Break-through Infection Following Mpox vaccinatIon (REMAIN)

Break-through Infection Following Mpox vaccinatIon: Target Trial Emulation

The purpose of this study is to assess the protection of smallpox preexposure vaccination against infection with mpox in real-world individuals with risk factors for mpox.

Study Overview

• Status: Active, not recruiting
• Conditions: Mpox
• Intervention / Treatment: Drug: Mpox Vaccine

Detailed Description

A Target Trial Emulation study that tries to emulate the sequential specification of a target trial will be conducted measuring and controlling confounders when there is a common cause of vaccination and outcome event.

Participants will be provided with a Quick response (QR) code to access the RedCap study platform, which will guide them to the enrolment process. If the participant accepts and meets all the inclusion and none of the exclusion criteria, they will be directed to a baseline survey to self-collect sociodemographic data and information regarding risk factors, sexual behaviour, vaccination, and exposure to mpox.

Newly vaccinated participants will be matched 1:1 to unvaccinated controls. The matching will be performed based on the site of recruitment, and self-reported baseline sexual health and practices. Vaccinated and unvaccinated participants will be matched on variables associated with the probability of infection.

Follow-up will include regular surveys every month from the index date (i.e., enrolment date in the unvaccinated group, or vaccination date for the vaccinated group), to collect data on change on risk factors, sexual behaviour in the past month, vaccination status, and exposure to mpox. The participant will be asked to self-report if they develop symptoms suggestive of mpox, and the study platform will direct them to a specific mpox infection survey.

For each participant, follow-up will end at the earliest of the following events: mpox infection, voluntary withdraw, or the end of the study period. A health record review will be conducted to corroborate the diagnosis of new cases and to provide validity to the self-report.

• Study Type: Observational
• Enrollment (Estimated): 4638

Contacts and Locations

• Study Contact: Name: Oriol Mitjà, PhD; Phone Number: +34934978944; Email: oriolmitja@hotmail.com
• Study Contact Backup: Name: Clara Suñer, PhD; Email: csuner@lluita.org

Study Locations

• Chile
  • Región Metropolitana
    • Santiago de Chile, Región Metropolitana, Chile, 8360154
      • Hospital Clinico San Borja Arriarán
• Panama
  • Panamá, Panama
    • Instituto Conmemorativo Gorgas de Estudios de la Salud (ICGES)
• Peru
  • Arequipa, Peru
    • Hospital Regional III Honorio Delgado
  • Lima, Peru, 15082
    • Hospital Nacional Arzobispo Loayza
  • Trujillo, Peru, 13011
    • Hospital Regional Docente de Trujillo
• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias I Pujol Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Vaccinated and unvaccinated individuals who have risk factors for mpox infection and do not have a past history of mpox infection.

Description

Inclusion Criteria:

1. Individuals aged 18 years or older.

2. Individuals with general risk factors for mpox infection, as currently defined by the local guidelines for vaccination. These risk factors include at least one of the following items:

   • Individual-reported use of HIV pre-exposure prophylaxis (PrEP).
   • Individual-reported chemsex practices
   • Individual-reported multiple sexual partners.
   • Individuals with a history of a sexually transmitted infection (STI) in the past year.
   • Individuals living with HIV infection.
3. Signature of informed consent.

Exclusion Criteria:

1. Unable to provide signature of informed consent.
2. Past infection with monkeypox.
3. Past smallpox vaccination.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Unvaccinated; Unvaccinated individuals who have risk factors for mpox infection and do not have a past history of mpox infection
Vaccinated; Vaccinated individuals with smallpox and mpox vaccine (Live Modified Vaccinia Virus Ankara) who have risk factors for monkeypox infection and do not have a past history of mpox infection.	Drug: Mpox Vaccine; Vaccination with smallpox and mpox vaccine (Live Modified Vaccinia Virus Ankara)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymerase chain reaction (PCR)-confirmed mpox infection	Mpox PCR positivity in participants with mpox infection symptoms	From 14 days after the index date to twelve months after the index date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Description of systemic and skin reactions	One month after vaccination
Polymerase chain reaction (PCR)-confirmed mpox infection	Mpox PCR positivity in participants with mpox infection symptoms	From immediately after the index date to twelve months after the index date
Duration of general symptoms	Time from onset to resolution of general symptoms in participants with PCR-confirmed mpox infection (in days).	From 14 days after the index date to twelve months after the index date
Severity of rash	Number of mpox lesions (lesions count)	From 14 days after the index date to twelve months after the index date
Duration of skin rash	Time from onset to resolution of skin rash in participants with PCR-confirmed	From 14 days after the index date to twelve months after the index date
Medical treatment	Requirement of medical treatment (yes/no)	From 14 days after the index date to twelve months after the index date
Hospitalization	Requirement of hospital admission (yes/no)	From 14 days after the index date to twelve months after the index date
Scarring	Residual scarring after mpox (yes/no)	From 14 days after the index date to twelve months after the index date

Collaborators and Investigators

• Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Collaborators: London School of Hygiene and Tropical Medicine; Hospital Clinic of Barcelona; Germans Trias i Pujol Hospital; Harvard School of Public Health (HSPH); Hospital Universitario 12 de Octubre; Madrid Salud; Hospital Vall d'Hebron; Public Health Service of Madrid; Department of Health, Generalitat de Catalunya; BCN Checkpoint; Hospital Nacional Arzobispo Loayza; Centro de Saluld Sandoval; Centro de Salud Montesa; Hospital Regional III Honorio Delgado; Hospital Regional Docente de Trujillo; Ministerio de Salud de Panamá; Fundación Arriaran; Instituto Conmemorativo Gorgas de Estudios de la Salud

Publications and helpful links

General Publications

• Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, Hernan MA, Lipsitch M, Kohane I, Netzer D, Reis BY, Balicer RD. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med. 2021 Sep 16;385(12):1078-1090. doi: 10.1056/NEJMoa2110475. Epub 2021 Aug 25.

Helpful Links

• Recommendations of experts in trial design to World Health Organization
• Spanish incidence estimation document for the calculation of the number of participants

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: August 27, 2022
• First Submitted That Met QC Criteria: August 27, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Monkeypox; Mpox; Mpox Vaccine; Intradermal Mpox vaccine
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Breakthrough Infections
• Other Study ID Numbers: REMAIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon request after publication
• IPD Sharing Time Frame: After Publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No