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

Phase 2

Active, not recruiting

• Conditions: Monkeypox
• Interventions: Biological: JYNNEOS

• Registration Number: NCT05740982
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-02-13
• Study First Submitted QC: 2023-02-13
• Study First Posted: 2023-02-23
• Study Start: 2023-03-22
• Primary Completion: 2024-08-28
• Status Verified: 2024-12
• Last Update Submitted: 2025-01-02
• Last Update Posted: 2025-01-06
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 450

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
5	JYNNEOS	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
4	JYNNEOS	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

Primary Outcome Measures

Name	Time	Method
Occurrence of Medically Attended Adverse Events (MAAE) in adolescents.	Day 1 through Day 210	Frequency and description of a 2-dose 1 x 10\^8 TCID50 MVA-BN regimen administered SC
Change from baseline in Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) in adolescents and adults.	Day 43	To determine if peak humoral immune responses in adolescents ages 12 to 17 years are non-inferior to adults after receipt of a 2-dose SC regimen of 1 x 10\^8 TCID50 MVA-BN.
Occurrence of Serious Adverse Events (SAEs) in adolescents.	Day 1 through Day 394	Frequency and relatedness of serious Adverse Events (SAE) of a 2-dose 1 x 10\^8 TCID50 MVA-BN regimen administered SC in for the duration of the study.
Occurrence of Adverse Events of Special Interest (AESI) in adolescents.	Day 1 through Day 210	Frequency and description of a 2-dose 1 x 10\^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years.
Occurrence of unsolicited Adverse Events (AE) in adolescents.	Day 1 through Day 57	Frequency severity, and relatedness of unsolicited Adverse Events after each vaccination of a 2-dose 1 x 10\^8 TCID50 MVA-BN regimen administered SC in for adolescents ages 12 to 17 years.
Occurrence of solicited Adverse Events (AE) in adolescents.	Day 1 through Day 36	Frequency and severity of solicited systemic and local Adverse Events for 7 days after each vaccination of a 2-dose 1 x 10\^8 TCID50 MVA-BN regimen administered SC in adolescents ages 12 to 17 years.
Occurrence of withdrawals and discontinuations of vaccination in adolescents.	Day 1 through Day 394	Frequency of occurrence within adolescents ages 12 to 17 years

Secondary Outcome Measures

Name	Time	Method
Occurrence of unsolicited Adverse Events (AE) in adolescents and adults	Day 1 through Day 57	Frequency, severity, and relatedness of unsolicited Adverse Events for 28 days after each vaccination; in study arms 1-5.
Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) half-life (t ½) in adolescents and adults.	Day 1 through Day 365	For adolescents ages 12 to 17 years compared to adults following receipt of the 2-dose SC regimen of 1 x 10\^8 TCID50 MVA-BN.
Occurrence of Medically Attended Events (MAAE) in adolescents and adults	Day 1 through Day 210	Frequency and relatedness in study arms 1-5
Occurrence of Adverse Events of Special Interest (AESI) in adolescents and adults	Day 1 through day 210	In study arms 1-5
Occurrence of Serious Adverse Events (SAE) in adolescents and adults	Day 1 through Day 394	Frequency and relatedness in study arms 1-5
Change from baseline in Vaccinia virus specific plaque reduction neutralizing antibody (PRNT) Geometric Mean Titers (GMT) in adolescents and adults	Day 1 through Day 394	Seroconversion in adolescent study arms 1-5
Frequency of withdrawals or discontinuation of vaccination in adolescents and adults	Day 1 through Day 181	Frequency in study arms 1-5
Occurrence of solicited Adverse Events (AE) for 7 days after each vaccination in adolescents and adults	Day 1 through Day 36	Frequency, severity, and relatedness of solicited systemic and local Adverse Events for 7 days after each vaccination in study arms 1-5.

Trial Locations

Locations (18)

Emory University School of Medicine; 🇺🇸 Atlanta, Georgia, United States

Kaiser Permanente Washington Health Research Institute; 🇺🇸 Seattle, Washington, United States

Duke Vaccine and Trials Unit; 🇺🇸 Durham, North Carolina, United States

Children's of Alabama Child Health Research Unit (CHRU); 🇺🇸 Birmingham, Alabama, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

George Washington University Medical Faculty Associates; 🇺🇸 Washington, District of Columbia, United States

NIH Clinical Research Center, Investigational Drug Management and Research Section; 🇺🇸 Bethesda, Maryland, United States

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health; 🇺🇸 Baltimore, Maryland, United States

Saint Louis University Center for Vaccine Development; 🇺🇸 Saint Louis, Missouri, United States

Washington University in St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Cincinnati Children's Hospital Medical Center Vaccine Research Center; 🇺🇸 Cincinnati, Ohio, United States

UPMC University Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas Medical Branch; 🇺🇸 Galveston, Texas, United States

Ponce Medical School Foundation Inc., CAIMED Center; 🇵🇷 Ponce, Puerto Rico

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States