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

Study at a glance

From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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

ClinicalTrials.gov ID

NCT04896086

Acronym / sponsor ID

10000410

Conditions

Influenza, Seasonal Influenza

Keywords

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

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

63 participants (actual)

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health

Study start

24 May 2021 (actual)

Primary completion

25 Jan 2024 (actual)

Study completion

25 Jan 2024 (actual)

First posted

21 May 2021 (actual)

Results

Posted 4 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Prevention

Allocation

Non-randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

5

Model description

Dose Escalation

Who may qualify

Ages

18 to 50 years

Sex

All

Healthy volunteers

Accepted

Age groups

Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

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

   Time frame: 7 days after 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.

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

   Time frame: 7 days after 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.

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

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

   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.

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

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

   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.

5. Number of Participants With New Chronic Medical Conditions Following Product Administration

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

   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.

6. Number of Participants With Abnormal Laboratory Measures of Safety Following Product Administration

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

   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.

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

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

   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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Background: PubMed 21083388Lambert 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.
• Background: PubMed 30742080Kanekiyo 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.
• Background: PubMed 33762730Boyoglu-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.
• Background: PubMed 38402303Yang 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.
• Derived from this study: PubMed 37451877Alabanza 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.
• NIH Clinical Center Detailed Web PageLink provided by the sponsor.
• Individual participant dataSharing planned: No. Individual participant data (IPD) is not shared because it has limited value in a small phase 1 trial of healthy volunteers. We instead report non-IPD (aggregate) data as required in ClinicalTrials.gov.

Related trials for Influenza

• Enrolling by invitation

  Personalized Ventilator Settings for Patients on ECMO

  Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation

• RecruitingPhase 2

  BPL-1357 Against H1N1 Influenza Virus Challenge

  Influenza, Human

• Not yet recruitingPhase 1

  Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates

  Influenza

• RecruitingPhase 1

  pH1N1 Blinded Challenge Study

  Influenza

• RecruitingPhase 3

  A Study to Evaluate the Safety and Efficacy of MK-1406/CD388 for Prevention of Influenza (MK-1406-005/CD388.SQ.3.06)

  Influenza

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

1 site in 1 country: see every site and its status.