search
Back to results

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

Primary Purpose

Monkeypox Virus Infection

Status
Active
Phase
Phase 3
Locations
Congo, The Democratic Republic of the
Study Type
Interventional
Intervention
IMVAMUNE (Liquid Formulation)
IMVAMUNE (Lyophilized Formulation)
Sponsored by
Centers for Disease Control and Prevention
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Monkeypox Virus Infection focused on measuring Democratic Republic of the Congo, IMVAMUNE, Modified Vaccinia Ankara (MVA), Monkeypox, Orthopoxvirus, Vaccine, Vaccinia virus, JYNNEOS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Males and nonpregnant females (as indicated by a negative urine pregnancy test prior to first dose of vaccine) age 18 years and older.
  2. 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
  3. Willing to adhere to infection control recommendations to the extent possible based on availability of resources.
  4. 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).
  5. Available for all study visits.

Exclusion Criteria:

  1. Any history of allergy or anaphylaxis to any prior vaccines, eggs, or aminoglycosides.
  2. 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.
  3. 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.
  4. 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.
  5. Any reason the PIs suspect that data collected from this person would be incomplete or of poor quality.
  6. 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.

Sites / Locations

  • Tshuapa site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Intervention (Liquid Formulation)

Intervention (Lyophilized Formulation)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Proportion of participants who develop suspected or confirmed monkeypox virus infection following receipt of IMVAMUNE
Proportion of participants who experience exposure to monkeypox virus following receipt of IMVAMUNE

Secondary Outcome Measures

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
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
Adverse event and serious adverse event information

Full Information

First Posted
September 7, 2016
Last Updated
May 2, 2023
Sponsor
Centers for Disease Control and Prevention
Collaborators
Ministry of Public Health, Democratic Republic of the Congo, Kinshasa School of Public Health, Bavarian Nordic
search

1. Study Identification

Unique Protocol Identification Number
NCT02977715
Brief Title
IMVAMUNE® Smallpox Vaccine in Adult Healthcare Personnel at Risk for Monkeypox in the Democratic Republic of the Congo
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 23, 2017 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centers for Disease Control and Prevention
Collaborators
Ministry of Public Health, Democratic Republic of the Congo, Kinshasa School of Public Health, Bavarian Nordic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Monkeypox Virus Infection
Keywords
Democratic Republic of the Congo, IMVAMUNE, Modified Vaccinia Ankara (MVA), Monkeypox, Orthopoxvirus, Vaccine, Vaccinia virus, JYNNEOS

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1600 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention (Liquid Formulation)
Arm Type
Experimental
Arm Description
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.
Arm Title
Intervention (Lyophilized Formulation)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
IMVAMUNE (Liquid Formulation)
Other Intervention Name(s)
Modified Vaccinia Ankara (MVA), MVA-BN, JYNNEOS, IMVANEX
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMVAMUNE (Lyophilized Formulation)
Other Intervention Name(s)
Modified Vaccinia Ankara (MVA), MVA-BN, JYNNEOS, IMVANEX
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of participants who develop suspected or confirmed monkeypox virus infection following receipt of IMVAMUNE
Time Frame
2 years following initial vaccination
Title
Proportion of participants who experience exposure to monkeypox virus following receipt of IMVAMUNE
Time Frame
2 years following initial vaccination
Secondary Outcome Measure Information:
Title
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
Time Frame
2 years following initial vaccination
Title
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
Time Frame
2 years following initial vaccination
Title
Adverse event and serious adverse event information
Time Frame
2 years following initial vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brett Petersen, MD, MPH
Organizational Affiliation
Centers for Disease Control and Prevention
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kinkodi Didine Kaba, MD, PhD
Organizational Affiliation
DRC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tshuapa site
City
Boende
State/Province
Tshuapa
Country
Congo, The Democratic Republic of the

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30445121
Citation
Petersen BW, Kabamba J, McCollum AM, Lushima RS, Wemakoy EO, Muyembe Tamfum JJ, Nguete B, Hughes CM, Monroe BP, Reynolds MG. Vaccinating against monkeypox in the Democratic Republic of the Congo. Antiviral Res. 2019 Feb;162:171-177. doi: 10.1016/j.antiviral.2018.11.004. Epub 2018 Nov 14.
Results Reference
background
PubMed Identifier
36263798
Citation
Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Ahmad S, Hasan H, Ahmad Suhaimi NA, Albakri KA, Abedalbaset Alzyoud A, Kadir R, Mohamud R. Comprehensive literature review of monkeypox. Emerg Microbes Infect. 2022 Dec;11(1):2600-2631. doi: 10.1080/22221751.2022.2132882.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs