Trial Outcomes & Findings for A Phase 2 Randomized Multisite Trial to Inform Public Health Strategies Involving the Use of MVA-BN Vaccine for Mpox (NCT NCT05740982)

Participants enrolled in 22-0020B, Stage 2, were adolescents ages 12 to 17 years, inclusive, and adults ages 18 to 50 years, inclusive, who were healthy, vaccinia-naïve, and met all eligibility criteria (N=450). They were recruited from the general population at the participating study sites. Participants were enrolled between 22MAR2023 and 20JUL2023.

For the 22-0020B primary immunogenicity analysis, adolescents were compared against a pooled group of adults enrolled in 22-0020B, Stage 2 (NCT05740982) and adults enrolled in 22-0020A, Stage 1 (NCT05512949) who received the same study product regimen. The 76 participants in the Adults (Stage 1) arm were not considered enrolled in 22-0020B, thus the total enrollment for 22-0020B was 450 participants (Adolescents + Adults (Stage 2)).

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

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.

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.

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).

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.

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.

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).

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.

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.

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.

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.

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).

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.

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.

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).

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.

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.