The effect of a booster vaccination on protection against the mpox virus: is a booster vaccination with a lower dose as effective as the standard dose (SUBO trial)?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Leiden

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

2 Jan 2025 → ongoing

Decision date (initial)

2024-12-11

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMw grant, program: Infectieziektebestrijding

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To determine non-inferiority of the antibody response two weeks after subcutaneous delivery of the fractional booster dose of MVA-BN vaccine in adults, compared to subcutaneous delivery of the full booster dose.

Secondary objectives 3

1. To describe the kinetics of the VACV, MVA-BN and MPXV-specific binding and MPXV neutralizing antibodies at day 0, 14 and month 6 after booster vaccination.
2. To describe the T-cell responses against VACV and MPXV elicited by subcutaneous de-livery of one-fifth fractional and full doses of MVA-BN vaccine at day 1, 14 and month 6 af-ter booster vaccination.
3. To evaluate safety and tolerability of a third vaccination with a one-fifth dose of MVA-BN administered subcutaneously , and to com-pare the safety profiles of fractional and full doses of MVA-BN vaccine

Conditions and MedDRA coding

mpox (earlier: monkey pox)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Aged 18 years and over, at the time of informed consent
2. Capable of giving personal signed informed consent, which includes compliance with the require-ments listed in this protocol
3. Born after 1974 and having received two doses of MVA-BN vaccination regimen at least one year after the second dose before being recruited
4. Healthy participants who are determined by medical history and clinical judgment of the investiga-tor to be eligible for inclusion in the study. Healthy participants with pre-existing stable disease, de-fined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrolment, can be included
5. Participants who are willing and able to comply with all scheduled visits, vaccination plan, laborato-ry tests, and other study procedures
6. Participants of childbearing potential (i.e. have a uterus and are neither surgically sterilized nor post-menopausal) must not be pregnant or breast-feeding. They should agree to a pregnancy test and use adequate contraception at least up to four weeks following the third vaccination of MVA-BN.

Exclusion criteria 11

1. History of previous smallpox vaccination or evidence of a vaccinia scar
2. Previous clinical or microbiological diagnosis of mpox
3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention (chicken protein, benzonase, gentamicin and ciprofloxacin)
4. Persons living with HIV and CD4-count <350 and/or detectable viral load at their most recent follow up at the outpatient clinic
5. Immunosuppressed individuals with known or suspected immunodeficiency, as determined by histo-ry
6. Individuals with a history of autoimmune disease or an active autoimmune disease, except for type 1 diabetes mellitus and auto-immune diseases of the skin or thyroid that do not require systemic immunosuppression
7. Receipt of systemic corticosteroids withing one month before the study intervention
8. Any physical or psychiatric illness or conditions that could threaten or compromise the health of the participant during the study, influence their ability to participate in the trial or interfere with the interpretation of the study results, as determined by the trial physician
9. Pregnancy or breastfeeding (participants of childbearing potential)
10. Planned pregnancy within four weeks after the injection (participants of childbearing potential)
11. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation (i.e. 7 months)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Geometric mean concentrations (GMC) of VACV-specific antibodies (D0, D14)

Secondary endpoints 9

1. GMC of antibodies against VACV (M6), MVA-BN and MPXV (D0, D14 and M6)
2. Seroconversion for neutralizing antibodies in a subgroup of participants to VACV, MVA-BN, and MPXV (D0, D14, M6)
3. GMT for neutralizing antibodies in a subgroup of participants to VACV, MVA-BN, and MPXV (D0, D14, M6)
4. Percentages of MPXV- and VACV-specific T cells in a subgroup of participants
5. Number of spot forming unit per million cells (IFN-g ELISpot) upon stimulation with peptide gen-erated using VACV sequences
6. Percentages of activated T cells following peptide stimulation
7. Self-reported local and systemic reactions over a 7-day period, or until symptom remission, using an (electronical) diary and control visits at day 14 and month 6 months after booster vaccination
8. Adverse events (AEs) until one week after vaccination or until symptom remission, using an (electronical) diary and control visits at day 14 and month 6 months after booster vaccination
9. Serious AEs (SAEs) until six months after vaccination

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Leo Visser

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Leo Visser

Locations

1 EU/EEA country · 3 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 13 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