Clinical trial NCT04896086: First-in-Human Clinical Trial of a Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Seasonal Influenza
Keywords: Seasonal Influenza
Flu Virus
Respiratory Illness
Viral Infection
Experimental Vaccine
Nanoparticle Vaccine
Adjuvant
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2021-05-21
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation
Primary purpose: PREVENTION

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 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.

Eligibility criteria: * INCLUSION CRITERIA:

Participant must have met all of the following criteria:

1. Healthy adults between the ages of 18-50 years inclusive
2. Based on history and physical examination, in good general health and without history of any of the conditions listed in the exclusion criteria
3. Part A: Received at least one licensed influenza vaccine from 2016 through the 2019-2020 influenza season
4. Part B: Received at least one licensed influenza vaccine from 2017 through the 2022-2023 influenza season
5. Able and willing to complete the informed consent process
6. Available for clinic visits for 40 weeks after enrollment and through an influenza season
7. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
8. 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
9. White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval
10. Total lymphocyte count \>=800 cells/microliter
11. Platelets = 125,000 - 500,000 cells/microliter
12. Hemoglobin within institutional normal range or accompanied by the PI or designee approval
13. Alanine aminotransferase (ALT) \<=1.25 x institutional upper limit of normal (ULN)
14. Aspartate aminotransferase (AST) \<=1.25 x institutional ULN
15. Alkaline phosphatase (ALP) \<1.1 x institutional ULN
16. Total bilirubin within institutional normal range or accompanied by the PI or designee approval.
17. Serum creatinine \<=1.1 x institutional ULN
18. Negative for HIV infection by an FDA-approved method of detection

    Criteria applicable to women of childbearing potential:
19. Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on the day of enrollment
20. 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:

Participant was excluded if one or more of the following conditions applied:

1. Breast-feeding or planning to become pregnant during the study

   Participant received any of the following substances:
2. 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
3. Blood products within 16 weeks prior to enrollment
4. Live attenuated vaccines within 4 weeks prior to enrollment
5. Inactivated vaccines within 2 weeks prior to enrollment
6. Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study
7. Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule
8. Current anti-TB prophylaxis or therapy
9. Previous investigational H1, H2, or H10 influenza vaccines, including Part A participants
10. Part A:

    1. Groups 1A, 2A, and 3A only: Receipt of the 2020-2021 season's licensed influenza vaccine at any time prior to enrollment
    2. Groups 1B, 2B, and 3B only: Receipt of the 2020-2021 season's licensed influenza vaccine within 4 months prior to enrollment.
11. Part B and C:

    1. Groups 4A and 5A only: Receipt of the 2021-2022 or 2022-2023 season's licensed influenza vaccine at any time prior to enrollment
    2. Groups 4B and 5B only: Receipt of the 2021-2022 or 2022-2023 season's licensed influenza vaccine within 4 months prior to enrollment.

    Participant had a history of any of the following clinically significant conditions:
12. Serious reactions to vaccines that preclude receipt of the study vaccination as determined by the investigator
13. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
14. Asthma that is not well controlled
15. Diabetes mellitus (type I or II), with the exception of gestational diabetes
16. Thyroid disease that is not well controlled
17. Idiopathic urticaria within the past year
18. Autoimmune disease or immunodeficiency
19. Hypertension that is not well controlled
20. 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
21. Malignancy that is active or history of malignancy that is likely to recur during the period of the study
22. 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
23. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
24. Guillain-Barre Syndrome
25. 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 participant's ability to give informed consent.

Primary outcomes:
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration
timeFrame: 7 days after product administration
measure: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Product Administration
timeFrame: 7 days after product administration
measure: Number of Participants With Serious Adverse Events (SAEs) Following Product Administration
timeFrame: Day 0 after product administration through Day 280, up to Week 40
measure: Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration
timeFrame: Day 0 through 28 days post product administration, up to Week 4
measure: Number of Participants With New Chronic Medical Conditions Following Product Administration
timeFrame: Day 0 after product administration through Day 280, up to Week 40
measure: Number of Participants With Abnormal Laboratory Measures of Safety Following Product Administration
timeFrame: Day 0 through 28 days post product administration, up to Week 4
measure: Number of Participants With Influenza or Influenza-like Illness (ILIs) Following Product Administration
timeFrame: Day 0 after product administration through Day 280, up to Week 40
Secondary outcomes:
measure: Antibody Response Following the Completion of Vaccination
timeFrame: Baseline to 2 weeks after product administration
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Lesia Dropulic, M.D.
role: PRINCIPAL_INVESTIGATOR
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