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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 4 | 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 adults ages 18-50 years on Days 1 and 29. N=135 |
|
| 5 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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. |
| 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 |
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Inclusion Criteria:
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.
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.
. 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.
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
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.
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:
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)
Any history of monkeypox, cowpox, or vaccinia infection.
Close contact of anyone known to have monkeypox in the 3 weeks prior to signing ICF
Immunocompromised as determined by the investigator
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.
Pregnant or breast feeding.
Received or plans to receive a live vaccine or any COVID-19 vaccine in the 4 weeks before or after each study vaccination.
Received or plans to receive any other vaccine in the one week before or after each study vaccination.
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 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.
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.
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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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's of Alabama Child Health Research Unit (CHRU) | Birmingham | Alabama | 35233-0011 | United States | ||
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| Label | URL |
|---|---|
| MPox Vaccination Study Survey for adolescent participants interested in enrolling at the University of Rochester Medical Center | View source |
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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)).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Adolescents | Adolescents ages 12-17 years administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. MVA-BN, also known as JYNNEOS, is FDA-approved and licensed as a smallpox and mpox 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 vaccination is administered in the deltoid region. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 23, 2024 | Mar 25, 2026 |
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| 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 |
| 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 \ | Days 29, 43, 210, and 394 |
| George Washington University Medical Faculty Associates |
| Washington D.C. |
| District of Columbia |
| 20037 |
| United States |
| Emory University School of Medicine | Atlanta | Georgia | 30322-1014 | United States |
| University of Maryland, School of Medicine, Center for Vaccine Development and Global Health | Baltimore | Maryland | 21201-1509 | United States |
| NIH Clinical Research Center, Investigational Drug Management and Research Section | Bethesda | Maryland | 20892-1504 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115-6110 | United States |
| Saint Louis University Center for Vaccine Development | St Louis | Missouri | 63104-1015 | United States |
| Washington University in St. Louis | St Louis | Missouri | 63110-1010 | United States |
| University of Rochester Medical Center | Rochester | New York | 14642-0001 | United States |
| Duke Vaccine and Trials Unit | Durham | North Carolina | 27703 | United States |
| Cincinnati Children's Hospital Medical Center Vaccine Research Center | Cincinnati | Ohio | 45229-3039 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19146 | United States |
| UPMC University Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37212 | United States |
| University of Texas Medical Branch | Galveston | Texas | 77555-0435 | United States |
| Baylor College of Medicine | Houston | Texas | 77030-3411 | United States |
| Kaiser Permanente Washington Health Research Institute | Seattle | Washington | 98101-1466 | United States |
| Ponce Medical School Foundation Inc., CAIMED Center | Ponce | 00716 | Puerto Rico |
| FG001 | Adults (Stage 2) | Adults ages 18-50 years (enrolled in Stage 2) administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. MVA-BN, also known as JYNNEOS, is FDA-approved and licensed as a smallpox and mpox 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 vaccination is administered in the deltoid region. |
| FG002 | Adults (Stage 1) | Adults ages 18-50 years (enrolled in Stage 1) administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. MVA-BN, also known as JYNNEOS, is FDA-approved and licensed as a smallpox and mpox 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 vaccination is administered in the deltoid region. |
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| ID | Title | Description |
|---|---|---|
| BG000 | Adolescents | Adolescents ages 12-17 years administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. |
| BG001 | Adults (Stage 2) | Adults ages 18-50 years (enrolled in Stage 2) administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. |
| BG002 | Adults (Stage 1) | Adults ages 18-50 years (enrolled in Stage 1) administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants | No |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | Participants |
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| HIV Status | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | The modified intent-to-treat (mITT) population includes all participants who received at least one dose of vaccine and contributed both pre- and at least one post-vaccination venous blood sample for immunogenicity testing for which valid results were reported. Participants are analyzed according to the study product that they received. | Posted | Geometric Mean | 95% Confidence Interval | titer | Day 43 |
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| Primary | 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. | Posted | Count of Participants | Participants | Day 1 through Day 36 |
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| Primary | 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). | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 57 |
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| Primary | 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. | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 210 |
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| Primary | 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. | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 210 |
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| Primary | 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). | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 394 |
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| Primary | 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. | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 394 |
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| Secondary | 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. | The modified intent-to-treat (mITT) population includes all participants who received at least one dose of vaccine and contributed both pre- and at least one post-vaccination venous blood sample for immunogenicity testing for which valid results were reported. Participants are analyzed according to the study product that they received. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 1, 29, 210, and 394 |
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| Secondary | 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. | The modified intent-to-treat (mITT) population includes all participants who received at least one dose of vaccine and contributed both pre- and at least one post-vaccination venous blood sample for immunogenicity testing for which valid results were reported. Participants are analyzed according to the study product that they received. | Posted | Median | Full Range | days | Day 1 through Day 394 |
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| Secondary | 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. | Posted | Count of Participants | Participants | Day 1 through Day 36 |
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| Secondary | 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). | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 57 |
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| Secondary | 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. | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 210 |
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| Secondary | 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. | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 210 |
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| Secondary | 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). | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 394 |
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| Secondary | 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. | The Safety Analysis population includes all participants who received the first study vaccination. Participants are analyzed according to the study product that they received. | Posted | Count of Participants | Participants | Day 1 through Day 394 |
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| Secondary | 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 \ | The modified intent-to-treat (mITT) population includes all participants who received at least one dose of vaccine and contributed both pre- and at least one post-vaccination venous blood sample for immunogenicity testing for which valid results were reported. Participants are analyzed according to the study product that they received. | Posted | Number | 95% Confidence Interval | percentage of participants | Days 29, 43, 210, and 394 |
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Solicited events, including local and systemic AEs, were collected from the time of each study vaccination through 7 days after vaccination. Unsolicited, non-serious AEs were collected from Day 1 through Day 57. AESIs and MAAEs were collected from Day 1 through Day 210. SAEs were collected from Day 1 through end of study (Day 394).
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. Adverse Events for the Adults (Stage 1) arm are not displayed here because they are posted on ClinicalTrials.gov within the 22-0020A (NCT05512949) study record.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Adolescents | Adolescents ages 12-17 years administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. | 0 | 315 | 3 | 315 | 301 | 315 |
| EG001 | Adults (Stage 2) | Adults ages 18-50 years (enrolled in Stage 2) administered 0.5 mL of 1 x 10^8 TCID50 (50% tissue culture infectious dose) MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) subcutaneously on Days 1 and 29. | 0 | 135 | 2 | 135 | 128 | 135 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Major depression | Psychiatric disorders | MedDRA V27.0 | Non-systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA V27.0 | Non-systematic Assessment |
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| Infective myositis | Infections and infestations | MedDRA V27.0 | Non-systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA V27.0 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA V27.0 | Systematic Assessment |
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| Chills | General disorders | MedDRA V27.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA V27.0 | Systematic Assessment |
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| Injection Site Bruising | General disorders | MedDRA V27.0 | Non-systematic Assessment |
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| Injection Site Discolouration | General disorders | MedDRA V27.0 | Non-systematic Assessment |
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| Injection Site Erythema | General disorders | MedDRA V27.0 | Systematic Assessment |
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| Injection Site Induration | General disorders | MedDRA V27.0 | Systematic Assessment |
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| Injection Site Nodule | General disorders | MedDRA V27.0 | Non-systematic Assessment |
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| Injection Site Pain | General disorders | MedDRA V27.0 | Systematic Assessment |
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| Injection Site Pruritus | General disorders | MedDRA V27.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA V27.0 | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA V27.0 | Non-systematic Assessment |
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| Appetite Disorder | Metabolism and nutrition disorders | MedDRA V27.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA V27.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA V27.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA V27.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sharon E. Frey, M.D. | St. Louis University | 314-977-5500 | sharon.frey@health.slu.edu |
| Prot_004.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 5, 2024 | Mar 25, 2026 | SAP_005.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 11, 2023 | Jul 27, 2023 | ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D045908 | Mpox, Monkeypox |
| ID | Term |
|---|---|
| D011213 | Poxviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D018419 | Primate Diseases |
| D000820 | Animal Diseases |
| D012376 | Rodent Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C527606 | smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic |
Not provided
Not provided
Not provided
| 15-17 years |
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| 18 years and older |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Positive |
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| Non-Inferiority |
A non-inferiority test was performed with an unequal variance and two-sample t-test statistic to obtain GMT Ratio (defined as the ratio of Adolescents to Adults) and its corresponding 95% CIs and p-values. The humoral immune response is considered non-inferior in adolescents if the 95% confidence interval of the GMT Ratio is entirely above 0.67 (NI = -0.174 log10 scale). |
| This is a sensitivity analysis to Statistical Analysis 1, utilizing the same NI margin and methodology but comparing adolescents to adults from Stage 2 only. | t-test, 2 sided | Two-sample t-test with unequal variance, NI margin of 0.67, and two-sided type I error rate of 0.05. | <0.001 | Statistical significance is considered if p < 0.05. Not adjusted for multiple comparisons. | Geometric mean titer ratio (GMTR) | 1.59 | 2-Sided | 95 | 1.26 | 2.00 | Non-Inferiority | A non-inferiority test was performed with an unequal variance and two-sample t-test statistic to obtain GMT Ratio (defined as the ratio of Adolescents to Adults) and its corresponding 95% CIs and p-values. The humoral immune response is considered non-inferior in adolescents if the 95% confidence interval of the GMT Ratio is entirely above 0.67 (NI = -0.174 log10 scale). |
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