Trial to Evaluate the Immunogenicity of Dose Reduction Strategies of the MVA-BN Monkeypox Vaccine

NCT05512949 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 22-0020A
• Study Type: interventional
• Target: 229
• Locations: 1 country
• Sites: 8

Brief Summary

This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical trial that will evaluate two intradermal (ID) regimens for Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine compared to the standard subcutaneous (SC) regimen in healthy, vaccinia-naïve adults 18 to 50 years of age, inclusive. At least 210 participants will be enrolled and randomized to one of three study arms. The two dose sparing strategies include one-fifth (2 x 10\^7) and one-tenth (1 x 10\^7) of the standard dose of MVA-BN administered ID on Day 1 and 29 (Arm 1 and 2, respectively). The comparator arm (Arm 3) will be the 2-dose standard (1 x 10\^8) MVA-BN SC regimen. The study will enroll a 1:1:1 randomization allocation. Participants will not be stratified by clinical trial site, demographic characteristics or human immunodeficiency virus (HIV) infection status; however, these data will be collected during screening and enrollment. Each participant may be screened either in a separate visit in the 7 days prior to Day 1 or on Day 1. The primary hypothesis involves a two-step hierarchical process. The study will first test non-inferiority of the 2 x 10\^7 ID regimen relative to 1 x 10\^8 SC (standard dose regimen). If the 2 x 10\^7 ID regimen is non-inferior to the standard dose regimen, hypothesis testing will proceed to test non-inferiority of the 1 x 10\^7 ID regimen relative to the standard dose regimen. The primary objectives are: 1) to determine if peak humoral immune responses following an ID regimen of 2 x 10\^7 50% Tissue Culture Infectious Dose (TCID50) MVA-BN are non-inferior to the licensed regimen of 1 x 10\^8 MVA-BN administered SC; 2) to determine if peak humoral immune responses following an ID regimen of 1 x 10\^7 TCID50 MVA-BN are non-inferior to the licensed regimen of 1 x 10\^8 MVA-BN administered SC.

Conditions

Monkeypox

Keywords

Dose Reduction; Immunogenicity; JYNNEOS; Monkeypox; MVA-BN; Open-Label; Randomized; Vaccine

Outcome Measures

Primary Outcomes (1)

• Vaccinia Virus Specific Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at Day 43

  Venous blood was collected at Study Day 43 and the serum was analyzed via the PRNT assay to determine if GMT of the intradermal regimen of 2 x 10\^7 TCID50 MVA-BN and 1 x 10\^7 TCID50 MVA- BN were non-inferior to that of the licensed regimen of 1 x 10\^8 TCID50 MVA-BN administered subcutaneously.

  Day 43

Secondary Outcomes (9)

• Individual Peak GMT Through Day 365

  Day 1 through Day 365

• Vaccinia Virus Specific PRNT GMT at Study Day 1, 15, 29, 43, 57, 90, 181, and 365

  Day 1 through Day 365

• Vaccinia Virus Specific PRNT Half-life (t ½)

  Day 43 through Day 365

• Number of Participants Reporting Solicited Systemic AEs Through 14 Days After Each Study Vaccination

  Day 1 through Day 43

• Number of Participants Reporting Solicited Local AEs Through 14 Days After Each Study Vaccination

  Day 1 through Day 43

Study Arms (3)

Arm 1

EXPERIMENTAL

0.1 mL of 2 x 10\^7 (50% Tissue Culture Infectious Dose (TCID50) JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN)) administered intradermally on Days 1 and 29. N=70

Biological: JYNNEOS

Arm 2

EXPERIMENTAL

0.05 mL of 1 x 10\^7 (50% Tissue Culture Infectious Dose (TCID50) JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN)) administered intradermally on Days 1 and 29. N=70

Biological: JYNNEOS

Arm 3

ACTIVE COMPARATOR

0.5 mL of 1 x 10\^8 (50% Tissue Culture Infectious Dose (TCID50) JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN)) administered subcutaneously on Days 1 and 29. N=70

Biological: JYNNEOS

Interventions

JYNNEOS BIOLOGICAL

JYNNEOS is FDA-approved and licensed as a smallpox and monkeypox vaccine in the United States. JYNNEOS is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus. Each 0.5 mL dose is formulated to contain 0.5 x 10\^8 to 3.95 x 10\^8 infectious units of MVA-BN live virus in 10 mM Tris (tromethamine), 140 mM sodium chloride at pH 7.7. Subcutaneous is administered in the deltoid region, intradermal is administered in the volar aspect (inner side) of the forearm.

Arm 1; Arm 2; Arm 3

Eligibility Criteria

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

You may qualify if:

• Individuals 18 - 50 years of age inclusive at the time of consent.
• Able to read the written informed consent, states willingness to comply with all study procedures, and is anticipated to be available for all study visits.
• Agreement to adhere to Lifestyle Considerations during the study.
• Females of reproductive potential who have sexual intercourse with males must agree to use highly effective contraception for at least 1 month prior to signing ICF and through Day 57.
• In good general health as evidenced by medical history, physical examination, and clinical judgement of the investigator to be in stable state of health.
• \*Participants with pre-existing stable chronic medical conditions defined as conditions not requiring significant change in therapy or hospitalization for worsening disease in the 4 weeks prior to enrollment can be included at the discretion of the investigator. This includes stable, well-controlled HIV positive individuals.
• If HIV infected individual, they must be on suppressive Antiretroviral therapy (ART) for at least 6 months, report a cluster of differentiation 4 (CD4) count of greater than 350 cells/uL and no Acquired Immune Deficiency Syndrome (AIDS)-defining illness in the last year.

You may not qualify if:

• Ever received a licensed or an investigational smallpox or monkeypox vaccine.
• \*This includes Dryvax, Acam2000, LC 16 m8, Modified Vaccinia Ankara (MVA)-based vaccine candidate or licensed vaccines, and Jynneos, Imvamune or Imvanex).
• Any history of monkeypox, cowpox, or vaccinia infection.
• Close contact of anyone known to have monkeypox in the 3 weeks prior to signing Informed Consent Form (ICF).
• Immunocompromised as determined by the investigator.
• Recent or current use of any immunosuppressing medications in the 4 weeks prior to signing ICF.
• Pregnant or breast feeding.
• Received or plans to receive a live vaccine in the 4 weeks prior to signing ICF and 4 weeks after each vaccination.
• Received or plans to receive any other vaccine in the 2 weeks prior to signing ICF through Day 43.
• Received experimental therapeutic agent or vaccine in the 3 months prior to signing ICF.
• Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products.
• \*\*\*This includes individuals with history of severe allergic reaction to gentamicin, ciprofloxacin, chicken or egg protein.
• Has tattoos, scars, or other marks which would, in the opinion of the investigator, interfere with assessment of the vaccination site.
• Has any medical disease or condition that, in the opinion of the participating site Principal Investigator (PI) or appropriate sub-investigator, precludes study participation.
• This includes acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial.

Sponsors & Collaborators

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

Study Sites (8)

University of California, San Diego (UCSD) - Antiviral Research Center (AVRC)

San Diego, California, 92103-8208, United States

Location

George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

The Hope Clinic of Emory University

Decatur, Georgia, 30030, United States

Location

NIH Clinical Research Center, Investigational Drug Management and Research Section

Bethesda, Maryland, 20892-1504, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115-6110, United States

Location

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3411, United States

Location

Related Publications (1)

• Frey SE, Baden LR, El Sahly HM, Davey RT, Rebolledo PA, Diemert DJ, Little SJ, Creech CB, Oikonomopoulou Z, Sherman AC, Whitaker JA, Rouphael NG, Desrosiers A, Martin TCS, Rolsma SL, Hoet B, Watanabe A, Jaunarajs A, Moss B, Tomashek KM, Lerner A, Beigel JH; DMID 22-0020 Study Group. Evaluation of the safety and immunogenicity of two fractional intradermal regimens of MVA-BN compared to standard dose vaccination. Vaccine. 2026 Jan 1;69:127959. doi: 10.1016/j.vaccine.2025.127959. Epub 2025 Nov 29.

  PMID: 41319397 DERIVED

MeSH Terms

Conditions

Mpox, Monkeypox

Interventions

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Results Point of Contact

• Title: Sharon E. Frey, M.D.
• Organization: St. Louis University

sharon.frey@health.slu.edu

314-977-5500

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2022
• First Posted: August 23, 2022
• Study Start: September 9, 2022
• Primary Completion: October 12, 2023
• Study Completion: February 24, 2025
• Last Updated: April 16, 2026
• Results First Posted: January 9, 2024

Record last verified: 2026-03-25

Locations

US (8)