IMVAMUNE® Smallpox Vaccine in Adult Healthcare Personnel at Risk for Monkeypox in the Democratic Republic of the Congo

Study Overview
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Brief Summary
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Monkeypox is a febrile rash illness caused by the monkeypox virus. Its natural occurrence in the DRC puts healthcare and frontline workers at high risk of acquiring monkeypox virus infections that can prevent them from performing work duties, compromise the overall healthcare delivery in an already fragile system, and can result in death (case fatality estimates are approximately 10%). This is an open-label prospective cohort study in up to 1,600 eligible healthcare workers at risk of monkeypox infection through their daily work. The study will document monkeypox exposure and infection in participants while concurrently evaluating the immunogenicity and safety of the vaccine, IMVAMUNE® (also known as MVA-BN, JYNNEOS, IMVANEX), in healthcare personnel in the DRC. Participation in the study is voluntary and open to male and female healthcare personnel ages 18 years and older in Tshuapa Province in The Democratic Republic of Congo who are at risk of monkeypox virus infection through their daily work or laboratory personnel performing diagnostic testing for monkeypox virus.

Detailed Description
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Orthopoxvirus infections produce antibody responses that are cross-protective against other viruses within the genus. It is this property of orthopoxviruses that allows a vaccine for vaccinia virus against smallpox to be used to provide protection against monkeypox. Studies performed during and in the immediate aftermath of smallpox eradication demonstrated that smallpox vaccination (with a first generation vaccine) could confer protection against infection with monkeypox virus. Newer, third generation vaccines such as IMVAMUNE, an attenuated (replication deficient) strain of vaccinia virus may offer an alternative safer source of vaccine-derived protection. The clinical presentation of monkeypox infection is similar to smallpox, although it is less transmissible human-to-human than smallpox and less deadly (case fatality estimates for monkeypox are approximately 10%). Naturally-occurring human monkeypox is largely restricted to remote regions of the Congo Basin forest in Central Africa. This study is the first rigorous evaluation of IMVAMUNE in a region where natural Orthopoxvirus transmission occurs at appreciable and predictable rates. Healthcare and frontline workers in the DRC are currently at high risk of acquiring monkeypox virus infection that prevents them from performing work duties, compromises healthcare delivery in an already fragile system, and can result in death. This open-label prospective cohort study in up to 1,600 healthcare personnel at risk of monkeypox infection through their daily work will document monkeypox virus exposure and infection in vaccinated participants while concurrently evaluating the immunogenicity and safety of IMVAMUNE vaccine. Study participation is voluntary and open to male and female healthcare personnel ages 18 years and older in Tshuapa Province in the DRC. Participants will receive two subcutaneous doses of IMVAMUNE vaccine on days 0 and 28. A subset of study participants will receive a booster dose. Blood samples will be obtained on days 0, 14, 28, 42, 180, 365, 545, and 730 for immunogenicity analysis. After each vaccination participants will be observed for at least thirty minutes. They will maintain an adverse event diary to record systemic and local adverse events for 7 days after each immunization. They will also record exposure to the monkeypox virus in an exposure diary that is reviewed at each follow-up visit. The study will evaluate the proportion of participants who after being vaccinated 1) develop suspected or confirmed monkeypox infection, and 2) experience exposure to monkeypox virus. The study will also evaluate the safety and immunogenicity of IMVAMUNE.

Official Title
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An Open-Label Prospective Cohort Study of IMVAMUNE® Smallpox Vaccine in Adult Healthcare Personnel at Risk for Monkeypox in the Democratic Republic of the Congo

Conditions
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Monkeypox Virus Infection

Intervention / Treatment
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* Biological: IMVAMUNE (Liquid Formulation)
* Biological: IMVAMUNE (Lyophilized Formulation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and nonpregnant females (as indicated by a negative urine pregnancy test prior to first dose of vaccine) age 18 years and older. Healthcare personnel at risk of monkeypox infection working in the Tshuapa Province of DRC or laboratory personnel performing diagnostic testing for monkeypox at the time of enrollment Willing to adhere to infection control recommendations to the extent possible based on availability of resources. Able and willing to complete the informed consent process and study procedures (including blood sample collection, urine pregnancy test, and completion of adverse event diary and exposure forms). Available for all study visits. Exclusion Criteria: Any history of allergy or anaphylaxis to any prior vaccines, eggs, or aminoglycosides. Current pregnancy (a negative urine pregnancy test is required for women participants who self-report as not pregnant). Enrollment for such participants may be deferred to a later time at which this criteria can be met. Acute illness that is accompanied by an axillary temperature ≥37.2°C (99.0°F) at the time of vaccination. Enrollment for such participants may be deferred to a later time at which this criteria can be met. Known experimental research agents or other vaccine within 28 days (4 weeks) prior to vaccination. Enrollment for such participants may be deferred to a later time at which this criteria can be met. Any reason the PIs suspect that data collected from this person would be incomplete or of poor quality. Any condition that the PIs suspect may place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (Liquid Formulation)<br>Up to 1000 male and female healthcare personnel ages 18 years and older in Tshuapa Province in The Democratic Republic of Congo at risk for monkeypox will receive two doses of attenuated live virus smallpox vaccine (IMVAMUNE liquid formulation) administered on days 0 and 28 via subcutaneous injection (deltoid) (1 x 108 Tissue Culture Infectious Dose 50 [TCID50] per 0.5 mL). A subset of participants will receive a booster dose. | Biological: IMVAMUNE (Liquid Formulation)<br>* Two doses of attenuated live virus smallpox vaccine (IMVAMUNE liquid formulation) administered on days 0 and 28 via subcutaneous injection (deltoid) (1 x 108 Tissue Culture Infectious Dose 50 [TCID50] per 0.5 mL). A subset of participants will receive a booster dose.<br>* Other names: IMVANEX;|
| Experimental: Intervention (Lyophilized Formulation)<br>Up to 600 male and female healthcare personnel ages 18 years and older in Tshuapa Province in The Democratic Republic of Congo at risk for monkeypox will receive two doses of attenuated live virus smallpox vaccine (IMVAMUNE lyophilized formulation) administered on days 0 and 28 via subcutaneous injection (deltoid) (1 x 108 Tissue Culture Infectious Dose 50 [TCID50] per 0.5 mL). A subset of participants will receive a booster dose. | Biological: IMVAMUNE (Lyophilized Formulation)<br>* Two doses of attenuated live virus smallpox vaccine (IMVAMUNE lyophilized formulation) administered on days 0 and 28 via subcutaneous injection (deltoid) (1 x 108 Tissue Culture Infectious Dose 50 [TCID50] per 0.5 mL). A subset of participants will receive a booster dose.<br>* Other names: IMVANEX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who develop suspected or confirmed monkeypox virus infection following receipt of IMVAMUNE |  | 2 years following initial vaccination | 
| Proportion of participants who experience exposure to monkeypox virus following receipt of IMVAMUNE |  | 2 years following initial vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who have orthopoxvirus antibody responses on days 0, 14, 28, 42, 180, 365, 545, and 730 days after the receipt of the first dose of vaccine |  | 2 years following initial vaccination | 
| Distribution of geometric means (GMTs) on days 0, 14, 28, 42, 180, 365, 545, and 730 days after the receipt of the first dose of vaccine |  | 2 years following initial vaccination | 
| Adverse event and serious adverse event information |  | 2 years following initial vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Democratic Republic of the Congo, IMVAMUNE, Modified Vaccinia Ankara (MVA), Monkeypox, Orthopoxvirus, Vaccine, Vaccinia virus, JYNNEOS