<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02977715</url>
  </required_header>
  <id_info>
    <org_study_id>CDC-IRB-6859</org_study_id>
    <nct_id>NCT02977715</nct_id>
  </id_info>
  <brief_title>IMVAMUNE® Smallpox Vaccine in Adult Healthcare Personnel at Risk for Monkeypox in the Democratic Republic of the Congo</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Public Health, Democratic Republic of the Congo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kinshasa School of Public Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bavarian Nordic</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centers for Disease Control and Prevention</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Monkeypox is a febrile rash illness caused by the monkeypox virus. Its natural occurrence in&#xD;
      the DRC puts healthcare and frontline workers at high risk of acquiring monkeypox virus&#xD;
      infections that can prevent them from performing work duties, compromise the overall&#xD;
      healthcare delivery in an already fragile system, and can result in death (case fatality&#xD;
      estimates are approximately 10%).&#xD;
&#xD;
      This is an open-label prospective cohort study in up to 1,600 eligible healthcare workers at&#xD;
      risk of monkeypox infection through their daily work. The study will document monkeypox&#xD;
      exposure and infection in participants while concurrently evaluating the immunogenicity and&#xD;
      safety of the vaccine, IMVAMUNE® (also known as MVA-BN, JYNNEOS, IMVANEX), in healthcare&#xD;
      personnel in the DRC. Participation in the study is voluntary and open to male and female&#xD;
      healthcare personnel ages 18 years and older in Tshuapa Province in The Democratic Republic&#xD;
      of Congo who are at risk of monkeypox virus infection through their daily work or laboratory&#xD;
      personnel performing diagnostic testing for monkeypox virus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Orthopoxvirus infections produce antibody responses that are cross-protective against other&#xD;
      viruses within the genus. It is this property of orthopoxviruses that allows a vaccine for&#xD;
      vaccinia virus against smallpox to be used to provide protection against monkeypox. Studies&#xD;
      performed during and in the immediate aftermath of smallpox eradication demonstrated that&#xD;
      smallpox vaccination (with a first generation vaccine) could confer protection against&#xD;
      infection with monkeypox virus. Newer, third generation vaccines such as IMVAMUNE, an&#xD;
      attenuated (replication deficient) strain of vaccinia virus may offer an alternative safer&#xD;
      source of vaccine-derived protection.&#xD;
&#xD;
      The clinical presentation of monkeypox infection is similar to smallpox, although it is less&#xD;
      transmissible human-to-human than smallpox and less deadly (case fatality estimates for&#xD;
      monkeypox are approximately 10%). Naturally-occurring human monkeypox is largely restricted&#xD;
      to remote regions of the Congo Basin forest in Central Africa. This study is the first&#xD;
      rigorous evaluation of IMVAMUNE in a region where natural Orthopoxvirus transmission occurs&#xD;
      at appreciable and predictable rates. Healthcare and frontline workers in the DRC are&#xD;
      currently at high risk of acquiring monkeypox virus infection that prevents them from&#xD;
      performing work duties, compromises healthcare delivery in an already fragile system, and can&#xD;
      result in death.&#xD;
&#xD;
      This open-label prospective cohort study in up to 1,600 healthcare personnel at risk of&#xD;
      monkeypox infection through their daily work will document monkeypox virus exposure and&#xD;
      infection in vaccinated participants while concurrently evaluating the immunogenicity and&#xD;
      safety of IMVAMUNE vaccine. Study participation is voluntary and open to male and female&#xD;
      healthcare personnel ages 18 years and older in Tshuapa Province in the DRC. Participants&#xD;
      will receive two subcutaneous doses of IMVAMUNE vaccine on days 0 and 28. A subset of study&#xD;
      participants will receive a booster dose. Blood samples will be obtained on days 0, 14, 28,&#xD;
      42, 180, 365, 545, and 730 for immunogenicity analysis. After each vaccination participants&#xD;
      will be observed for at least thirty minutes. They will maintain an adverse event diary to&#xD;
      record systemic and local adverse events for 7 days after each immunization. They will also&#xD;
      record exposure to the monkeypox virus in an exposure diary that is reviewed at each&#xD;
      follow-up visit.&#xD;
&#xD;
      The study will evaluate the proportion of participants who after being vaccinated 1) develop&#xD;
      suspected or confirmed monkeypox infection, and 2) experience exposure to monkeypox virus.&#xD;
      The study will also evaluate the safety and immunogenicity of IMVAMUNE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 23, 2017</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of participants who develop suspected or confirmed monkeypox virus infection following receipt of IMVAMUNE</measure>
    <time_frame>2 years following initial vaccination</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of participants who experience exposure to monkeypox virus following receipt of IMVAMUNE</measure>
    <time_frame>2 years following initial vaccination</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>2 years following initial vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>2 years following initial vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event and serious adverse event information</measure>
    <time_frame>2 years following initial vaccination</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1600</enrollment>
  <condition>Monkeypox Virus Infection</condition>
  <arm_group>
    <arm_group_label>Intervention (Liquid Formulation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention (Lyophilized Formulation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IMVAMUNE (Liquid Formulation)</intervention_name>
    <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.</description>
    <arm_group_label>Intervention (Liquid Formulation)</arm_group_label>
    <other_name>Modified Vaccinia Ankara (MVA)</other_name>
    <other_name>MVA-BN</other_name>
    <other_name>JYNNEOS</other_name>
    <other_name>IMVANEX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IMVAMUNE (Lyophilized Formulation)</intervention_name>
    <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.</description>
    <arm_group_label>Intervention (Lyophilized Formulation)</arm_group_label>
    <other_name>Modified Vaccinia Ankara (MVA)</other_name>
    <other_name>MVA-BN</other_name>
    <other_name>JYNNEOS</other_name>
    <other_name>IMVANEX</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and nonpregnant females (as indicated by a negative urine pregnancy test prior&#xD;
             to first dose of vaccine) age 18 years and older.&#xD;
&#xD;
          2. Healthcare personnel at risk of monkeypox infection working in the Tshuapa Province of&#xD;
             DRC or laboratory personnel performing diagnostic testing for monkeypox at the time of&#xD;
             enrollment&#xD;
&#xD;
          3. Willing to adhere to infection control recommendations to the extent possible based on&#xD;
             availability of resources.&#xD;
&#xD;
          4. Able and willing to complete the informed consent process and study procedures&#xD;
             (including blood sample collection, urine pregnancy test, and completion of adverse&#xD;
             event diary and exposure forms).&#xD;
&#xD;
          5. Available for all study visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any history of allergy or anaphylaxis to any prior vaccines, eggs, or aminoglycosides.&#xD;
&#xD;
          2. Current pregnancy (a negative urine pregnancy test is required for women participants&#xD;
             who self-report as not pregnant). Enrollment for such participants may be deferred to&#xD;
             a later time at which this criteria can be met.&#xD;
&#xD;
          3. Acute illness that is accompanied by an axillary temperature ≥37.2°C (99.0°F) at the&#xD;
             time of vaccination. Enrollment for such participants may be deferred to a later time&#xD;
             at which this criteria can be met.&#xD;
&#xD;
          4. Known experimental research agents or other vaccine within 28 days (4 weeks) prior to&#xD;
             vaccination. Enrollment for such participants may be deferred to a later time at which&#xD;
             this criteria can be met.&#xD;
&#xD;
          5. Any reason the PIs suspect that data collected from this person would be incomplete or&#xD;
             of poor quality.&#xD;
&#xD;
          6. Any condition that the PIs suspect may place the participant at an unacceptable risk&#xD;
             of injury or render the participant unable to meet the requirements of the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brett Petersen, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centers for Disease Control and Prevention</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kinkodi Didine Kaba, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>DRC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tshuapa site</name>
      <address>
        <city>Boende</city>
        <state>Tshuapa</state>
        <country>Congo, The Democratic Republic of the</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Congo, The Democratic Republic of the</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>30445121</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 7, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Democratic Republic of the Congo</keyword>
  <keyword>IMVAMUNE</keyword>
  <keyword>Modified Vaccinia Ankara (MVA)</keyword>
  <keyword>Monkeypox</keyword>
  <keyword>Orthopoxvirus</keyword>
  <keyword>Vaccine</keyword>
  <keyword>Vaccinia virus</keyword>
  <keyword>JYNNEOS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Smallpox</mesh_term>
    <mesh_term>Monkeypox</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02977715
org study id: CDC-IRB-6859
nct id: NCT02977715
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Proportion of participants who develop suspected or confirmed monkeypox virus infection following receipt of IMVAMUNE
time frame: 2 years following initial vaccination
measure: Proportion of participants who experience exposure to monkeypox virus following receipt of IMVAMUNE
time frame: 2 years following initial vaccination
measure: 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
measure: 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
measure: Adverse event and serious adverse event information
time frame: 2 years following initial vaccination
arm group label: Intervention (Liquid Formulation)
arm group type: Experimental
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 group label: Intervention (Lyophilized Formulation)
arm group type: Experimental
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: IMVAMUNE (Liquid Formulation)
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.
arm group label: Intervention (Liquid Formulation)
other name: Modified Vaccinia Ankara (MVA)
other name: MVA-BN
other name: JYNNEOS
other name: IMVANEX
intervention type: Biological
intervention name: IMVAMUNE (Lyophilized Formulation)
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.
arm group label: Intervention (Lyophilized Formulation)
other name: Modified Vaccinia Ankara (MVA)
other name: MVA-BN
other name: JYNNEOS
other name: IMVANEX
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Brett Petersen, MD, MPH
role: Principal Investigator
affiliation: Centers for Disease Control and Prevention
last name: Kinkodi Didine Kaba, MD, PhD
role: Principal Investigator
affiliation: DRC
facility: 
country: Congo, The Democratic Republic of the
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.
PMID: 30445121
responsible party type: Sponsor
mesh term: Smallpox
mesh term: Monkeypox
mesh term: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
sharing ipd: No