First-in-Human Clinical Trial of a Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV, in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04896086
• Recruitment Status: Active, not recruiting
• First Posted: May 21, 2021
• Last Update Posted: May 9, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information

• First Submitted Date: May 20, 2021
• First Posted Date: May 21, 2021
• Last Update Posted Date: May 9, 2023
• Actual Study Start Date: May 24, 2021
• Estimated Primary Completion Date: January 25, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2021)

• Serious adverse events [ Time Frame: Day 0 through Day 280 ]
  Occurrence of serious adverse events
• New chronic medical conditions [ Time Frame: Day 0 through Day 280 ]
  Occurrence of new-onset of chronic medical conditions
• Local Reactogenicity [ Time Frame: 7 days after product administration ]
  Occurrence of local reactogenicity signs and symptoms
• Unsolicited adverse events [ Time Frame: Day 0 through 28 days post product administration ]
  Occurrence of unsolicited non-serious adverse events
• Laboratory measures [ Time Frame: Day 0 through 28 days post product administration ]
  Occurrence of laboratory safety measures
• Systemic Reactogenicity [ Time Frame: 7 days after product administration ]
  Occurrence of systemic reactogenicity signs and symptoms

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 7, 2022)

• Part B: Group 4A-4B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to 100 mcg of FluMos-v1 as a single dose
• Part B: Groups 4A-4B and 5A-5B [ Time Frame: 2 weeks after product administration ]
  Evaluate antibody responses between 100 mcg of FluMos-v1 and FluMos-v1 plus Adjuplex
• Part B: Group 6A-6B: If Enrolled: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to 60 mcg of FluMos-v1 plus Adjuplex as a single dose
• Part A: Group 1A-1B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to 20 and 60 mcg of FluMos-v1 as a single dose
• Part A: Group 2A-2B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to 60 mcg of FluMos-v1 as a single dose
• Part B: Group 5A-5B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to 100 mcg of FluMos-v1 plus Adjuplex as a single dose
• Part A: Group 3A-3B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to 60 of FluMos-v1 and Flucelvax as a single dose

Original Secondary Outcome Measures (submitted: May 20, 2021)

• Group 1A-1B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to FluMos-v1
• Group 2A-2B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ]
  antibody responses to FluMos-v1

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

Detailed Description

Design:

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 alone or with adjuvant in healthy adults. Secondary objectives relate 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 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 and H3: A/Perth/1008/2019) and Influenza B (Victoria lineage: B/Colorado/06/2017 and Yamagata lineage: B/Phuket/3073/2013. FluMos-v1 is 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 developed by Seqirus, Inc. and composed of the following 4 influenza strains: Influenza A (H1: A/Hawaii/70/2019 (H1N1) pdm09-like virus and H3: A/Hong Kong/45/2019 (H3N2)-like virus) and Influenza B: Victoria lineage: B/Washington/02/2019-like virus and Yamagata lineage: B/Phuket/3073/2013-like virus).

With the addition of Parts B and C in protocol V2.0, a higher dose of FluMos-v1 will be tested that more closely matches the amount of each HA antigen in Flucelvax. If the higher dose is safe and well tolerated, then the adjuvant Adjuplex (Registered Trademark) will be added to FluMos-v1 to evaluate the potential for increased immunogenicity.

Adjuplex will be provided as a sterile, pyrogen-free, homogeneous solution filled to 0.7 mL in 3-mL glass vials. Adjuplex will be mixed with study products in the pharmacy during preparation prior to vaccination at a 20 percent dose by volume.

FluMos-v1, FluMos-V1 plus Adjuplex, and Flucelvax (Registered Trademark) are 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, 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 will evaluate the safety, tolerability and immunogenicity of a single dose of FluMosv1 vaccine with or without Adjuplex.

Part C will be conducted, after IRB approval, if more subjects are needed to evaluate the safety, tolerability and immunogenicity of a single dose of FluMos-v1 plus Adjuplex and may include doses up to a max of 190 mcg.

The protocol requires 1 vaccination visit, about 8 follow-up visits, and a telephone contact on the day after 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.

Study Duration:

Subjects will be evaluated for 40 weeks following vaccine administration and through an influenza season.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Influenza
• Seasonal Influenza

Intervention

• Other: VRC-GENADJ0110-AP-NV
  Adjuplex is an adjuvant, a sterile, pyrogen-free adjuvant solution produced by 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 adjuvant will be mixed with FluMos-v1 at 20% by volume in the pharmacy during product preparation for the vaccinations of Groups 5A-5B, 6A-6B, and 8A-8B.
• 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.
• Drug: 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)

Study Arms

• Experimental: Group 1A-1B
  20 mcg of FluMos-v1
  Intervention: Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)
• Experimental: Group 2A-2B
  60 mcg of FluMos-v1
  Intervention: Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)
• Active Comparator: Group 3A-3B
  standard dose of 60 mcg of the licensed QIV Flucelvax
  Intervention: Biological: Flucelvax
• Experimental: Group 4A-4B
  100 mcg of FluMos-v1
  Intervention: Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)
• Experimental: Group 5A-5B
  100 mcg of FluMos-v1 plus Adjuplex
  Interventions:

  • Other: VRC-GENADJ0110-AP-NV
  • Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)
• Experimental: Group 6A-6B
  Optional: 60 mcg of FluMos-v1 plus Adjuplex
  Interventions:

  • Other: VRC-GENADJ0110-AP-NV
  • Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)
• Experimental: Group 7A-7B
  Optional: TBD mcg of FluMos-v1
  Intervention: Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)
• Experimental: Group 8A-8B
  Optional: TBD of FluMos-v1 plus Adjuplex
  Interventions:

  • Other: VRC-GENADJ0110-AP-NV
  • Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)

Publications *

• Lambert LC, Fauci AS. Influenza vaccines for the future. N Engl J Med. 2010 Nov 18;363(21):2036-44. doi: 10.1056/NEJMra1002842. No abstract available.
• 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;:

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 5, 2023): 35
• Original Estimated Enrollment (submitted: May 20, 2021): 40
• Estimated Study Completion Date: January 25, 2024
• Estimated Primary Completion Date: January 25, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

• INCLUSION CRITERIA:

A subject must meet 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 and C: 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

8. White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval

9. Total lymphocyte count >=800 cells/microliter

10. Platelets = 125,000 - 500,000 cells/microliter

11. Hemoglobin within institutional normal range or accompanied by the PI or designee approval

12. Alanine aminotransferase (ALT) <=1.25 x institutional upper limit of normal (ULN)

13. Aspartate aminotransferase (AST) <=1.25 x institutional ULN

14. Alkaline phosphatase (ALP) <1.1 x institutional ULN

15. Total bilirubin within institutional normal range or accompanied by the PI or designee approval.

16. Serum creatinine <=1.1 x institutional ULN

17. Negative for HIV infection by an FDA-approved method of detection

18. Negative for SARS-CoV-2 prior to enrollment

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:

A subject will be excluded if one or more of the following conditions apply:

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

   Subject has 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, 5A, 6A, 7A, and 8A only: Receipt of the 2021-2022 or 2022-2023 season s licensed influenza vaccine at any time prior to enrollment
    2. Groups 4B, 5B, 6B, 7B, and 8B only: Receipt of the 2021-2022 or 2022-2023 season s licensed influenza vaccine within 4 months prior to enrollment.

    Subject has 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 subject s ability to give informed consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04896086
• Other Study ID Numbers: 10000410; 000410-I
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: .Only aggregate data will be shared.

• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Richard L Wu, M.D.; National Institute of Allergy and Infectious Diseases (NIAID)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: May 5, 2023