Protocol Details

VRC 329: A Phase I Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Quadrivalent Influenza HA Stem Vaccine VRC-FLUMOS0122-00-VP (STEMos1) with and without ALFQ Adjuvant in Healthy Adults

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

002425-I

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 50 Years

Referral Letter Required

No

Population Exclusion(s)

Adults who are or may become unable to consent;
Children;
Pregnant Women;
Non-English Speaking

Keywords

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

Recruitment Keyword(s)

None

Condition(s)

Influenza Prevention;
Pandemic Influenza Prevention

Investigational Drug(s)

SteMos1
ALFQ Adjuvant

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: VRC-FLUMOS0122-00-VP (SteMos1) with and without Army Liposome Formulation containing saponin QS-21 (ALFQ) Adjuvant

Supporting Site

National Institute of Allergy and Infectious Diseases

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.

Eligibility

INCLUSION CRITERIA:

A participant must meet all of the following criteria:

-Healthy adults between the ages of 18-50 years, inclusive

-Based on history and physical examination, be in good general health and without a history of any of the conditions listed in the exclusion criteria

-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

-Alkaline phosphatase (ALP) < 1.1 x institutional ULN

-Total bilirubin within institutional normal range or accompanied by approval of the PI or designee

-Serum creatinine <= 1.1 x institutional ULN

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

Criteria applicable to women of childbearing potential:

-Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on the day of enrollment

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

-Women who are breast-feeding or planning to become pregnant during the study

A participant has received any of the following substances:

-Receipt of any licensed influenza vaccine or lab-confirmed influenza infection within 6 months prior to enrollment.

-Plan to or are required to receive the 2025-2026 or 2026-2027 licensed influenza vaccines

-Live attenuated vaccines within 4 weeks prior to enrollment

-Inactivated vaccines within 2 weeks prior to enrollment

-mRNA vaccines within 4 weeks prior to enrollment

-Receipt of the HA ferritin influenza vaccine VRC-FLUNPF081-00-VP alone or in prime-boost regimens with VRC-FLUDNA082-00-VP (HA-F A/Sing, DNA A/Sing, VRC 316).

-Receipt of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1, VRC 325)

-Receipt of the mosaic hexavalent influenza vaccine VRC-FLUMOS0116-00-VP (FluMos-v2, VRC 326)

-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

-Blood products within 16 weeks prior to enrollment

-Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study

-Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule

-Current anti-TB prophylaxis or therapy

Participant has a history of any of the following clinically significant conditions:

-Serious reactions to vaccines that preclude receipt of the study vaccinations as determined by the PI or designee

-Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema

-Asthma that is not well controlled

-Diabetes mellitus (type I or II), except for gestational diabetes

-Thyroid disease that is not well controlled

-Idiopathic urticaria within the past year

-Immune-mediated diseases, such as autoimmune or autoinflammatory diseases, or immunodeficiencies

-Hypertension that is not well controlled

-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

-Malignancy that is active or history of malignancy that is likely to recur during the period of the study

-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

-Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen

-Guillain-Barr(SqrRoot)(Copyright) Syndrome

-Any medical, social condition, occupational reason, or other reason that, in the judgment of the PI or designee, is a contraindication to protocol participation or impairs a participant's ability to give informed consent, including but not limited to clinically significant forms of infectious diseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, or heart disease.


Citations:

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; PMCID: PMC11192176.

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; PMCID: PMC8269962.

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; PMCID: PMC10619166.

Contacts:

Principal Investigator

Referral Contact

For more information:

Lesia K. Dropulic, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)



VRC Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center
National Institutes of Health (NIH)
Bethesda, MD 20892

(301) 451-8715
vaccines@nih.gov
VRC Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center
National Institutes of Health (NIH)
Bethesda, MD 20892

(301) 451-8715
vaccines@nih.gov

Clinical Trials Number:

NCT07111078
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