A Phase 2 Randomized Multisite Trial to Inform Public Health Strategies Involving the Use of MVA-BN Vaccine for Mpox

A Phase 2 Randomized, Open-Label, Multisite Trial to Inform Public Health Strategies Involving the Use of MVA-BN Vaccine for Mpox

This study is a Phase 2 open-label, non-placebo controlled, multi-site clinical trial that will evaluate the standard SC regimen in adolescents ages 12 through 17 years, inclusive, and compared to the standard subcutaneous regimen in adults ages 18 to 50, inclusive. Approximately 135 healthy, vaccinia-naïve adults will be enrolled in a comparator arm (Arm 4) and will be given the standard, licensed regimen of 1x10^8 TCID50 MVA-BN administered SC on Day 1 and 29. These adults (Arm 4) will be combined with the 76 healthy, vaccinia-naïve adults that received the standard SC regimen in Stage 1 (Arm 3). Together, this will be the comparator group for non-inferiority testing for the primary endpoint. Approximately 315 healthy, vaccinia-naïve adolescents will be enrolled and given 1x10^8 TCID50 MVA-BN administered SC on Days 1 and 29 (Arm 5). The study will have a set target enrollment of at least 25% adolescents ages 12 to 14 years, inclusive, to ensure that adequate numbers of younger adolescents are enrolled.

The primary objectives are 1.) to determine if peak (Day 43) humoral immune responses in adolescents ages 12 to 17 years following administration of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC are non-inferior to the response in adults ages 18 to 50 years who received the licensed 2-dose SC regimen of 1 x 10^8 TCID50 MVA-BN ; and 2.) to describe safety of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years.

Study Overview

• Status: Completed
• Conditions: Monkeypox
• Intervention / Treatment: Biological: JYNNEOS

Detailed Description

This study is a Phase 2 open-label, non-placebo controlled, multi-site clinical trial that will evaluate to inform public health decisions regarding the use of JYNNEOS for monkey pox prevention and mitigation of outbreaks. In stage 2 of the study, the standard subcutaneous (SC) regimen in adolescents ages 12 through 17 years, inclusive, and compared to the standard SC regimen in adults ages 18 to 50, inclusive. Approximately 135 healthy, vaccinia-naïve adults will be enrolled in a comparator arm (Arm 4) and will be given the standard, licensed regimen of 1x10^8 TCID50 MVA-BN administered SC on Day 1 and 29. These adults (Arm 4) will be combined with the 76 healthy, vaccinia-naïve adults that received the standard SC regimen in Stage 1 (Arm 3). Together, this will be the comparator group for non-inferiority testing for the primary endpoint. Approximately 315 healthy, vaccinia-naïve adolescents will be enrolled and given 1x10^8 TCID50 MVA-BN administered SC on Days 1 and 29 (Arm 5). The study will have a set target enrollment of at least 25% adolescents ages 12 to 14 years, inclusive, to ensure that adequate numbers of younger adolescents are enrolled.

The primary objectives are 1.) to determine if peak (Day 43) humoral immune responses in adolescents ages 12 to 17 years following administration of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC are non-inferior to the response in adults ages 18 to 50 years who received the licensed 2-dose SC regimen of 1 x 108 TCID50 MVA-BN; and 2.) to describe safety of a 2-dose 1 x 10^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years. The secondary objectives are 1) to evaluate humoral immune responses at baseline, prior to the second vaccination, and following receipt of the 2-dose SC regimen of 1 x 10^8 TCID50 MVA-BN in adolescents compared to adults on each study day; 2) to evaluate the kinetics of the humoral immune responses to the 2-dose SC regimen of 1 x 10^8 TCID50 MVA-BN in adolescents and adults through Day 365 after the second dose is administered; 3.) to compare relative safety and reactogenicity between adolescent and adult study arms; and 4.) to evaluate seroconversion between adolescent and adult study arms.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce Medical School Foundation Inc., CAIMED Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-0011
      • Children's of Alabama Child Health Research Unit (CHRU)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
  • Georgia
    • Atlanta, Georgia, United States, 30322-1014
      • Emory University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201-1509
      • University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
    • Bethesda, Maryland, United States, 20892-1504
      • NIH Clinical Research Center, Investigational Drug Management and Research Section
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-6110
      • Brigham and Women's Hospital
  • Missouri
    • St Louis, Missouri, United States, 63104-1015
      • Saint Louis University Center for Vaccine Development
    • St Louis, Missouri, United States, 63110-1010
      • Washington University in St. Louis
  • New York
    • Rochester, New York, United States, 14642-0001
      • University of Rochester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27703
      • Duke Vaccine and Trials Unit
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center Vaccine Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC University Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Galveston, Texas, United States, 77555-0435
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030-3411
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States, 98101-1466
      • Kaiser Permanente Washington Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Individuals 18 - 50 years of age inclusive at the time of consent; OR Adolescent ages 12 to 17 years inclusive at the time of consent.
2. Adult participant is 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; OR Parent(s)/Legal Authorized Representative (LAR)(s) of the participating adolescent is able to read and provides written informed permission and participating adolescent provides assent as appropriate for age or development and approved by IRB. Adolescent states willingness to comply with all study procedures and is anticipated to be available for all study visits.
3. . Adult participant is able to understand and agrees to adhere to Lifestyle Considerations during the study; OR Parent(s)/LAR(s) of the participating adolescent is able to understand and states willingness to comply with Lifestyle Considerations.

4. 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.

   NOTE: See MOP for definitions and list of acceptable and highly effective methods of contraception

5. In good general health as evidenced by medical history, physical examination, and clinical judgement of the investigator to be in stable state of health.

   NOTE: 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.

6. Individuals with HIV must be on suppressive ART for at least 6 months, report a CD4 count of greater than 350 cells/µL and no AIDS-defining illness in the last year.

Exclusion Criteria:

1. Ever received a licensed or an investigational smallpox or monkeypox vaccine.

   *This includes Dryvax, Acam2000, LC 16 m8, MVA-based vaccine candidate or licensed vaccines, and Jynneos, Imvamune or Imvanex)

2. Any history of monkeypox, cowpox, or vaccinia infection.
3. Close contact of anyone known to have monkeypox in the 3 weeks prior to signing ICF
4. Immunocompromised as determined by the investigator

5. Recent or current use of any immunosuppressing medications in the 4 weeks prior to signing ICF.

   **Topical, ophthalmic, inhaled, intranasal and intraarticular corticosteroids are acceptable, but receipt of >/=20 mg/day of prednisone or equivalent for >/=14 consecutive days in the 4 weeks prior to signing ICF is exclusionary.

6. Pregnant or breast feeding.
7. Received or plans to receive a live vaccine or any COVID-19 vaccine in the 4 weeks before or after each study vaccination.
8. Received or plans to receive any other vaccine in the one week before or after each study vaccination.
9. Received experimental therapeutic agent or vaccine in the 3 months prior to signing ICF.

10. 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.

11. Has tattoos, scars, or other marks which would, in the opinion of the investigator, interfere with assessment of the vaccination site.

12. Has any medical disease or condition that, in the opinion of the participating site 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.

13. Adolescent or adult participant has a history of myocarditis/pericarditis or a history of structural congenital heart defect/cardiac dysrhythmia that, in the opinion of the investigator, poses increased risk to the participant.
14. Adolescent or adult participant has a history of COVID-19 (with positive test for SARS-CoV-2) in the 4 weeks prior to receipt of the first study vaccination.

Note: This includes positive rapid antigen test, polymerase chain reaction (PCR) assay, or other nucleic acid amplification (NAAT) test including those performed by the participant at home.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 4; 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 adults ages 18-50 years on Days 1 and 29. N=135	Biological: JYNNEOS; 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.
Experimental: 5; 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 adolescents ages 12-17 years on Days 1 and 29. N=315	Biological: JYNNEOS; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccinia Virus Specific Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT)	Serum collected at Study Day 43 was assayed via PRNT to determine if humoral immune responses in adolescents ages 12 to 17 years are non-inferior to responses in adults after receipt of a 2-dose subcutaneous regimen of 1 x 10^8 MVA-BN. As the primary analysis, adolescents were compared against a pooled group of adults enrolled in Stage 2 and adults enrolled in Stage 1 who received the same study product regimen. As a sensitivity analysis, adolescents were compared against only adults enrolled in Stage 2.	Day 43
Number of Adolescents Reporting Solicited Adverse Events (AEs) by Severity	AEs solicited via memory aid provided to participants included fever, chills, nausea, headache, fatigue, change in appetite, myalgia, arthralgia, pain at the injection site, erythema/redness, induration/swelling, and pruritis at the injection site. Participants are considered reporting the AE if they reported mild or greater severity at any time through 7 days after each study vaccination (Days 1-8 for Dose 1 and Days 29-36 for Dose 2). The maximum severity reported by participants for each symptom is presented.	Day 1 through Day 36
Number of Adolescents Reporting Unsolicited Adverse Events (AEs) by Relationship to Study Product	Frequency of all unsolicited AEs from day of each study vaccination through 28 days after each vaccination (Day 1 through Day 29 for Dose 1 and Day 29 through Day 57 for Dose 2).	Day 1 through Day 57
Number of Adolescents Reporting Adverse Events of Special Interest (AESIs)	A protocol-specified adverse event of special interest (AESI) is defined as a case of myocarditis or pericarditis. All participants with signs and symptoms of myocarditis/pericarditis (e.g., chest pain, shortness of breath, palpitations, etc.) in whom myocarditis/pericarditis was excluded, or for whom an alternative diagnosis was made, were not be considered a suspect case and as such, not reported as an AESI. All other suspected cases of myocarditis or pericarditis were reported as an AESI and the case adjudicated using the Brighton Collaboration case definitions for myocarditis and pericarditis. The Brighton Collaboration case definitions were used to classify into possible, probable, or definite myocarditis or pericarditis cases.	Day 1 through Day 210
Number of Adolescents Reporting Medically Attended Adverse Events (MAAEs) Related to Study Product	A medically attended adverse event (MAAE) is defined as an AE with medically attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Adverse events identified at a routine study visit (e.g., abnormal vitals) will not be considered MAAEs.	Day 1 through Day 210
Number of Adolescents Reporting Serious Adverse Events (SAEs) by Relatedness to Study Product	SAEs included any untoward medical occurrence that resulted in death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. All SAEs were collected from Day 1 through end of study (Day 394).	Day 1 through Day 394
Number of Adolescents Who Withdrew From Study or Discontinued Vaccination	Participants could voluntarily withdraw their consent for study participation for any reason at any time. Primary reason for withdrawal was recorded and early termination visits were attempted. Participants who received the first vaccination could choose to discontinue receipt of study vaccine for any reason and could choose to remain in the study (i.e., not withdraw from study). In addition, a participant could be discontinued from receipt of the second vaccination. Discontinuation from vaccination did not mean automatic withdrawal from the study, and participants were monitored for safety and immunogenicity if the participant consented.	Day 1 through Day 394

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccinia Virus Specific Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT)	Serum collected at Days 1, 29, 210, and 394 was assayed via PRNT to evaluate humoral immune responses in adolescents ages 12 to 17 years compared to responses in adults after receipt of a 2-dose subcutaneous regimen of 1 x 10^8 MVA-BN.	Days 1, 29, 210, and 394
Vaccinia Virus Specific PRNT Half-life (t ½)	Half-life, defined as the time from expected peak response (Day 43) to 50% maximal response, was estimated using the first participant visit with titer results less than or equal to half the titer results at Day 43.	Day 1 through Day 394
Number of Participants Reporting Solicited Adverse Events (AEs) by Severity	AEs solicited via memory aid provided to participants included fever, chills, nausea, headache, fatigue, change in appetite, myalgia, arthralgia, pain at the injection site, erythema/redness, induration/swelling, and pruritis at the injection site. Participants are considered reporting the AE if they reported mild or greater severity at any time through 7 days after each study vaccination (Days 1-8 for Dose 1 and Days 29-36 for Dose 2). The maximum severity reported by participants for each symptom is presented.	Day 1 through Day 36
Number of Participants Reporting Unsolicited Adverse Events (AEs) by Relationship to Study Product	Frequency of all unsolicited AEs from day of each study vaccination through 28 days after each vaccination (Day 1 through Day 29 for Dose 1 and Day 29 through Day 57 for Dose 2).	Day 1 through Day 57
Number of Participants Reporting Adverse Events of Special Interest (AESIs)	A protocol-specified adverse event of special interest (AESI) is defined as a case of myocarditis or pericarditis. All participants with signs and symptoms of myocarditis/pericarditis (e.g., chest pain, shortness of breath, palpitations, etc.) in whom myocarditis/pericarditis was excluded, or for whom an alternative diagnosis was made, were not be considered a suspect case and as such, not reported as an AESI. All other suspected cases of myocarditis or pericarditis were reported as an AESI and the case adjudicated using the Brighton Collaboration case definitions for myocarditis and pericarditis. The Brighton Collaboration case definitions were used to classify into possible, probable, or definite myocarditis or pericarditis cases.	Day 1 through Day 210
Number of Participants Reporting Medically Attended Adverse Events (MAAEs) Related to Study Product	A medically attended adverse event (MAAE) is defined as an AE with medically attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Adverse events identified at a routine study visit (e.g., abnormal vitals) will not be considered MAAEs.	Day 1 through Day 210
Number of Participants Reporting Serious Adverse Events (SAEs) by Relatedness to Study Product	SAEs included any untoward medical occurrence that resulted in death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. All SAEs were collected from Day 1 through end of study (Day 394).	Day 1 through Day 394
Number of Participants Who Withdrew From Study or Discontinued Vaccination	Participants could voluntarily withdraw their consent for study participation for any reason at any time. Primary reason for withdrawal was recorded and early termination visits were attempted. Participants who received the first vaccination could choose to discontinue receipt of study vaccine for any reason and could choose to remain in the study (i.e., not withdraw from study). In addition, a participant could be discontinued from receipt of the second vaccination. Discontinuation from vaccination did not mean automatic withdrawal from the study, and participants were monitored for safety and immunogenicity if the participant consented.	Day 1 through Day 394
Percentage of Participants With Vaccinia Virus Specific PRNT Seroconversion	Seroconversion for the Vaccinia virus specific plaque reduction neutralization test (PRNT) is defined as any positive result if negative at baseline or a 2-fold increase in antibody titers above baseline if positive at baseline. A positive result is defined as antibody titers = lower limit of detection (LLOD), i.e., a detectable result, and a negative result is defined as antibody titers <LLOD.	Days 29, 43, 210, and 394

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• MPox Vaccination Study Survey for adolescent participants interested in enrolling at the University of Rochester Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Actual): August 28, 2024
• Study Completion (Actual): August 28, 2024

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: December 23, 2025

More Information

Terms related to this study

• Keywords: Adolescent; Vaccine; Adults; Pediatric; Open-label; Public Health; Phase 2; JYNNEOS; Monkeypox; MVA-BN; Humoral Immune Response; Mpox; Non-Randomized; Non-Inferiority Testing; Vaccinia Naive
• Additional Relevant MeSH Terms: Infections; Virus Diseases; Poxviridae Infections; DNA Virus Infections; Animal Diseases; Primate Diseases; Rodent Diseases; Mpox, Monkeypox; Anti-Infective Agents; Antiviral Agents; smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
• Other Study ID Numbers: 22-0020B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No