MODIFIED VACCINIA ANKARA – BAVARIAN NORDIC LIVE VIRUS for Monkeypox (mpox)

Inclusion criteria

• {"criterion_text":"- Adults aged ≥ 18 years old\n- ≥18 years old who 4 months ago or earlier received 1x10^8 TCID50 MVA-BN in a 2-dose SC or 2x10^7 TCID50 MVA-BN ID regime approximately four to twelve weeks apart in line with public health recommendations in Belgium, or previously smallpox vaccinated individuals who have received only one dose 1x10^8 TCID50 MVA-BN SC as a primary regimen. (Belgian trial sites)\n- Received a dose of MVA-BN vaccine at least 4 months ago\n- Individuals who are willing and able to participate and have signed written consent to participate in the study.\n- Individuals who expect to be available for monitoring during the entire study period.\n- Men who have sex with men (Swedish, Irish and Belgian trial sites)\n- ≥18 years old who 4 months ago or earlier received 2x10^7 TCID50 MVA-BN in a 2-dose ID regime approximately four weeks apart in line with public health recommendations in Sweden, or previously smallpox vaccinated individuals who have received only one dose 2x10^7 TCID50 MVA-BN ID as a primary regimen. (Swedish trial sites)\n- ≥18 years old who 4 months ago or earlier received 1x10^8 TCID50 MVA-BN in a 2-dose SC or ID regime approximately four weeks apart in line with public health recommendations in Ireland, or previously smallpox vaccinated individuals who have received only one dose 1x10^8 TCID50 MVA-BN SC as a primary regimen. (Irish trial sites)\n- Eligible for a booster dose, as recommended by the Haute Autorité de Santé (French trial sites)\n- For women testing negative in pregnancy test (French trial sites)"}

Exclusion criteria

• {"criterion_text":"- Individuals with hypersensitivity to the active substance or excipient contained in the vaccine\n- Individuals with a history of mpox (including laboratory-confirmed), or any orthopoxvirus (except small pox vaccination) prior to the vaccination offered for protection against mpox, based on volunteer-reported medical history\n- Individuals with high-risk exposure with a suspected or confirmed mpox in the 3 weeks prior to signing the informed consent form\n- Positive pregnancy test or persons of childbearing potential\n- Having received more than 2 doses of MVA-BN against mpox\n- Individuals scheduled to receive another vaccine within 14 days prior to or after the MVA-BN booster dose\n- Individuals who are unable to understand the research subject information\n- Individuals participating in another interventional clinical trial\n- Individuals who for other reasons are judged by investigators to be unsuitable for inclusion"}

Primary endpoints

• {"endpoint_text":"- Non-inferiority (max 10% difference) between ID and SC booster arms, in detectable MPXV- and vaccinia virus-binding antibodies (BAbs) at 1 month (M1) post-booster assuming that at least 80% (and not <70%) of participants in both booster arms will have detectable BAbs.","definition_or_measurement_approach":"Detectable MPXV- and vaccinia virus-binding antibodies (BAbs) at 1 month (M1) post-booster; non-inferiority margin: max 10% difference; assumption that ≥80% (and not <70%) of participants in both booster arms will have detectable BAbs."}

Secondary endpoints

• {"endpoint_text":"- Non-inferiority (max 10% difference) between ID and SC booster arms, in detectable MPXV- and vaccinia virus binding antibodies (BAbs) at 6 months post-booster assuming that 80% (and not <70%) of participants in both booster arms will have detectable BAbs.\n- Compare MPXV and Vaccinia virus-specific humoral response between ID booster arm vs control, and SC booster arm vs control at M1 and M6 post-inclusion, using: •\tGeometric mean titers (GMTs) of MPXV- and Vaccinia-specific microneutralizing (NAbs) and MPXV- and vaccinia virus-binding antibodies (BAbs) •\tChange in sero-response rates (%, SRRs) in detectable antibodies (Nabs or Babs)\n- Compare the humoral response (GMT, rate of decay from peak and % with detectable neutralizing and binding antibodies (NAbs and BAbs) by route of administration (Booster-ID vs Booster-SC) over time assessed at D0, D7 (for the participants in the sub-study), M1, M3, M6, M12 and M24 using: •\tGMTs of MPXV- and vaccinia virus binding antibodies and MPXV- & Vaccinia virus-specific microneutralisation antibodies •\tSRRs (% detectable antibodies from Day 0 forward up to M24.\n- In a subgroup of participants assess and compare •\tthe number, diversity, and functionality of MPXV- and MVA-BN specific memory plasma cells and B cells by study arm, at D0, D7, M1, M3, M6, M24. •\tProportion of T-cells (CD4 and CD8) with detectable interferon and/or IL-2 production after stimulation by Mpox and/or MVA-BN antigens, assessed by ELISpot (triplicates) •\tLevels of detectable interferon and/or IL-2 production in T-cells (CD4 and CD8), assessed by ELISpot (Triplicates)\n- In a subgroup of participants: assess and compare oral and rectal mucosa IgA and IgG antibody response (ELISA MSD) at D0, D7, M1, M3, M6, M24 using: •\tGMTs of mucosal MPXV- and vaccinia virus-specific binding antibodies •\tMPXV- and vaccinia virus-specific binding mucosal SRRs (>2-fold increase from Day 0 •\tProportion of responders (% with detectable antibodies (NAbs and/or BAbs) by route of administration\n- Incidence and relationship of non-serious and serious adverse reactions (SARs) throughout (M24).\n- Cumulative incidence and clinical presentation of breakthrough infections defined as notified (serologically or PCR-confirmed) MPXV infections by study arm\n- Non-inferiority (max 10% difference) between an alternative vaccine and ID and SC MVA-BN booster arms (given that these are non-inferior to each other ie less than 10% difference), in detectable MPXV- and VACV- BAbs at M1 post-booster assuming that at least 80% (and not <70%) of participants in both booster arms will have detectable BAbs.","definition_or_measurement_approach":"Endpoints measured using detectable MPXV- and Vaccinia-specific binding antibodies (BAbs) and microneutralising antibodies (NAbs); GMTs, SRRs (% detectable), rate of decay from peak; ELISpot for T-cell responses; ELISA MSD for mucosal IgA/IgG; adverse reaction incidence tracked to M24; breakthrough infections confirmed serologically or by PCR; non-inferiority margins as specified (max 10% difference). Timepoints: D0, D7 (sub-study), M1, M3, M6, M12, M24."}

Ireland

Earliest CTIS Part Ii Submission Date

27-01-2025

Latest Decision Or Authorization Date

09-09-2025

Processing Time Days

225

Number Of Sites

5

Number Of Participants

100

France

Earliest CTIS Part Ii Submission Date

31-01-2025

Latest Decision Or Authorization Date

05-09-2025

Processing Time Days

217

Number Of Sites

10

Number Of Participants

150

Sweden

Earliest CTIS Part Ii Submission Date

06-01-2025

Latest Decision Or Authorization Date

05-09-2025

Processing Time Days

242

Number Of Sites

1

Number Of Participants

295

Belgium

Earliest CTIS Part Ii Submission Date

29-01-2026

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

71

Number Of Sites

1

Number Of Participants

95

Primary sponsor

Full Name

The Public Health Agency Of Sweden

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Sweden