Quadrivalent Influenza HA Stem Vaccine VRC-FLUMOS0122-00-VP (SteMos1) With and Without ALFQ Adjuvant in Healthy Adults

NCT07111078 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002425002425-I
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Influenza (flu) is a contagious respiratory illness caused by viruses. Flu symptoms can range from mild to severe, and the illness can be fatal. Vaccines help the body learn to prevent or fight infections such as flu. Some vaccines are combined with adjuvants. Adjuvants are special salts or fats that help vaccines work better. Researchers are looking for ways to make flu vaccines more effective. Objective: To test a new flu vaccine with and without a new adjuvant. Eligibility: Healthy adults aged 18 to 50. They must have had at least 1 flu vaccine since 2020. Design: Participants will have 12 clinic visits over 15 months. The vaccine is given as an injection into the muscle of the upper arm. Participants will be vaccinated during 2 visits spaced 4 months apart. Half will receive just the vaccine; half will receive the vaccine plus the adjuvant. They will be monitored for at least 30 minutes after each shot. Participants will keep a diary for 7 days after each shot. They check their temperature every day and record any symptoms. Participants will have 10 follow-up clinic visits plus 4 phone calls. They will have 4 to 10 tablespoons of blood drawn at each clinic visit. Fluid samples will be collected from their nose and mouth. They will be checked for any health changes. Participants may opt to undergo apheresis: Blood will be taken from the body through a needle inserted into a vein. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be returned to the body through a different needle.

Conditions

Influenza Prevention; Pandemic Influenza Prevention

Keywords

Dose-Escalation; INFLUENZA VIRUS; Immune Response; Respiratory Illness; Experimental Vaccine; Safety

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of 180 mg VRCFLUMOS0122-00-VP (SteMos1) vaccine with ALFQ adjuvant administered as a 2-dose regimen

  Assessed by:-Frequency and severity of solicited local reactogenicity symptoms reported for 7 days following each injection, through resolution of symptoms.-Frequency and severity of solicited systemic reactogenicity symptoms reported for 7 days following each injection, through the resolution of symptoms.-Frequency and grade of any unsolicited AEs, including abnormal safety laboratory measures, during the 28-day follow-up period post each product administration.-Frequency and grade of unsolicited AEs assessed as related to the product during the 28-day follow-up period after each product administration, -Frequency of adverse events leading to participant s withdrawal at any time throughout the study. -Frequency of SAEs, AESI, MAAEs and new chronic medical conditions that require ongoing medical management at any time throughout the study.

  Though 52 weeks after the second vaccine administration

• Safety and tolerability of 60 mg VRCFLUMOS0122-00-VP (SteMos1) vaccine with ALFQ adjuvant administered as a 2-dose regimen

  Assessed by:-Frequency and severity of solicited local reactogenicity symptoms reported for 7 days following each injection, through resolution of symptoms.-Frequency and severity of solicited systemic reactogenicity symptoms reported for 7 days following each injection, through the resolution of symptoms.-Frequency and grade of any unsolicited AEs, including abnormal safety laboratory measures, during the 28-day follow-up period post each product administration.-Frequency and grade of unsolicited AEs assessed as related to the product during the 28-day follow-up period after each product administration, -Frequency of adverse events leading to participant s withdrawal at any time throughout the study. -Frequency of SAEs, AESI, MAAEs and new chronic medical conditions that require ongoing medical management at any time throughout the study.

  Though 52 weeks after the second vaccine administration

• Safety and tolerability of 180 mg VRCFLUMOS0122-00-VP (SteMos1) vaccine without ALFQ adjuvant administered as a 2-dose regimen

  Assessed by:-Frequency and severity of solicited local reactogenicity symptoms reported for 7 days following each injection, through resolution of symptoms.-Frequency and severity of solicited systemic reactogenicity symptoms reported for 7 days following each injection, through the resolution of symptoms.-Frequency and grade of any unsolicited AEs, including abnormal safety laboratory measures, during the 28-day follow-up period post each product administration.-Frequency and grade of unsolicited AEs assessed as related to the product during the 28-day follow-up period after each product administration, -Frequency of adverse events leading to participant s withdrawal at any time throughout the study. -Frequency of SAEs, AESI, MAAEs and new chronic medical conditions that require ongoing medical management at any time throughout the study.

  Though 52 weeks after the second vaccine administration

• Safety and tolerability of 60 mg VRCFLUMOS0122-00-VP (SteMos1) vaccine without ALFQ adjuvant administered as a 2-dose regimen

  Assessed by:-Frequency and severity of solicited local reactogenicity symptoms reported for 7 days following each injection, through resolution of symptoms.-Frequency and severity of solicited systemic reactogenicity symptoms reported for 7 days following each injection, through the resolution of symptoms.-Frequency and grade of any unsolicited AEs, including abnormal safety laboratory measures, during the 28-day follow-up period post each product administration.-Frequency and grade of unsolicited AEs assessed as related to the product during the 28-day follow-up period after each product administration, -Frequency of adverse events leading to participant s withdrawal at any time throughout the study. -Frequency of SAEs, AESI, MAAEs and new chronic medical conditions that require ongoing medical management at any time throughout the study.

  Though 52 weeks after the second vaccine administration

Secondary Outcomes (4)

• Antibody responses to 180 mcg VRCFLUMOS0122-00-VP (SteMos1) vaccine administered with ALFQ as a 2-dose regimen

  Two weeks after each injection

• Antibody responses to 60 mcg VRCFLUMOS0122-00-VP (SteMos1) vaccine administered with ALFQ as a 2-dose regimen

  Two weeks after each injection

• Antibody responses to 180 mcg VRCFLUMOS0122-00-VP (SteMos1) administered without ALFQ as a 2-dose regimen

  Two weeks after each injection

• Antibody responses to 60 mg VRCFLUMOS0122-00-VP (SteMos1) vaccine administered without ALFQ as a 2-dose regimen

  Two weeks after each injection

Study Arms (5)

Group 1

EXPERIMENTAL

60 mcg of SteMos1 on Day 0 and Week 16

Biological: VRC-FLUMOS0122-00-VP

Group 2

EXPERIMENTAL

180 mcg of SteMos1 on Day 0 and Week 16

Biological: VRC-FLUMOS0122-00-VP

Group 3

EXPERIMENTAL

60 mcg of SteMos1 + 0.5 ml of ALFQ on Day 0 and Week 16

Biological: VRC-FLUMOS0122-00-VP; Other: ALFQ

Group 4

EXPERIMENTAL

180 mcg of SteMos1 + 0.5 ml of ALFQ on Day 0 and Week 16

Biological: VRC-FLUMOS0122-00-VP; Other: ALFQ

Group 5- optional

EXPERIMENTAL

SteMos1 \[dose TBD based on interim analysis of data from Groups 3-4\] + 0.5 ml of ALFQ on Day 0 and Week 16

Biological: VRC-FLUMOS0122-00-VP; Other: ALFQ

Interventions

VRC-FLUMOS0122-00-VP BIOLOGICAL

The VRC-FLUMOS0122-00-VP (SteMos1) is composed of de novo engineered pentamer assembled with de novo engineered trimeric domains to an icosahedral core, projecting 20 HA stabilized stem trimers from four influenza A strains representing both Group 1 (H2, H5) and Group 2 (H7, H10) viruses.

Group 1; Group 2; Group 3; Group 4; Group 5- optional

ALFQ OTHER

The ALFQ drug product is a sterile suspension that contains 240 mcg of monophosphoryl 3-deacyl Lipid A (3D-PHAD) and 120 mcg QS-21

Group 3; Group 4; Group 5- optional

Eligibility Criteria

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

You may qualify if:

• A participant must meet all of the following criteria:
• Healthy adults between the ages of 18-50 years, inclusive

You may not qualify if:

• Received at least one licensed influenza vaccine from the 2020-2021 influenza season through the 2024-2025 influenza season
• Able and willing to complete the informed consent process
• The ability to read and comprehend English as all consent and recruitment materials are in English.
• Available for clinic visits for 68 weeks after the first dose, including through the 2025-2026 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
• Agrees to not receive any licensed influenza vaccination during study participation due to potential confounding of study results
• Willing to have blood and mucosal samples collected, stored indefinitely, and used for research purposes.
• Laboratory Criteria within 56 days before enrollment:
• WBC and differential within institutional normal range or accompanied by approval of the site Principal Investigator (PI) or designee
• Total lymphocyte count \>= 800 cells/microliter
• Platelets = 125,000-400,000 cells/mircoliter
• Hemoglobin within institutional normal range or accompanied by approval of the PI or designee
• Alanine aminotransferase (ALT) \<= 1.25 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) \<= 1.25 x institutional ULN

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

RECRUITING

Related Publications (3)

• Ober Shepherd BL, Scott PT, Hutter JN, Lee C, McCauley MD, Guzman I, Bryant C, McGuire S, Kennedy J, Chen WH, Hajduczki A, Mdluli T, Valencia-Ruiz A, Amare MF, Matyas GR, Rao M, Rolland M, Mascola JR, De Rosa SC, McElrath MJ, Montefiori DC, Serebryannyy L, McDermott AB, Peel SA, Collins ND, Joyce MG, Robb ML, Michael NL, Vasan S, Modjarrad K; EID-030 Study Group. SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial. Lancet Microbe. 2024 Jun;5(6):e581-e593. doi: 10.1016/S2666-5247(23)00410-X. Epub 2024 May 15.

  PMID: 38761816 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

• Widge AT, Hofstetter AR, Houser KV, Awan SF, Chen GL, Burgos Florez MC, Berkowitz NM, Mendoza F, Hendel CS, Holman LA, Gordon IJ, Apte P, Liang CJ, Gaudinski MR, Coates EE, Strom L, Wycuff D, Vazquez S, Stein JA, Gall JG, Adams WC, Carlton K, Gillespie RA, Creanga A, Crank MC, Andrews SF, Castro M, Serebryannyy LA, Narpala SR, Hatcher C, Lin BC, O'Connell S, Freyn AW, Rosado VC, Nachbagauer R, Palese P, Kanekiyo M, McDermott AB, Koup RA, Dropulic LK, Graham BS, Mascola JR, Ledgerwood JE; VRC 321 study team. An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults. Sci Transl Med. 2023 Apr 19;15(692):eade4790. doi: 10.1126/scitranslmed.ade4790. Epub 2023 Apr 19.

  PMID: 37075129 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Lesia K Dropulic, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

VRC Clinic

CONTACT

(301) 451-8715; vaccines@nih.gov

Study Design

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

Study Record Dates

• First Submitted: August 7, 2025
• First Posted: August 8, 2025
• Study Start: August 27, 2025
• Primary Completion (Estimated): August 18, 2027
• Study Completion (Estimated): August 18, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04-17

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)