pentamer yeast C. albican lumazine synthase assembled with 20 HA ectodomain trimers from 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability | A 60 mcg dose of FluMos-v2 vaccine administered IM via needle on Day 0 and Week 16 to healthy adults. | Through 40 weeks following the first vaccine administration | 
| To evaluate the safety and tolerability | A 180 mcg dose of FluMos-v2 vaccine administered IM administered via needle on Day 0 and Week 16 to healthy adults. | Through 40 weeks following the first vaccine administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the antibody responses to FluMos-v2 vaccine | Antibody responses to a 180 mcg IM dose will be evaluated. | At two weeks after each injection at Week 2 and Week 18 | 
| To evaluate the antibody responses to FluMos-v2 vaccine | Antibody responses to a 60 mcg IM dose will be evaluated. | At two weeks after each injection at Week 2 and Week 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Adults, Seasonal Influenza, Experimental Vaccine, Immune Response, Virus, Universal Influenza Vaccine, Respiratory Illness