Cohort Study of Healthcare Workers Receiving Imvanex®

Sponsor

Public Health England (Other)

Overall Status

Completed

CT.gov ID

NCT03745131

Collaborator

Bavarian Nordic (Industry)

120

Enrollment

Locations

Actual Duration (Months)

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Monkeypox	Other: Blood draw

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.

Study Design

Study Type:

Observational

Actual Enrollment :

120 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Cohort Study of Serological Responses to MVA-BN Smallpox Vaccine (Imvamex®) Administered During a Monkeypox Outbreak in the UK

Actual Study Start Date :

Oct 30, 2018

Actual Primary Completion Date :

May 30, 2019

Actual Study Completion Date :

Nov 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Pre-exposure prophylaxis recipients 40 healthcare workers who provide specialist medical care to patients with monkeypox and who received vaccine as pre-exposure prophylaxis.	Other: Blood draw Blood draw to obtain serum to determine anti-orthopox antibody titres.
Post-exposure prophylaxis recipients 40 healthcare workers who received vaccine as post-exposure prophylaxis following monkeypox-exposure risk assessments.	Other: Blood draw Blood draw to obtain serum to determine anti-orthopox antibody titres.
Control Group 1 20 healthcare workers who provided specialist medical care to patients with monkeypox but declined the offer of vaccine as pre-exposure prophylaxis.	Other: Blood draw Blood draw to obtain serum to determine anti-orthopox antibody titres.
Control Group 2 Healthcare workers not involved in the care of, and have not had known exposure to, patients with monkeypox and, therefore, were not offered vaccine.	Other: Blood draw Blood draw to obtain serum to determine anti-orthopox antibody titres.

Outcome Measures

Primary Outcome Measures

Antibody responses to first dose of Imvanex® [28-56 days following immunisation]
The proportion of participants with anti-orthopox antibodies when measured at a single time point between days 28 and 56 following first dose of Imvanex®.
Antibody titres following first dose of Imvanex® [28-56 days following immunisation]
Geometric mean titres (GMTs) of anti-orthopox antibodies when measured at a single time point between days 28 and 56 following first dose of Imvanex®.

Secondary Outcome Measures

Antibody responses to second dose of Imvanex® [28-56 days following immunisation]
The proportion of participants who have anti-orthopox antibodies when measured at day 14 following the second dose of Imvanex®, if a subset of individuals receive a second dose of Imvanex® during the lifetime of the study.
Antibody titres following second dose of Imvanex® [28-56 days following immunisation]
The geometric mean titres (GMTs) of anti-orthopox antibodies when measured at day 14 following the second dose of Imvanex®, if a subset of individuals receive a second dose of Imvanex®.
Neutralising antibody responses to first dose of Imvanex® [28-56 days following immunisation]
The proportion of participants who have demonstrable neutralising antibodies against the specific monkeypox viruses involved in the UK outbreak, in addition to reference monkeypox viruses.
Adverse events reported following vaccination with Imvanex® [28-56 days following immunisation]
Adverse events and serious adverse events by reported frequencies (reported retrospectively).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blackpool Teaching Hospitals NHS Foundation Trust	Blackpool	Lancashire	United Kingdom	FY3 8NR
2	Royal Liverpool and Broadgreen University Hospitals NHS Trust	Liverpool	Merseyside	United Kingdom	L7 8XP
3	Newcastle Hospitals NHS Foundation Trust	Newcastle Upon Tyne	Tyne And Wear	United Kingdom	NE1 4LP
4	Royal Free London NHS Foundation Trust	London		United Kingdom	NW3 2QG
5	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

Public Health England
Bavarian Nordic

Investigators

Study Director: William Jake Dunning, MRCP PhD, Public Health England
Study Director: Meera Chand, FRCPath, Public Health England
Principal Investigator: Sema Mandal, MRCP FFPH, Public Health England
Principal Investigator: Nicholas Andrews, PhD, Public Health England
Principal Investigator: Timothy Brooks, FRCPath, Public Health England
Principal Investigator: Michael Beadsworth, MD MRCP, Liverpool University Hospitals NHS Foundation Trust
Principal Investigator: Michael Jacobs, FRCP PhD, Royal Free London NHS Foundation Trust
Principal Investigator: Matthias Schmid, MD FRCP, Newcastle Hospitals NHS Foundation Trust
Principal Investigator: Christopher Meadows, FRCP FRCA, Guy's and St Thomas' NHS Foundation Trust
Principal Investigator: Peter Flegg, MD FRCP, Blackpool Teaching Hospitals NHS Foundation Trust
Principal Investigator: Heinz Weidenthaler, Bavarian Nordic GmbH