MonkeypoxPhase 4SMARTNCT05745987
Smallpox Vaccine for Mpox Post-Exposure Prophylaxis: A Cluster RCT
A Phase 4 study testing Bavarian Nordic smallpox vaccine and Typhoid VI Polysaccharide Vaccine Injectable Solution in people with Monkeypox, run by McMaster University at 10 sites in 3 countries.
Trial summary
A cluster randomized controlled trial to determine if smallpox vaccine reduces secondary cases and symptom severity in persons exposed to mpox. Read more about this study
- Who is it for?
- Ages 2 years and olderHealthy volunteers can take part
- Conditions the study is for
- Monkeypox
- What is being tested?
- Bavarian Nordic smallpox vaccine and Typhoid VI Polysaccharide Vaccine Injectable Solution
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,000 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 17 Sep 2024to 20 Oct 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Household member of person with laboratory confirmed mpox
- Age ≥ 2 years
- Within 14 days of onset of illness in mpox index case
Who cannot join
- Pregnancy
- Breastfeeding
- Past serious allergic reaction to study vaccine components
- Previous smallpox vaccination
- Current or planned use of another investigational drug at any point during study participation
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Nigeria8 sites
Federal Medical Center
Abuja
University of Abuja Teaching Hospital
Abuja
University of Ibadan
Ibadan
Irrua Specialist Teaching Hospital
Irrua
Aminu Kano Teaching Hospital
Kano
Lagos University Teaching Hospital
Lagos
Niger Delta Teaching Hospital
Okolobiri
University of Port Harcourt Teaching Hospital
Port Harcourt
Democratic Republic of the Congo1 site
Catholic University of Bukavu
Kinshasa, Bukavu
About this study
Official title: SMART (Smallpox Vaccine for Mpox Post-Exposure Prophylaxis: A Cluster Randomized Controlled Trial)
A cluster randomized controlled trial to determine if smallpox vaccine reduces secondary cases and symptom severity in persons exposed to mpox.
Read the detailed description
A pragmatic, adaptive, multi-site, cluster randomized trial where households with one or more persons confirmed to have mpox will be randomized to smallpox vaccine or control. The co-primary outcomes are RT-PCR confirmed mpox and symptom severity.
- Conditions
- Monkeypox
- Being tested
- Bavarian Nordic smallpox vaccine, Typhoid VI Polysaccharide Vaccine Injectable Solution
- Keywords
- mpox
- Medical subject headings
- Mpox, Monkeypox
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bavarian Nordic smallpox vaccineDrug
Also called Imvamune
A single dose of the Bavarian Nordic smallpox vaccine will be given at baseline.
Typhoid VI Polysaccharide Vaccine Injectable SolutionDrug
A single dose of the typhoid vaccine will be given at baseline.
| Study group | Role | What they receive |
|---|---|---|
| Smallpox vaccine | Experimental | Participants will receive the Bavarian Nordic smallpox vaccine 0.5 ml single-dose Receives: Drug: Bavarian Nordic smallpox vaccine |
| Typhoid vaccine | Active comparator | Participants will receive the Typhim Vi® typhoid vaccine 0.5 ml single-dose Receives: Drug: Typhoid VI Polysaccharide Vaccine Injectable Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
PCR-confirmed Mpox
To evaluate if smallpox vaccine vs control prevents RT-PCR confirmed mpox
Measured: 8 weeks
Symptom severity
To evaluate if smallpox vaccine vs control affects symptom severity
Measured: 8 weeks
Secondary outcomes (7)
Resolution of skin lesions
To assess the time to resolution (i.e. a new skin layer has formed) of any skin lesion
Measured: 8 weeks
Number of skin lesions
To assess the number of skin lesions for any participants who develop mpox
Measured: 8 weeks
Self-reported Quality of Life
To assess the QOL of participants using the World Health Organization Quality of Life Scale
Measured: 8 weeks
Mpox complications
To assess longitudinal complications for any participants who develop mpox
Measured: 8 weeks
Mpox Pain
To assess pain using an adapted Zoster Brief Pain Inventory
Measured: 8 weeks
Hospitalization
To determine all cause hospitalization over the study period
Measured: 8 weeks
Mortality
To determine all cause mortality over the study period
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2023
- Study start17 Sep 2024
- Primary completion22 Apr 2026
- Study completion20 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MonkeypoxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each group will be randomly selected to receive the smallpox vaccine or the typhoid vaccine
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Loeb, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05745987
- Sponsor's protocol ID
- SMART RCT
- Acronym
- SMART
- Status last verified
- Aug 2026
- First submitted
- 10 Feb 2023
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SMART (Smallpox Vaccine for Mpox Post-Exposure Prophylaxis: A Cluster Randomized Controlled Trial)
- ClinicalTrials.gov ID
- NCT05745987
- Acronym / sponsor ID
- SMART / SMART RCT
- Conditions
- Monkeypox
- Keywords
- mpox
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 17 Sep 2024 (actual)
- Primary completion
- 22 Apr 2026 (actual)
- Study completion
- 20 Oct 2026 (estimated)
- First posted
- 27 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A cluster randomized controlled trial to determine if smallpox vaccine reduces secondary cases and symptom severity in persons exposed to mpox.
Detailed description
A pragmatic, adaptive, multi-site, cluster randomized trial where households with one or more persons confirmed to have mpox will be randomized to smallpox vaccine or control. The co-primary outcomes are RT-PCR confirmed mpox and symptom severity.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Each group will be randomly selected to receive the smallpox vaccine or the typhoid vaccine
| Arm | Type | Receives |
|---|---|---|
| Smallpox vaccine | Experimental | Drug: Bavarian Nordic smallpox vaccineParticipants will receive the Bavarian Nordic smallpox vaccine 0.5 ml single-dose |
| Typhoid vaccine | Active comparator | Drug: Typhoid VI Polysaccharide Vaccine Injectable SolutionParticipants will receive the Typhim Vi® typhoid vaccine 0.5 ml single-dose |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Household member of person with laboratory confirmed mpox
- Age ≥ 2 years
- Within 14 days of onset of illness in mpox index case
Key exclusion criteria (5 listed)
- Pregnancy
- Breastfeeding
- Past serious allergic reaction to study vaccine components
- Previous smallpox vaccination
- Current or planned use of another investigational drug at any point during study participation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bavarian Nordic smallpox vaccineAlso: ImvamuneA single dose of the Bavarian Nordic smallpox vaccine will be given at baseline. | Drug | Smallpox vaccine |
| Typhoid VI Polysaccharide Vaccine Injectable SolutionA single dose of the typhoid vaccine will be given at baseline. | Drug | Typhoid vaccine |
Primary outcome
PCR-confirmed Mpox
Time frame: 8 weeks
To evaluate if smallpox vaccine vs control prevents RT-PCR confirmed mpox
Symptom severity
Time frame: 8 weeks
To evaluate if smallpox vaccine vs control affects symptom severity
7 secondary outcomes
Resolution of skin lesions
Time frame: 8 weeks
Number of skin lesions
Time frame: 8 weeks
Self-reported Quality of Life
Time frame: 8 weeks
Mpox complications
Time frame: 8 weeks
Mpox Pain
Time frame: 8 weeks
Hospitalization
Time frame: 8 weeks
Mortality
Time frame: 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Monkeypox
Active, not recruitingPhase 1
A Clinical Trial Evaluating the Monkeypox Recombinant Protein Vaccine
Health Volunteer
RecruitingObservational study
Evaluation of Effectiveness and Safety of LC16m8 Mpox Vaccine in the Democratic Republic of Congo (DRC)
Mpox (Monkeypox), Mpox
Enrolling by invitationObservational study
New York City Observational Study of Mpox Immunity
Monkeypox, Mpox
Enrolling by invitation
Smart Analysis and Decision-Making for Emerging Infectious Diseases
Emerging Infectious Diseases, COVID-19
RecruitingPhase 2
A Randomized Clinical Trial Investigating the Safety, Reactogenicity, and Immunogenicity After Immunization With an mRNA-based Mpox Vaccine Candidate in Africa
Mpox (Monkeypox), Smallpox
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Loeb, MD principal investigator
McMaster University
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bavarian Nordic smallpox vaccine and Typhoid VI Polysaccharide Vaccine Injectable Solution in people with Monkeypox, run by McMaster University at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Nigeria, Democratic Republic of the Congo, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PCR-confirmed Mpox (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.