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.
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
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
450
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.
Children's of Alabama Child Health Research Unit (CHRU)
Birmingham, Alabama, United States
George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
Emory University School of Medicine
Atlanta, Georgia, United States
University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, United States
NIH Clinical Research Center, Investigational Drug Management and Research Section
Bethesda, Maryland, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Saint Louis University Center for Vaccine Development
St Louis, Missouri, United States
Washington University in St. Louis
St Louis, Missouri, United States
University of Rochester Medical Center
Rochester, New York, United States
Duke Vaccine and Trials Unit
Durham, North Carolina, United States
...and 8 more locations
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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: Day 1 through Day 394
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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
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Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Days 29, 43, 210, and 394