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

NCT04896086 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 10000410000410-I
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza; Seasonal Influenza

Keywords

Seasonal Influenza; Flu Virus; Respiratory Illness; Viral Infection; Experimental Vaccine; Nanoparticle Vaccine; Adjuvant

Outcome Measures

Primary Outcomes (7)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration

  Participants recorded the occurrence of solicited local symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.

  7 days after product administration

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Product Administration

  Participants recorded the occurrence of solicited systemic symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.

  7 days after product administration

• Number of Participants With Serious Adverse Events (SAEs) Following Product Administration

  SAEs were recorded from receipt of product administration through the last study visit at Week 40. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after product administration through Day 280, up to Week 40

• Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration

  Unsolicited AEs and attribution assessments were recorded in the study database from receipt of study product administration through the visit scheduled for 4 weeks after study product administration. At other time periods greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), influenza-like illness (ILI) or influenza and new chronic medical conditions that required ongoing medical management (reported as separate outcomes) were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through 28 days post product administration, up to Week 4

• Number of Participants With New Chronic Medical Conditions Following Product Administration

  New chronic medical conditions that required ongoing medical management were recorded from receipt of study product administration through the last expected study visit at Week 40. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after product administration through Day 280, up to Week 40

• Number of Participants With Abnormal Laboratory Measures of Safety Following Product Administration

  Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil percents/counts) and chemistry (alanine aminotransferase (ALT), alanine aspartate (AST), alkaline phosphate (ALP), creatinine and total bilirubin). Complete Blood Count (CBC) with differential, total bilirubin, AST, ALT, and ALP results were collected at Baseline, Day 0, Day 14, and 28. Creatinine results were collected at Baseline, Day 0 and Day 14. Institutional lab normal ranges as well as Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.

  Day 0 through 28 days post product administration, up to Week 4

• Number of Participants With Influenza or Influenza-like Illness (ILIs) Following Product Administration

  Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the study product administration through the last study visit. ILI was defined as fever (temperature of 100 degrees F \[37.8 degrees C\] or greater) and a cough and/or sore throat in the absence of a known cause other than influenza. Collection of nasopharyngeal swabs were used for laboratory confirmation of influenza by polymerase chain reaction (PCR) in participants who met criteria for ILI. Subsequently, results of any reported laboratory testing for identification of pathogens were included for cases meeting initial criteria for ILI. The severity of illness in participants with laboratory confirmed influenza illness were captured on a case report form rather than on an Adverse Event (AE) form.

  Day 0 after product administration through Day 280, up to Week 40

Secondary Outcomes (1)

• Antibody Response Following the Completion of Vaccination

  Baseline to 2 weeks after product administration

Study Arms (5)

Part A, Group 1 (1A-1B): FluMos-v1 (20 mcg)

EXPERIMENTAL

FluMos-v1 (20 mcg) administered intramuscularly (IM) by needle/syringe

Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)

Part A, Group 2 (2A-2B): FluMos-v1 (60 mcg)

EXPERIMENTAL

FluMos-v1 (60 mcg) administered intramuscularly (IM) by needle/syringe

Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)

Part A, Group 3 (3A-3B): Flucelvax (60 mcg)

ACTIVE COMPARATOR

Licensed QIV Flucelvax (60 mcg) administered intramuscularly (IM) by needle/syringe

Biological: Flucelvax

Part B, Group 4 (4A-4B): FluMos-v1 (100 mcg)

EXPERIMENTAL

FluMos-v1 (100 mcg) administered intramuscularly (IM) by needle/syringe

Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)

Part B, Group 5 (5A-5B): FluMos-v1 (100 mcg) + Adjuplex (20% v/v)

EXPERIMENTAL

FluMos-v1 (100 mcg) plus Adjuplex (20% v/v) administered intramuscularly (IM) by needle/syringe

Drug: VRC-GENADJ0110-AP-NV (Adjuplex); Drug: VRC-FLUMOS0111-00-VP (FluMos-v1)

Interventions

VRC-GENADJ0110-AP-NV (Adjuplex) DRUG

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. Adjuplex adjuvant was mixed with FluMos-v1 at 20% by volume in the pharmacy during product preparation for the vaccinations of Groups 5A-5B.

Also known as: Adjuplex

Part B, Group 5 (5A-5B): FluMos-v1 (100 mcg) + Adjuplex (20% v/v)

Flucelvax BIOLOGICAL

Flucelvax is an inactivated influenza vaccine licensed for the 2020-2021 season.

Part A, Group 3 (3A-3B): Flucelvax (60 mcg)

VRC-FLUMOS0111-00-VP (FluMos-v1) DRUG

FluMos-v1 investigational vaccine 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.

Also known as: FluMos-v1

Part A, Group 1 (1A-1B): FluMos-v1 (20 mcg); Part A, Group 2 (2A-2B): FluMos-v1 (60 mcg); Part B, Group 4 (4A-4B): FluMos-v1 (100 mcg); Part B, Group 5 (5A-5B): FluMos-v1 (100 mcg) + Adjuplex (20% v/v)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must have met all of the following criteria:
• Healthy adults between the ages of 18-50 years inclusive

You may not qualify if:

• Part A: Received at least one licensed influenza vaccine from 2016 through the 2019-2020 influenza season
• Part B: Received at least one licensed influenza vaccine from 2017 through the 2022-2023 influenza season
• Able and willing to complete the informed consent process
• Available for clinic visits for 40 weeks after enrollment and through an 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
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• 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.

  PMID: 21083388 BACKGROUND

• 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.

  PMID: 30742080 BACKGROUND

• Boyoglu-Barnum S, Ellis D, Gillespie RA, Hutchinson GB, Park YJ, Moin SM, Acton OJ, Ravichandran R, Murphy M, Pettie D, Matheson N, Carter L, Creanga A, Watson MJ, Kephart S, Ataca S, Vaile JR, Ueda G, Crank MC, Stewart L, Lee KK, Guttman M, Baker D, Mascola JR, Veesler D, Graham BS, King NP, Kanekiyo M. Quadrivalent influenza nanoparticle vaccines induce broad protection. Nature. 2021 Apr;592(7855):623-628. doi: 10.1038/s41586-021-03365-x. Epub 2021 Mar 24.

  PMID: 33762730 BACKGROUND

• Yang RS, Traver M, Barefoot N, Stephens T, Alabanza C, Manzella-Lapeira J, Zou G, Wolff J, Li Y, Resto M, Shadrick W, Yang Y, Ivleva VB, Tsybovsky Y, Carlton K, Brzostowski J, Gall JG, Lei QP. Mosaic quadrivalent influenza vaccine single nanoparticle characterization. Sci Rep. 2024 Feb 24;14(1):4534. doi: 10.1038/s41598-024-54876-2.

  PMID: 38402303 BACKGROUND

• Alabanza C, Gavrilov V, Scott T, Yang RS, Gowetski DB, Gall JG, Paula Lei Q. Quantitation of strain-specific hemagglutinin trimers in mosaic quadrivalent influenza nanoparticle vaccine by ELISA. Vaccine. 2023 Aug 7;41(35):5201-5210. doi: 10.1016/j.vaccine.2023.07.009. Epub 2023 Jul 12.

  PMID: 37451877 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Influenza, Human; Virus Diseases

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: VRC Clinical Trials Program Leadership
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

ctpleadership@mail.nih.gov

301-451-8715

Study Officials

• Lesia Dropulic, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Dose Escalation

Study Record Dates

• First Submitted: May 20, 2021
• First Posted: May 21, 2021
• Study Start: May 24, 2021
• Primary Completion: January 25, 2024
• Study Completion: January 25, 2024
• Last Updated: April 27, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)