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A Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NP+M1 in Healthy Adults

Primary Purpose

Influenza

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
MVA-NP+M1
MVA-NP+M1
MVA-NP+M1
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring Influenza, Vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy adult aged 18 or over, no upper age limit
  • Resident in or near Oxford for the duration of the vaccination study
  • Able and willing (in the Investigators' opinions) to comply with all study requirements
  • Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
  • For females, a negative pregnancy test on the day of vaccination and agreement to practice effective contraception for the duration of the study.
  • Agreement to refrain from blood donation during the course of the study
  • Written informed consent

Exclusion Criteria:

  • Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
  • Prior receipt of a recombinant MVA vaccine
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
  • Any history of anaphylaxis in reaction to vaccination
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  • History of serious psychiatric condition
  • Any chronic illness requiring ongoing or awaiting hospital specialist supervision, other than minor surgical procedures and follow up of surgery over 6 months prior to screening.
  • Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units every week)
  • Seropositive for hepatitis B surface antigen (HBsAg)
  • Seropositive for hepatitis C virus (antibodies to HCV)
  • For females, pregnancy, lactation or willingness/intention to become pregnant during the study
  • Any other significant disease, disorder or finding, which, in the opinion of the Investigators, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study.
  • Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis, as determined by the investigators.

Sites / Locations

  • Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

1. MVA-NP+M1 ID

2. MVA-NP+M1 IM

3. MVA-NP+M1 IM upper age group

Arm Description

12 volunteers to receive MVA-NP+M1 via ID route

16 volunteers to receive MVA-NP+M1 via IM route

30 volunteers to receive MVA-NP+M1 via IM route

Outcomes

Primary Outcome Measures

To assess the safety of a new influenza vaccine, MVA-NP+M1, when administered to healthy volunteers.

Secondary Outcome Measures

To assess the cellular immune response generated by a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.

Full Information

First Posted
July 16, 2009
Last Updated
November 28, 2012
Sponsor
University of Oxford
Collaborators
Wellcome Trust
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1. Study Identification

Unique Protocol Identification Number
NCT00942071
Brief Title
A Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NP+M1 in Healthy Adults
Official Title
A Phase I Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NP+M1 in Healthy Adults
Study Type
Interventional

2. Study Status

Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
Wellcome Trust

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is an open label phase I study, to assess the safety of a novel influenza vaccine, MVA-NP+M1. All volunteers recruited will be healthy. Twelve volunteers will be administered with a single dose of 5 x 10^7 pfu of MVA-NP+M1 via the Intradermal (ID) route (group 1). Sixteen volunteers will receive Intramuscular (IM) MVA-NP+M1. The first 8 volunteers will be administered a single dose of 5 x 10^7 pfu of MVA-NP+M1 followed by a further eight receiving 2.5 x 10^8 pfu of MVA-NP+M1 (group 2). The 3rd group will be split into 3 groups of 10 volunteers in the age ranges 50-59, 60-69 and 70 and above and administered intramuscularly with a single dose of 1.5 x 10^8 pfu of MVA-NP+M1. Safety data will be collected. The secondary aim of this study will be to assess the cellular immune responses generated by each dose.
Detailed Description
Antibodies against the external proteins of influenza can prevent the virus from infecting cells and either prevent infection or limit the spread of infection. However the surface proteins are highly variable and there is little antibody cross-reactivity between variants. Once a cell has been infected with the virus, it is then vulnerable to T cell attack resulting in the destruction of infected cells so that no more virus can be produced and the infection is controlled. There is evidence from clinical trials of influenza challenge, and animal models that T cell responses can protect in the absence of antibodies. Additionally, since T cells can recognise the highly conserved internal proteins of influenza, cross-subtype protection can be achieved. Seasonal influenza infection results in a T cell response to the virus which can protect against subsequent infection. However over the course of a few years these responses decline below protective levels. The new vaccine being tested in this study is designed to boost these T cell responses back to protective levels. Even responses that may be too low to be reliably quantified by currently available assays may still be boosted to high levels by a single dose of recombinant MVA. Since the internal proteins vary little between influenza subtypes, this could result in a 'universal' vaccine against influenza A. If the need to continually reformulate the vaccine in response to mutations in the viral coat proteins can be removed, the universal vaccine could be produced in large amounts and used more widely than the existing seasonal 'flu vaccines, thus protecting the population against currently circulating viruses and new virus types that are at present only found in avian species. There is very little polymorphism of NP and M1 between influenza A isolates. NP is 92% identical between H3N2 and H1N1 strains, and 91% identical between H3N2 and H5N1 strains. M1 is 95% identical between H3N2 and H1N1 strains, and 93% identical between H3N2 and H5N1 strains. This low level of variation appears to allow strong T cell cross-reactivity. MVA is a highly attenuated strain of vaccinia virus that is unable to replicate efficiently in human cell lines and most mammalian cells. Viral replication is blocked at a late stage of virion assembly, so, importantly, viral and recombinant protein synthesis is unimpaired. This means that MVA is an efficient single round expression vector, incapable of causing infection in mammals. Replication-deficient recombinant MVA has been seen as an exceptionally safe viral vector. This safety in man is consistent with the avirulence of MVA in animal models, where recombinant MVAs have also been shown to be protectively immunogenic as vaccines against viral diseases and cancer. Importantly for a vaccine which may eventually be used in a large proportion of the population, recombinant MVAs expressing HIV antigens have been shown to be safe and immunogenic in HIV-infected subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
Influenza, Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1. MVA-NP+M1 ID
Arm Type
Experimental
Arm Description
12 volunteers to receive MVA-NP+M1 via ID route
Arm Title
2. MVA-NP+M1 IM
Arm Type
Experimental
Arm Description
16 volunteers to receive MVA-NP+M1 via IM route
Arm Title
3. MVA-NP+M1 IM upper age group
Arm Type
Experimental
Arm Description
30 volunteers to receive MVA-NP+M1 via IM route
Intervention Type
Biological
Intervention Name(s)
MVA-NP+M1
Intervention Description
1. Intradermal injection at 5 x 10^7 pfu at day 0
Intervention Type
Biological
Intervention Name(s)
MVA-NP+M1
Intervention Description
2.Intramuscular injection at 5 x 10^7 pfu/ml at day 0. Intramuscular injection at 2.5 x 10^8 pfu/ml at day 0
Intervention Type
Biological
Intervention Name(s)
MVA-NP+M1
Intervention Description
3.Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0
Primary Outcome Measure Information:
Title
To assess the safety of a new influenza vaccine, MVA-NP+M1, when administered to healthy volunteers.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
To assess the cellular immune response generated by a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy adult aged 18 or over, no upper age limit Resident in or near Oxford for the duration of the vaccination study Able and willing (in the Investigators' opinions) to comply with all study requirements Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner For females, a negative pregnancy test on the day of vaccination and agreement to practice effective contraception for the duration of the study. Agreement to refrain from blood donation during the course of the study Written informed consent Exclusion Criteria: Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period Prior receipt of a recombinant MVA vaccine Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed) History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products Any history of anaphylaxis in reaction to vaccination History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) History of serious psychiatric condition Any chronic illness requiring ongoing or awaiting hospital specialist supervision, other than minor surgical procedures and follow up of surgery over 6 months prior to screening. Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units every week) Seropositive for hepatitis B surface antigen (HBsAg) Seropositive for hepatitis C virus (antibodies to HCV) For females, pregnancy, lactation or willingness/intention to become pregnant during the study Any other significant disease, disorder or finding, which, in the opinion of the Investigators, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis, as determined by the investigators.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian VS Hill, D.Phil FRCP
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34108964
Citation
Ferrara F, Del Rosario JMM, da Costa KAS, Kinsley R, Scott S, Fereidouni S, Thompson C, Kellam P, Gilbert S, Carnell G, Temperton N. Development of Lentiviral Vectors Pseudotyped With Influenza B Hemagglutinins: Application in Vaccine Immunogenicity, mAb Potency, and Sero-Surveillance Studies. Front Immunol. 2021 May 24;12:661379. doi: 10.3389/fimmu.2021.661379. eCollection 2021.
Results Reference
derived
PubMed Identifier
23118984
Citation
Antrobus RD, Lillie PJ, Berthoud TK, Spencer AJ, McLaren JE, Ladell K, Lambe T, Milicic A, Price DA, Hill AV, Gilbert SC. A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS One. 2012;7(10):e48322. doi: 10.1371/journal.pone.0048322. Epub 2012 Oct 31.
Results Reference
derived

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A Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NP+M1 in Healthy Adults

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