Clinical trial NCT03745131: Cohort Study of Healthcare Workers Receiving Imvanex®
Official title: A Cohort Study of Serological Responses to MVA-BN Smallpox Vaccine (Imvamex®) Administered During a Monkeypox Outbreak in the UK
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Monkeypox
Keywords: Immunisation
Modified Vaccinia Ankara
Imvanex
Imvamune
Vaccine
Lead sponsor: Public Health England
Sponsor class: OTHER_GOV
Collaborators: name: Bavarian Nordic
First posted: 2018-11-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthcare workers at NHS Airborne HCID Centres, and healthcare workers at other NHS hospitals that cared for monkeypox cases before they were transferred to HCID Centres.

Brief summary: During an outbreak of monkeypox in the UK in 2018, a third generation smallpox vaccine, Imvanex, was used for the first time to immunise healthcare workers who had been, or were expected to be, in contact with cases of monkeypox. This study will examine the antibody responses in these healthcare workers compared to control groups, to provide evidence that the vaccine can produce a response consistent with protection when used in this context.

Detailed description: This study intends to describe antibody responses to a third generation smallpox vaccine, Imvanex® (MVA-BN, Bavarian Nordic GmBH; also known as Imvamune®), in cohorts of individuals who received the vaccine for pre-exposure or post-exposure prophylaxis against monkeypox during a monkeypox outbreak in the UK. In addition to quantifying anti-vaccinia virus antibody responses to vaccine, the study intends to demonstrate that vaccine-induced antibodies neutralise the specific monkeypox viruses involved in the UK outbreak, and also reference monkeypox viruses. The use of Imvanex® during the UK outbreak represents the first ever use of Imvanex® as a public health intervention for a monkeypox outbreak, and this study will provide an opportunity to quantify and characterise antibody responses to Imvanex® administered in a non-trial setting.

Eligibility criteria: Inclusion criteria for pre-exposure prophylaxis cases:

* A High Consequence Infectious Disease (HCID) Centre healthcare worker involved in the care of a confirmed monkeypox case
* AND the individual has received Imvanex® during the outbreak period
* AND no known unprotected exposure to a monkeypox case (i.e. pre-exposure indication for vaccination)

Inclusion criteria for post-exposure prophylaxis cases:

* A healthcare worker
* AND the individual has received Imvanex® during the outbreak period
* AND unprotected exposure to a monkeypox case is believed to have occurred (i.e. post-exposure indication for vaccination)

Inclusion criteria for control group 1 (unvaccinated HCID staff caring for confirmed cases):

* A High Consequence Infectious Disease (HCID) Unit healthcare worker involved in the care of a confirmed monkeypox case
* AND the individual has NOT received Imvanex® during the outbreak period
* AND no known unprotected exposure to a monkeypox case

Inclusion criteria for control group 2 (general healthcare workers):

* A healthcare worker NOT involved in the care of a confirmed monkeypox case
* AND the individual has NOT received Imvanex® during the outbreak period
* AND no known unprotected exposure to a monkeypox case

Exclusion criteria for all participants:

* Refusal by participant
* Age less than 18 years

Primary outcomes:
measure: Antibody responses to first dose of Imvanex®
timeFrame: 28-56 days following immunisation
measure: Antibody titres following first dose of Imvanex®
timeFrame: 28-56 days following immunisation
Secondary outcomes:
measure: Antibody responses to second dose of Imvanex®
timeFrame: 28-56 days following immunisation
measure: Antibody titres following second dose of Imvanex®
timeFrame: 28-56 days following immunisation
measure: Neutralising antibody responses to first dose of Imvanex®
timeFrame: 28-56 days following immunisation
measure: Adverse events reported following vaccination with Imvanex®
timeFrame: 28-56 days following immunisation
Other outcomes:
Locations:
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust
state: Lancashire
city: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen University Hospitals NHS Trust
state: Merseyside
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle Hospitals NHS Foundation Trust
state: Tyne And Wear
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Public Health England
name: William Jake Dunning, MRCP PhD
role: STUDY_DIRECTOR
affiliation: Public Health England
name: Meera Chand, FRCPath
role: STUDY_DIRECTOR
affiliation: Public Health England
name: Sema Mandal, MRCP FFPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Public Health England
name: Nicholas Andrews, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Public Health England
name: Timothy Brooks, FRCPath
role: PRINCIPAL_INVESTIGATOR
affiliation: Liverpool University Hospitals NHS Foundation Trust
name: Michael Beadsworth, MD MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Free London NHS Foundation Trust
name: Michael Jacobs, FRCP PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Newcastle Hospitals NHS Foundation Trust
name: Matthias Schmid, MD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Christopher Meadows, FRCP FRCA
role: PRINCIPAL_INVESTIGATOR
affiliation: Blackpool Teaching Hospitals NHS Foundation Trust
name: Peter Flegg, MD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Bavarian Nordic
name: Heinz Weidenthaler
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vaughan A, Aarons E, Astbury J, Balasegaram S, Beadsworth M, Beck CR, Chand M, O'Connor C, Dunning J, Ghebrehewet S, Harper N, Howlett-Shipley R, Ihekweazu C, Jacobs M, Kaindama L, Katwa P, Khoo S, Lamb L, Mawdsley S, Morgan D, Palmer R, Phin N, Russell K, Said B, Simpson A, Vivancos R, Wade M, Walsh A, Wilburn J. Two cases of monkeypox imported to the United Kingdom, September 2018. Euro Surveill. 2018 Sep;23(38):1800509. doi: 10.2807/1560-7917.ES.2018.23.38.1800509.
citation: Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Ahmad S, Hasan H, Ahmad Suhaimi NA, Albakri KA, Abedalbaset Alzyoud A, Kadir R, Mohamud R. Comprehensive literature review of monkeypox. Emerg Microbes Infect. 2022 Dec;11(1):2600-2631. doi: 10.1080/22221751.2022.2132882.