Cohort Events Monitoring (CEM) Study for the Assessment of Safety Profile of MVA-BN (Jynneos) Vaccine in Adult Personnel and Staff in the PALM-007 Study in Democratic Republic Of The Congo
Phase: PHASE4
Conditions: Monkeypox
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

COHORT EVENTS MONITORING (CEM) STUDY 
FOR THE ASSESSMENT OF SAFETY PROFILE OF 
MVA-BN (JYNNEOS) VACCINE IN ADULT 
PERSONNEL AND STAFF IN THE PALM-007 STUDY 
IN DEMOCRATIC REPUBLIC OF THE CONGO
Protocol v2.0, 07Oct2023
NCT05734508

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COHORT EVENTS MONITORING (CEM) STUDY FOR THE ASSESSMENT OF 
SAFETY PROFILE OF MVA-BN (JYNNEOS) VACCINE IN ADULT PERSONNEL 
AND STAFF IN THE PALM-007 STUDY IN DEMOCRATIC REPUBLIC OF THE 
CONGO
Abbreviated title: 
CEM-JYNNEOS 
Full Title: 
Cohort events monitoring (CEM) study for the assessment 
of safety profile of MVA-BN (Jynneos) vaccine in adult 
personnel and staff in the PALM-007 study in Democratic 
Republic Of The Congo 
Protocol number: 
PALM 008 
Version of protocol: 
Version 2.0 dated 07 Oct 2023 
Principal Investigator: 
Nsengi Ntamabyaliro, MD, MSc PhD 
Co-Principal Investigator: 
Aline Engo Biongo, MD 

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Table of contents 
1.
Background and rationale ................................................................................................................... 4 
Background .................................................................................................................................................. 4 
Potential benefits ......................................................................................................................................... 4 
Possible risks ................................................................................................................................................ 5 
2.
Objectives of the study ........................................................................................................................ 5 
2.1. 
General objective .......................................................................................................................... 5 
2.2. 
Specific objectives ........................................................................................................................ 5 
3.
Methods ................................................................................................................................................ 5 
3.1. 
Study design ................................................................................................................................. 5 
3.2. 
Study population .......................................................................................................................... 6 
3.2.1. 
Inclusion criteria ....................................................................................................................... 6 
3.2.2. 
Exclusion criteria ...................................................................................................................... 6 
3.4 Withdrawal from the study ............................................................................................................... 6 
3.5 Pregnant and breastfeeding women ............................................................................................... 7 
3.3. 
Study sites .................................................................................................................................... 7 
4.
Study flow ............................................................................................................................................. 7 
4.1. 
Screening and enrollment of participants .................................................................................. 7 
4.2. 
Follow-up of participants ............................................................................................................ 8 
4.3. 
Safety assessment ........................................................................................................................ 9 
4.3.1. 
Definitions ................................................................................................................................. 9 
4.3.2. 
Severity Grading ..................................................................................................................... 10 
4.3.3. 
Recording and reporting adverse events ............................................................................. 10 
5.
Investigational product (IP) description ........................................................................................... 11 
6.
Ethical consideration .......................................................................................................................... 11 
Informed Consent Process ..................................................................................................................... 12 
Consent Procedures and Documentation ........................................................................................ 12 
7.
Data Management and Monitoring ................................................................................................... 13 
Data Management Responsibilities .................................................................................................. 13 
Data Capture Methods ....................................................................................................................... 13 
Record Retention ................................................................................................................................ 13 
Site Monitoring Plan .......................................................................................................................... 13 
Confidentiality and Privacy: ................................................................................................................... 14 
8.
Statistical Considerations .................................................................................................................. 15 
9.
Schedule of activities ......................................................................................................................... 16 
10. Abbreviations ..................................................................................................................................... 17 

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11. References........................................................................................................................................... 18 
List of Tables 
Table 9.1 Schedule of Activities ...................................................................................................................... 16 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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1. Background and rationale 
Background 
Monkeypox is a viral zoonotic infection meaning that it can spread from animals to humans. 
It can also spread through human-to-human contact. The PALM-007 study will be conducted 
in the Democratic Republic of the Congo (DRC) to assess the efficacy and safety of 
tecovirimat, a potential treatment drug for Monkeypox in hospitalized patients. Given their 
proximity to the patient, PALM-007 personnel and staff associated with the study are at high 
risk of contracting Monkeypox disease. Therefore, there is a need to protect them by 
vaccination as recommended by the World Health Organization (WHO). (1)  
The MVA-BN vaccine, which can be given subcutaneously (2), has been approved by 
regulatory authorities in the USA (JYNNEOS)(3) and Europe (Imvanex)(4) for prevention of 
Monkeypox infection.. 
The Ministry of Health, having given temporary authorization for the use of this vaccine, 
believes it is important to monitor vaccinated individuals and thus determine the safety 
profile of this vaccine in the Congolese adult population. This vaccination will therefore be 
accompanied by a safety follow-up of all participants. 
Potential benefits 
Data available to date suggest that MVA-BN vaccine is highly effective in the prevention of 
Monkeypox and has been approved by the US Food and Drug Administration (FDA) and 
European Medicines Agency (EMA). 
A study on macaques has shown that 2 doses of MVA-BN induce 100% protection against 
a lethal challenge of aerosolized Monkeypox virus(5). A separate study in cynomolgus 
macaques demonstrated no significant difference between levels of neutralizing antibodies 
in animals vaccinated with ACAM2000 (a second-generation smallpox vaccine) and those 
vaccinated with 2 doses of MVA-BM(6). Preclinical studies and Phase I/II clinical trials of 
MVA-BN have suggested that 2 doses of vaccine are immunogenic generating antibody 
levels considered protective against smallpox and, by extrapolation, against monkeypox as 
well.(7)  

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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In the DRC, the MVA-BN vaccine has received temporary authorization for use. Therefore, 
PALM-007 staff may benefit from participation in this study, in the form of protection against 
Monkeypox infection. 
Possible risks 
Like any active product, the MVA-BN vaccine can cause side effects. Data from several clinical 
trials show that MVA-BN has a favorable adverse effect profile. There are, however, some 
common mild adverse events (AEs), such as local site reactions and flu-like symptoms. Other 
local side effects may include erythema, pain, edema, pruritus, hyperpigmentation and 
induration. Other systemic side effects can include fatigue, headache, myalgias, nausea, chills, 
fever. The frequency of AEs, especially local site reactions, in people who have never been 
vaccinated against smallpox and vaccinated for the first time (with MVA-BN) does not appear 
to be significantly higher than the frequency of AEs in those who have previously been 
vaccinated. 
2. Objectives of the study 
2.1. 
General objective 
 
The overall objective of this observational study is to monitor and assess the safety profile 
of the MVA-BN vaccine among staff and study personnel of the PALM-007 study in DRC.  
2.2. 
Specific objectives 
 
The specific objectives are as follows: 
- 
Estimate the incidence of serious adverse events (SAEs) in all individuals vaccinated 
with the MVA-BN vaccine 
- 
Estimate the incidence of AEs after each dose of MVA-BN vaccine. 
3. Methods 
3.1. 
Study design 
This is a study of the safety of the MVA-BN vaccine through a one-arm prospective 
observational cohort study that will be conducted under the coordination of the National 
Pharmacovigilance Center of the DRC. After informed consent is obtained, study participants 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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will receive two doses of vaccine and will be actively followed up to the 28th days after their 
last dose of MVA-BN vaccine. 
3.2. 
Study population 
Participants 18 years and older will be recruited from personnel of the PALM-007 
Monkeypox study and staff associated with the study in the DRC. Participation in the study 
will be voluntary and up to 1000 participants may be enrolled at the PALM-007 study sites 
or in Kinshasa. 
3.2.1. Inclusion criteria 
- 
 Provides written informed consent 
- 
18 years of age or older  
- 
At high risk for Monkeypox infections 
- 
Personnel and staff associated with the PALM 007-Monkeypox study sites in the DRC  
- 
Willingness and ability to communicate AEs to study personnel.  
3.2.2. Exclusion criteria 
• Allergy to MVA-BN or any of its components 
• Pregnant or breastfeeding women 
• Fever (axillary temperature ≥37.5°celsius) 
• People who have already received the MVA-BN vaccine (in routine vaccination or 
another study involving this vaccine) 
• Participants who, in the judgement of the investigator, will be at significantly 
increased risk as a result of participation in the study 
• Individuals with any condition or circumstance that would render them unable to 
comply with study procedures (e.g., not reachable by phone) 
3.4 Withdrawal from the study 
Participants will have the right to withdraw from the study for any reason at any time. This 
will not affect their staff position on the PALM-007 study. People who have had a serious 
allergic reaction to the first dose of MVA-BN will not receive a second study dose but will be 
followed t as described in section 4.2. If participants had a previous serious allergic reaction 
to any of the components of MVA-BN prior to joining this study, they may be at increased 
risk of serious allergic reactions. Therefore, these participants will be excluded from the 
study. 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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If a participant develops monkeypox infection, he/she will be withdrawn from the study and 
will receive the best treatment available for this disease. If this occurs between the first and 
second dose of vaccine, the participant will not receive the second dose. 
 If a participant decides to withdraw from the study, no further data will be collected about 
him/her. However, data collected up to the time of withdrawal will be used in analyses. 
3.5 Pregnant and breastfeeding women 
Available data on the risk of MVA-BN (JYNNEOS) vaccine on embryo-fetal and postnatal 
development is insufficient; therefore, pregnant and breastfeeding women will be excluded 
from the study. A pregnancy test will be performed at screening and on Day 28 for all women 
of childbearing potential. If a woman becomes pregnant following receipt of the vaccine, her 
pregnancy will be monitored. She will be followed up for the full duration of the pregnancy. 
She will follow antenatal visits in the health facilities and the schedule recommended by the 
national policy. She will be requested to communicate to the study staff all AEs for 
assessment and reporting purposes. The outcome and the pregnancy will be assessed: the 
newborn will be examined, and all malformation/birth defect reported as serious adverse 
event. 
3.3. 
Study sites 
The study will be conducted at all sites of the PALM-007 study and in Kinshasa, at the 
National Institute of Biomedical Research (INRB). Participation in the study will be offered to 
the personnel and staff of the DRC PALM-007 study. 
4. Study flow  
4.1. 
Screening and enrollment of participants 
 
All personnel and staff of the PALM-007 study will be offered the opportunity to participate 
in the study by reviewing and signing the informed consent. After signing informed consent, 
participants will be examined. The following parameters will be assessed: 
• 
Anthropometric measurements (weight, height) 
• 
Vital signs: temperature (axillary), blood pressure, heart rate and respiratory rate 
• 
Medical history, including history of orthopox virus disease, vaccination, current 
co-morbidities and medication(s) 
• 
Physical examination 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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• 
Pregnancy test will be done for all women of childbearing potential. 
If a participant has met all eligibility criteria, they will be enrolled and will receive the vaccine 
as specified below. Participants who are excluded because of fever can be rescreened and 
included after resolution of the fever and its cause. 
Enrolled participants will receive the MVA-BN vaccine by subcutaneous injection of 0.5 mL 
in the shoulder (left or right). Care must be taken to hold the skin well between 3 fingers 
and insert the needle at an angle of approximately 45°. 
The first dose will be administered at the time of enrollment and the second dose 28 days 
later.  
After each vaccination the participant will remain under observation for 30 minutes. All AEs 
occurring during this period of observation, will be recorded, and reported to the National 
Center for Pharmacovigilance and to the ethics committee according to Congolese 
regulations. 
4.2. 
Follow-up of participants 
 
Participants will be followed until 28 days after the second dose of vaccine. Follow-up visit 
will be done either in person at INRB (in Kinshasa) and at the Monkeypox treatment centers 
in the PALM-007 study or by phone calls on Day 3, Day 14, and Day 28 post each 
vaccination. Study participants will be provided with contact information of vaccine research 
staff and have the right to contact the research team either directly or by phone if they have 
any questions about post-vaccination reactions they may be experiencing or if they are 
concerned. There is a window of +/- one day for each visit except the day of the second 
dose which can be done on day 28 after the first dose with a window of +7 days. This second 
dose must not be given before day 28. During each visit, participants will be asked to report 
to the research team AEs via open-ended questions. All SAEs will be followed-up. SAEs that 
have not resolved by the end of the per-protocol follow-up period for the subject (Day 28 
after second dose) are to be followed until final outcome is known (to the degree permitted 
by the IRB-approved informed consent form). If it is not possible to obtain a final outcome 
for an SAE (e.g., the participant is lost to follow-up), the last known status and the reason a 
final outcome could not be obtained will be recorded by the investigator on an SAE report 
update and the CRF. 
On the day of administration of the second dose of vaccine, vital signs, and physical 
examination will be done to all participants and a pregnancy test will be done on all women 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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of childbearing potential prior to vaccine administration. If the pregnancy test is positive, the 
second dose will not be given, and the participant will be followed up as described in section 
3.5. Participants will be instructed to report any AEs that are experienced outside of the 
protocol defined follow up days. The reporting form of the national pharmacovigilance 
system of the DRC will be used for reporting. The research team will complete the notification 
form which will be sent to the National Pharmacovigilance Center (CNPV) by e-mail (scanned 
copies). 
4.3. 
Safety assessment 
4.3.1. Definitions 
Adverse event 
An AE is any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (e.g., abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not 
considered related to the research. 
Adverse drug reaction 
All noxious and unintended responses to a medicinal product. The phrase "responses to a 
“medicinal products" means that a causal relationship between the medicinal product and 
the adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled 
out. 
Unexpected adverse event 
Unexpected adverse event is an event whose nature, severity or outcome is not consistent 
with the applicable product information (investigator’s brochure or package insert)  
Serious adverse event 
A serious adverse event is any untoward medical occurrence that: 
• results in death, 
• is life-threatening (places the subject at immediate risk of death from the event as it 
occurred), 
• requires inpatient hospitalization or prolongation of existing hospitalization, 
• results in persistent or significant disability/incapacity, 
• is a congenital anomaly/birth defect or,  

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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• is a medically important event. 
NOTE: Medical and scientific judgment should be exercised. Events that significantly 
jeopardize the subject and/or require intervention to prevent one of the SAE 
outcomes listed above are generally considered medically important and are thus 
SAEs. 
4.3.2. Severity Grading 
The severity of each AE will be graded according to the “Common Terminology Criteria for 
Adverse Events (CTCAE)” (v 5.0) which can be found at: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_
reference_5x7.pdf   
Events that are NOT gradable using the above specified table will be graded as follows: 
• Mild = grade 1 
• Moderate = grade 2 
• Severe = grade 3 
• Potentially life threatening = grade 4 
• Death = grade 5 
This grading will be recorded in the study participant file and the reporting form. 
4.3.3. Recording and reporting adverse events 
 
All AEs will be recorded in the participant's file and reported according to Congolese 
regulations. Serious and unexpected AEs which are fatal or are life threatening, must be 
reported as per the guidelines on Pharmacovigilance in DRC, i.e., as soon as the reporter 
(member of the research team) becomes aware of them but no later than 7 calendar days. 
Update notes may be provided within an additional period not exceeding 15 calendar days. 
The count of days begins when a reporter becomes aware of the adverse event and the 
minimum notification conditions are met. All other serious and unexpected AEs must be 
reported immediately, but within a period not exceeding 15 calendar days. All SAEs will be 
reported to the Ethics Committee, the national PV Centre and to the manufacturer. The study 
PI will be responsible for reporting all SAEs. The National PV Centre will send monthly reports 
to the regulatory authority of DRC, the ACOREP (Autorité Congolaise de Réglementation 
Pharmaceutique). 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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Non-serious AEs will be reported as line listing to the national PV center and include in the 
report to ACOREP. 
5. Investigational product (IP) description 
The MVA-BN vaccine will be supplied by Bavarian Nordic. It is indicated for the prevention 
of smallpox and Monkeypox disease. It is a live vaccine produced from the Modified Vaccinia 
Ankara-Bavarian Nordic strain (MVA-BN), an attenuated and non-replicating orthopox virus. 
MVA-BN is cultured in primary cells of chicken embryo fibroblasts, (CEF) suspended in a 
serum-free medium containing no material of direct animal origin, harvested from the CEF 
cells, purified and concentrated by multiple steps of Tangential Flow Filtration (TFF), 
including benzonase digestion. Each 0.5 mL dose is formulated to contain 0.5 x 108 to 3.95 
x 108 infectious units of live MVA-BN virus in 10 mM Tris (tromethamine), 140 mM sodium 
chloride pH 7.7. Each 0.5 mL dose may contain residual amounts of host cell DNA (≤ 20 
mcg), protein (≤ 500 mcg), benzonase (≤ 0.0025 mcg), gentamicin (≤ 0.163 mcg) and 
ciprofloxacin (≤ 0.005 mcg). MVA-BN is a sterile vaccine formulated without preservatives. 
The bottle caps are not made with natural rubber latex. This vaccine is stored at temperatures 
between -25°C and -15°C (-13°F and +5°F). The vaccine should be thawed and brought to 
room temperature before administration. When thawed, MVA-BN is a light yellow to pale 
white milky suspension. Once thawed, it can be stored at +2°C to +8°C (+36°F to +46°F) 
for 12 hours. It should not be re-frozen. 
For administration, the bottle should be gently shaken before use for at least 30 seconds.  
IP accountability 
The Study Pharmacist will be responsible for maintaining adequate documentation of vaccine 
accountability, including receipt of product, temperature monitoring, transport to sites and 
administration records. The documentation will link the participant’s identification number to 
the lot number of the vaccine administered to them. 
6. Ethical consideration 
The protocol, the informed consent form, and any document containing information to be 
provided to participants will be submitted for approval to the Ethics Committee of the School 
of Public Health of the University of Kinshasa. After approval by the Ethics Committee, the 
approval of the ACOREP will be required before the start of the study. 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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The study will be conducted according to the Declaration of Helsinki in its most recent 
version, Good Clinical Practice, the regulations in force in the DRC, as well as the American 
regulations governing the protection of human subjects such as 21 CFR 50 and the United 
States Office for Human Research Protections (OHRP) Informed Consent of Participants. 
Informed Consent Process 
Consent Procedures and Documentation 
All participants will be required to sign or fingerprint the approved informed consent form 
prior to any study-related procedures. 
Informed consent is a process where information is presented to enable persons to 
voluntarily decide whether or not to participate as a research participant. It is an ongoing 
conversation between the human research participant and the researchers which begins 
before consent is given and continues until the end of the participant’s involvement in the 
research. Discussions about the research will provide essential information about the study 
and include purpose, duration, experimental procedures, alternatives, risks, and benefits. 
Coercion and undue influence will be minimized by informing participants that their decision 
to join the study will not affect their position in the PALM 007 study. Participants will be 
given as much time as they need to read the consent form and ask questions of the 
investigators. Participants will also be given time to discuss their participation with family 
members, friends, and other healthcare providers. 
Informed consent will be obtained in person by a study team member authorized to obtain consent. 
The privacy of the participant will be maintained. The consenting investigator and participant will be 
located in a private area (e.g., clinic consult room). Participants will sign the informed consent 
document prior to any procedures being done specifically for the study. 
A copy of the informed consent document will be given to the participants for their records. The 
consenting investigator will document the signing of the consent form in the participant’s study 
record. The investigator will confirm that written legally effective consent has been obtained prior to 
initiating any study interventions. 
The rights and welfare of the participants will be protected by emphasizing to them that participation 
in this study is voluntary and participants may withdraw consent at any time throughout the course 
of the trial. If participants are not interested in participating or decide to withdraw from the 
study, their current position will not be affected. 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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7. Data Management and Monitoring 
Data Management Responsibilities 
The site investigator is responsible for assuring that the data collected is complete, accurate, and 
recorded in a timely manner. Source documentation (the point of initial recording of information) 
should support the data transferred to the electronic data system and, when possible, should be 
signed and dated by the person recording and/or reviewing the data. All data should be reviewed 
by the Investigator and co-signed as required. 
Data Capture Methods 
Study data collected from the participant at study sites will be recorded as paper or CRFs with 
subsequent transmission to the Data Coordinating Center. Data Coordinating Center personnel shall 
enter data into an electronic database. Corrections to electronic data systems will be tracked 
electronically (password protected and through an audit trail) with time, date, individual making the 
correction, and what was changed.  
Source Documents and Access to Source Data/Documents 
Source documents include all recordings of observations or notations of clinical activities, and all 
reports and records necessary for the evaluation and reconstruction of the clinical trial. Source 
documents may include, but are not limited to, the subject’s medical records, subject’s diaries, 
progress notes, pharmacy records, and any other similar reports or records of procedures performed 
during the subject’s participation in the study. Case report forms for this study will also be considered 
the source documents.  
Record Retention 
The protocol team is responsible for retaining all essential documents listed in the ICH Good Clinical 
Practice Guideline. All essential documentation for all study participants is to be maintained by the 
investigators in a secure storage facility for a minimum of 3 years per NIAID policies or per in-country 
local or federal regulatory requirements (whichever is longer). These records are also to be maintained 
in compliance with IRB/EC and local medical records retention requirements, whichever is longest. 
All stored records are to be kept confidential to the extent required by applicable laws in the 
jurisdiction in which they are stored. 
 
Site Monitoring Plan 
As per ICH-GCP 5.18, clinical protocols are required to be adequately monitored by the study 
sponsor. This study monitoring will be conducted according to the “NIAID Intramural Clinical 
Monitoring Guidelines.” If feasible, monitors under contract to the NIAID/Office of Clinical Research 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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Policy and Regulatory Operations (OCRPRO) or their designee may visit the clinical research site to 
monitor aspects of the study in accordance with the appropriate regulations and the approved 
protocol. The objectives of a monitoring visit would be: 1) to verify the existence of signed informed 
consent documents and documentation of the Informed Consent Form process for each monitored 
participant; 2) to verify the prompt and accurate recording of all monitored data points, and prompt 
reporting of all SAEs; 3) to compare data abstracts with individual participants’ records and source 
documents (participants’ charts, medical progress notes, test results and any other relevant original 
participant information); and 4) to help ensure investigators are in compliance with the protocol. The 
monitors also may inspect the clinical site regulatory files to ensure that regulatory requirements 
(Office for Human Research Protections [OHRP]) and applicable guidelines (ICH-GCP) are being 
followed. During the monitoring visits, the investigator (and/or designee) and other study personnel 
should be available to discuss the study progress and monitoring visit. 
Confidentiality and Privacy: 
All records will be kept confidential to the extent provided by local laws in the jurisdictions in which 
the study is conducted. Study monitors and other authorized individuals may inspect all documents 
and records required to be maintained by the investigator, including but not limited to, medical 
records. Records will be kept locked, and data will be coded. Any personally identifiable information 
maintained for this study will be kept on restricted-access computers and networks. Personally 
identifiable information will only be shared with individuals authorized to receive it under this 
protocol. Individuals not authorized to receive personally identifiable information will be provided 
with coded information only, as needed. Clinical information will not be released without written 
permission of the participant, except as necessary for monitoring by the IRB/EC, NIAID, local 
regulatory agencies, the pharmaceutical supporter, or other authorized individuals. 
The confidentiality of all participants will be protected in accordance with Good Clinical 
Practice. 
Compensation 
Participants will be vaccinated at the workplace; no compensation will be provided. However, 
if there is a need for an unscheduled visit, compensation of $5 US will be provided for 
transportation. During follow-up of pregnancies, and if necessary, the site may assist the 
pregnant women in the fees related to antenatal consultation and ultrasounds. A maximum 
of $5 may be given to the participant for each prenatal consultation and a maximum of $10 
for each ultrasound. 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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8. Statistical Considerations 
The study will vaccinate 1000 participants to estimate the following: 
1) The frequency and severity of solicited SAEs up to 14 days after each dose of the 
vaccination.  
2) The frequency and severity of AEs from the first vaccine dose to 28 days after the 
second vaccine dose.  
Statistical analysis 
The proportion of SAEs will be estimated along with 95% confidence intervals using the 
Clopper-Pearson method at: 
- 
14 days after the first vaccine administration, and 
- 
28 days after the vaccine boost. 
The proportion of AEs will be estimated along with 95% confidence intervals using the 
Clopper-Pearson method at: 
- 
 14 days after the first vaccine administration, and 
- 
28 days after the vaccine boost. 
The severity of events will be tabulated and analyzed for reporting. 
Sample size justification 
The sample size was determined according to the expected number of staff to be vaccinated, 
in addition to ensuring adequate precision of 95% confidence intervals of the estimates of 
the frequency of SAEs and AEs. With 1000 participants, the expected halfwidth of the 
confidence interval will not be greater than 0.05.  
 
 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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9. Schedule of activities  
Table 9.1 Schedule of Activities 
Evaluation/Procedure 
Screen 
Follow-up 
Visit 
1 
2 
3 
4 
4.1 
5 
6 
7 
Day 
0 
3±1b 
14±1b 
28±1b 
28+7 
3±1c 
14±1c 
28±1c 
Informed consent 
X 
 
 
 
 
 
 
 
Eligibility (inclusion/exclusion) 
assessment 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Medication review 
X 
X 
X 
X 
X 
X 
X 
X 
Weight and Height 
X 
 
 
 
 
 
 
 
Pregnancy test (serum or urine)* 
X 
 
 
 
X 
 
 
 
Vital Signs 
X 
 
 
 
X 
 
 
 
Physical examination 
X 
 
 
 
X 
 
 
 
Vaccination  
X 
 
 
 
X 
 
 
 
Assessment of AEs/SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
 
b Days after First dose of vaccine. 
C Days after second dose of vaccine 
* Pregnancy test for women of childbearing potential 
 
 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
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10. Abbreviations 
ACOREP 
Autorité Congolaise de Réglementation harmaceutique 
DNA 
DesoxyriboNucleic Acid 
CEF 
Chicken Embryo Fibroblasts 
EC 
Ethics Committee 
CEM 
Cohort Event Monitoring 
CNPV 
Centre National de Pharmacovigilance 
CRF 
Case report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
AE 
Adverse Event 
SAE 
Serious Adverse Event 
EMA 
European Medicines Agency 
ESP 
Ecole de Santé Publique 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
ICH 
International consil on harmonization 
INRB 
Institut National de Recherche Biomédicale 
IRB 
Institutional review board 
MVA-BN 
Modified Vaccinia Ankara-Bavarian Nordic  
NIAID 
National Institute of Allergy and Infectious Diseases  
OCPRO 
Office of Clinical Research Policy and Regulatory Operations 
OHRP 
Office for Human Research Protections  
WHO 
World health Organization 
PALM 
Pamoja Tulinde Maisha 
IP 
Investigational Product 
PV 
Pharmacovigilance 
DRC 
Democratic Republic of the Congo 
TFF 
Tangential Flow Filtration  
 
 
 

CEM safety of MVA-BN (JYNNEOS)                                                                               version 2.0  07Oct2023 
P a g e  18 | 18 
 
11. References 
1.  
WHO Smallpox Eradication programme. Vaccines and immunization for monkeypox. 
2022. p. 1–28.  
2.  
U.S. Food and Drug Administration. Package Insert JYNNEOS [Internet]. 2022 [cited 
2022 Oct 6]. p. 1–11. Available from: chrome-
extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.fda.gov/media/131078/
download 
3.  
BAVARIAN NORDIC ANNOUNCES U.S. FDA APPROVAL OF JYNNEOSTM (SMALLPOX 
AND MONKEYPOX VACCINE, LIVE, NON-REPLICATING) FOR PREVENTION OF 
SMALLPOX AND MONKEYPOX DISEASE IN ADULTS [Internet]. 2019 [cited 2022 Sep 
24]. Available from: https://www.drugs.com/newdrugs/fda-approves-jynneos-
smallpox-monkeypox-vaccine-live-non-replicating-prevention-smallpox-monkeypox-
5061.html 
4.  
EMA recommends approval of Spikevax for children aged 6 to 11 | European 
Medicines Agency [Internet]. [cited 2022 Aug 11]. Available from: 
https://www.ema.europa.eu/en/news/ema-recommends-approval-imvanex-
prevention-monkeypox-disease 
5.  
European Medicines Agency (EMA). Imvanex (live modified vaccinia Ankara virus) An 
overview of Imvanex and why it is authorised in the EU [Internet]. Vol. 44. 2022. p. 
1–2. Available from: https://www.ema.europa.eu/en/documents/overview/mylotarg-
epar-summary-public_en.pdf 
6.  
Hatch GJ, Graham VA, Bewley KR, Tree JA, Dennis M, Taylor I, et al. Assessment of 
the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized 
Monkeypox Virus in Cynomolgus Macaques. J Virol. 2013;87(14):7805–15.  
7.  
UK Health Security Agency. Recommendations for the use of pre and post exposure 
vaccination during a monkeypox incident. 2022;(June). Available from: 
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attach
ment_data/file/1080838/Recommendations-for-pre-and-post-exposure-vaccination-
during-a-monkeypox-incident-6-june-2022.pdf