First-in-Human Clinical Trial of a Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV, in Healthy Adults
Study Details
Study Description
Brief 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 who received at least one licensed flu vaccine from 2016 through the 2019-2020 influenza season.
Design:
Participants will be screened through a separate protocol.
Participants will be tested for COVID-19. They may have a pregnancy test.
Participants will receive the FluMos-v1 vaccine or the Flucelvax vaccine. It will be injected in the upper arm.
Participants will complete a diary card for 7 days. They will record any symptoms they have. They will be given a thermometer to check their temperature. They will also be given a ruler to measure any skin changes at the injection site.
Participants will have about 10 study visits. They will be asked how they are feeling and if they have taken any medications. They will have blood drawn.
Participants will have oral mucosal samples collected using a thin swab. They may have nose and throat secretions collected using a thin swab.
Some participants will have optional apheresis. Blood will be removed through a needle in a vein in one arm. A machine will separate the white blood cells. The rest of the blood will be returned through a needle in a vein in the other arm.
Participation will last for 40 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is 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 are that the FluMos-v1 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 and dosing regimen compared with the licensed inactivated seasonal Flucelvax (Registered Trademark) quadrivalent influenza vaccine (QIV) in Healthy Adults.
The investigational vaccine FluMos-v1 was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID) and is composed of the following 4 influenza strains:
Influenza A:
H1: A/Idaho/07/2018
H3: A/Perth/1008/2019
Influenza B:
B/Victoria lineage: B/Colorado/06/2017
B/Yamagata lineage: B/Phuket/3073/2013
FluMos-v1 is supplied in a single-use vial at a concentration of 180 mcg/mL.
The FDA licensed inactivated 2020-2021 QIV Flucelvax(Registered Trademark) was developed by
Seqirus, Inc. and is composed of the following 4 influenza strains:
Influenza A:
H1: A/Hawaii/70/2019 (H1N1) pdm09-like virus
H3: A/Hong Kong/45/2019 (H3N2)-like virus
Influenza B:
B/Victoria lineage: B/Washington/02/2019-like virus
B/Yamagata lineage: B/Phuket/3073/2013-like virus
Flucelvax(Registered Trademark) is supplied in a single-use syringe at 15 mcg HA of each of the four influenza strains, for a total of 60 mcg HA per 0.5 mL dose.
FluMos-v1 and Flucelvax(Registered Trademark) will be administered intramuscularly (IM) in the deltoid muscle via needle and syringe.
Healthy adults between the ages of 18-50 years inclusive will be enrolled.
The study will evaluate the safety, tolerability and immunogenicity of a single dose of FluMos-v1 vaccine in a dose-escalation design. In Group 1A-1B, five subjects will receive a dose of 20 mcg of FluMos-v1. If the 20 mcg dose is assessed as safe and tolerable, enrollment will begin for Group 2A-2B.
In Group 2A-2B, subjects will receive a dose of 60 mcg of FluMos-v1. In Group 3A-3B, subjects will receive the licensed QIV Flucelvax(Registered Trademark) and may enroll at any time after the study is open to accrual.
The protocol requires 1 vaccination visit, about 8 follow-up visits, and a telephone contact on the day after vaccination. For all groups, 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.
Subjects will be evaluated for 40 weeks following vaccine administration and through an influenza season.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 1A-1B 20 mcg of FluMos-v1 |
Biological: VRC-FLUMOS0111-00-VP (FluMos-v1)
The VRC-FLUMOS0111-00-VP (FluMos-v1) vaccine is composed of engineered pentamer yeast C. albicans lumazine synthase assembled with 20 HA ectodomain trimers from the following influenza strains: Influenza A (H1: A/Idaho/07/2018, H3: A/Perth/1008/2019) and Influenza B (B/Victoria lineage: B/Colorado/06/2017, B/Yamagata lineage: B/Phuket/3073/2013)
|
| Experimental: Group 2A-2B 60 mcg of FluMos-v1 |
Biological: VRC-FLUMOS0111-00-VP (FluMos-v1)
The VRC-FLUMOS0111-00-VP (FluMos-v1) vaccine is composed of engineered pentamer yeast C. albicans lumazine synthase assembled with 20 HA ectodomain trimers from the following influenza strains: Influenza A (H1: A/Idaho/07/2018, H3: A/Perth/1008/2019) and Influenza B (B/Victoria lineage: B/Colorado/06/2017, B/Yamagata lineage: B/Phuket/3073/2013)
|
| Active Comparator: Group 3A-3B standard dose of 60 mcg of the licensed QIV Flucelvax |
Biological: Flucelvax
Flucelvax is a cell-based vaccine which contains the same four influenza strains selected by the WHO, and has shown better safety and immunogenicity profiles than the traditional licensed seasonal egg based vaccine.
|
Outcome Measures
Primary Outcome Measures
- Serious adverse events [Day 0 through Day 280]
Occurrence of serious adverse events
- New chronic medical conditions [Day 0 through Day 280]
Occurrence of new-onset of chronic medical conditions
- Local Reactogenicity [7 days after product administration]
Occurrence of local reactogenicity signs and symptoms
- Unsolicited adverse events [Day 0 through 28 days post product administration]
Occurrence of unsolicited non-serious adverse events
- Laboratory measures [Day 0 through 28 days post product administration]
Occurrence of laboratory safety measures
- Systemic Reactogenicity [7 days after product administration]
Occurrence of systemic reactogenicity signs and symptoms
Secondary Outcome Measures
- Group 1A-1B: vaccine-induced antibodies [2 weeks after product administration]
antibody responses to FluMos-v1
- Group 2A-2B: vaccine-induced antibodies [2 weeks after product administration]
antibody responses to FluMos-v1
Eligibility Criteria
Criteria
- INCLUSION CRITERIA:
A subject must meet all of the following criteria:
-
Healthy adults between the ages of 18-50 years inclusive
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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 2016 through the 2019-2020 influenza season
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Able and willing to complete the informed consent process
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Available for clinic visits for 40 weeks after enrollment and through an influenza season
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Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
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Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) <=35 within the 56 days before enrollment
Laboratory Criteria within 56 days before enrollment
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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
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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)
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Aspartate aminotransferase (AST) <=1.25 x institutional ULN
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Alkaline phosphatase (ALP) <1.1 x institutional ULN
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Total bilirubin within institutional normal range or accompanied by the PI or designee approval.
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Serum creatinine <=1.1 x institutional ULN
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Negative for HIV infection by an FDA-approved method of detection
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Negative for SARS-CoV-2 prior to enrollment
Criteria applicable to women of childbearing potential:
-
Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on the day of enrollment
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Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study
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
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Blood products within 16 weeks prior to enrollment
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Live attenuated vaccines within 4 weeks prior to enrollment
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Inactivated vaccines within 2 weeks prior to enrollment
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Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study
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Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule
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Current anti-TB prophylaxis or therapy
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Previous investigational H1, H2, or H10 influenza vaccines
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Groups 1A, 2A, and 3A only: Receipt of the 2020-2021 season s licensed influenza vaccine at any time prior to enrollment
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Groups 1B, 2B, and 3B only: Receipt of the 2020-2021 season s licensed influenza vaccine within 4 months prior to enrollment.
Subject has a history of any of the following clinically significant conditions:
-
Serious reactions to vaccines that preclude receipt of the study vaccination as determined by the investigator
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Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
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Asthma that is not well controlled
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Diabetes mellitus (type I or II), with the exception of gestational diabetes
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Thyroid disease that is not well controlled
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Idiopathic urticaria within the past year
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Autoimmune disease or immunodeficiency
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Hypertension that is not well controlled
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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
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Malignancy that is active or history of malignancy that is likely to recur during the period of the study
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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
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Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
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Guillain-Barre Syndrome
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Previous or current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) documented by PCR test
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Any medical, psychiatric, 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Principal Investigator: Alicia T Widge, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Kanekiyo M, Joyce MG, Gillespie RA, Gallagher JR, Andrews SF, Yassine HM, Wheatley AK, Fisher BE, Ambrozak DR, Creanga A, Leung K, Yang ES, Boyoglu-Barnum S, Georgiev IS, Tsybovsky Y, Prabhakaran MS, Andersen H, Kong WP, Baxa U, Zephir KL, Ledgerwood JE, Koup RA, Kwong PD, Harris AK, McDermott AB, Mascola JR, Graham BS. Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses. Nat Immunol. 2019 Mar;20(3):362-372. doi: 10.1038/s41590-018-0305-x. Epub 2019 Feb 11. Erratum in: Nat Immunol. 2019 Apr 12;:.
- Lambert LC, Fauci AS. Influenza vaccines for the future. N Engl J Med. 2010 Nov 18;363(21):2036-44. doi: 10.1056/NEJMra1002842. Review.
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