A Phase III Randomised, Open Label Trial of an Intradermal or Subcutaneous booster dose of MVA-BN Vaccine to Investigate MPXV Immunogenicity and Safety for Protection Against Mpox in an Intradermally or Subcutaneously Primary Vaccinated Population – an adaptive protocol and a Non-Randomised Trial of a Subcutaneous Booster Dose for Subcutaneously Primary Vaccinated

Overview

Sponsor-declared trial summary

Key facts

Sponsor

The Public Health Agency Of Sweden

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

5 Dec 2025 → ongoing

Decision date (initial)

2026-03-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety

To determine if an MVA-BN booster dose administered ID is non-inferior to SC in inducing a detectable humoral immune-response at 1 month

Secondary objectives 8

1. To determine if an MVA-BN booster dose administered ID is non-inferior to SC in inducing a detectable humoral immune-response at 6 months
2. To compare MPXV-specific immune response between booster dose administered ID vs the control arm, and booster dose administered SC vs the control arm at M1 and M6 post-booster (booster-arms) or post-inclusion (controls)
3. To study durability of humoral immunogenicity (duration of detectable antibodies, peak titres and subsequent decay) of humoral neutralizing capacity and binding MPXV-specific antibodies following a booster dose, taking into consideration route of administration (ID vs SC) and time since primary vaccination.
4. In an immunophenotyping sub-study, to describe and compare the magnitude, stability and phenotypic characteristics of MPXV- and MVA-BN specific memory plasma and B cell responses and cellular responses (T-cell proportion, interferon and interleukin production) by study arm.
5. To study and compare mucosal (oral and rectal) IgA and IgG antibodies by study arm at D0, M1, M3, M6, M12, M24.
6. To describe non-serious and serious adverse reactions of a booster dose, by route of administration, dose interval, sex, and HIV status.
7. To describe and compare breakthrough infections, by study arm, number of doses, route of administration, dose interval, sex, and HIV-status up to M24
8. To determine if a booster dose of an alternative mpox vaccine is non-inferior to MVA-BN SC and/or the MVA-BN ID in inducing a detectable humoral immune-response at 1 month (M1)

Conditions and MedDRA coding

Prevention of monkeypox (mpox) infection

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Adults aged ≥ 18 years old
2. Received a dose of MVA-BN vaccine at least 4 months ago
3. Individuals who are willing and able to participate and have signed written consent to participate in the study.
4. Individuals who expect to be available for monitoring during the entire study period.
5. Men who have sex with men (Swedish, Irish and Belgian trial sites)
6. ≥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)
7. ≥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)
8. Eligible for a booster dose, as recommended by the Haute Autorité de Santé (French trial sites)
9. For women testing negative in pregnancy test (French trial sites)
10. ≥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)

Exclusion criteria 9

1. Individuals with hypersensitivity to the active substance or excipient contained in the vaccine
2. 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
3. Individuals with high-risk exposure with a suspected or confirmed mpox in the 3 weeks prior to signing the informed consent form
4. Positive pregnancy test or persons of childbearing potential
5. Having received more than 2 doses of MVA-BN against mpox
6. Individuals scheduled to receive another vaccine within 14 days prior to or after the MVA-BN booster dose
7. Individuals who are unable to understand the research subject information
8. Individuals participating in another interventional clinical trial
9. Individuals who for other reasons are judged by investigators to be unsuitable for inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. 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.
2. 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: • Geometric mean titers (GMTs) of MPXV- and Vaccinia-specific microneutralizing (NAbs) and MPXV- and vaccinia virus-binding antibodies (BAbs) • Change in sero-response rates (%, SRRs) in detectable antibodies (Nabs or Babs)
3. 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: • GMTs of MPXV- and vaccinia virus binding antibodies and MPXV- & Vaccinia virus-specific microneutralisation antibodies • SRRs (% detectable antibodies from Day 0 forward up to M24.
4. In a subgroup of participants assess and compare • the 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. • Proportion 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) • Levels of detectable interferon and/or IL-2 production in T-cells (CD4 and CD8), assessed by ELISpot (Triplicates)
5. 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: • GMTs of mucosal MPXV- and vaccinia virus-specific binding antibodies • MPXV- and vaccinia virus-specific binding mucosal SRRs (>2-fold increase from Day 0 • Proportion of responders (% with detectable antibodies (NAbs and/or BAbs) by route of administration
6. Incidence and relationship of non-serious and serious adverse reactions (SARs) throughout (M24).
7. Cumulative incidence and clinical presentation of breakthrough infections defined as notified (serologically or PCR-confirmed) MPXV infections by study arm
8. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

The Public Health Agency Of Sweden

Sponsor organisation

The Public Health Agency Of Sweden

Address

Nobels Vag 18

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

The Public Health Agency Of Sweden

Contact name

Enheten för beredskap och smittskyddsdiagnostik

Public contact point

Organisation

The Public Health Agency Of Sweden

Contact name

Enheten för beredskap och smittskyddsdiagnostik

Sponsor responsibilities

Article 77 compliance

The Public Health Agency Of Sweden

Contact point sponsor

The Public Health Agency Of Sweden

Article 77 implementation

The Public Health Agency Of Sweden

Locations

4 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications