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

This study has been completed.
Sponsor:
Collaborator:
Wellcome Trust
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00993083
First received: October 8, 2009
Last updated: August 10, 2011
Last verified: January 2011
  Purpose

This is a Phase IIa open label, non placebo controlled, non-randomised controlled challenge study. The primary objective of this study is to assess the safety of a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.

Initially two volunteers will be vaccinated and challenged with Influenza, followed by vaccination of a further 12 volunteers and an Influenza challenge of those 12 along with 12 non-vaccinated controls.


Condition Intervention Phase
Influenza
Biological: MVA-NP+M1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase IIA Study to Assess the Safety and Efficacy of a New Influenza Candidate Vaccine MVA-NP+M1 In Healthy Adults

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Safety of a new Influenza vaccine, MVA-NP+M1, when administered to healthy volunteers [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Cellular immune response generated by a new influenza vaccine MVA- NP+M1 when administered as a single dose to healthy adults. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: June 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccinated
14 volunteers (2 in lead safety group and 12 in main study group) to receive MVA-NP+M1 via the IM route. Volunteers will then be challenged with Influenza 30 days post vaccination.
Biological: MVA-NP+M1
Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0
No Intervention: Control
12 volunteers who will not receive vaccine but will also be challenged with Influenza on day 30

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or females aged 18 - 45 years
  2. HI titre of less than 10
  3. In general good health determined by a screening evaluation (medical history, physical examination, vital signs electrocardiogram (ECG) and clinical safety laboratory tests). ECG and spirometry will be performed at entry into quarantine rather than at screening visit
  4. Females should fulfil the following criteria: (i) not pregnant or breastfeeding for the duration of the study and (ii) agree to use a reliable form of contraception for the duration of the study if sexually active
  5. Negative HBsAg, HIV and HCV antibody screen
  6. Negative class A drugs of abuse screen
  7. Have not been vaccinated for Influenza virus in the current season or had a known influenza virus infection in the current season
  8. Give written informed consent to participate
  9. Willingness to remain in isolation during the challenge phase of the study and to comply with all study requirements
  10. Willing and able to communicate with the Investigator and understand the requirements of the study

Exclusion Criteria:

  1. Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use of an IMP during the study period
  2. Prior receipt of a recombinant MVA vaccine (vaccinees only)
  3. Administration of immunoglobulins and/or any blood products within the three months preceding date of enrolment.
  4. 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
  5. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products. Any allergy to eggs or egg products
  6. Any history of anaphylaxis in reaction to vaccination
  7. Current cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  8. Serious current psychiatric condition
  9. Any other chronic illness requiring hospital specialist supervision
  10. Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units every week)
  11. 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.
  12. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis (see Table 1. Values outside the stated limits of Table 1 need written comment by a physician if considered clinically insignificant).
  13. Venous access inadequate for phlebotomy demands of the study
  14. Clinically significant abnormality on ECG
  15. History since age 13 of asthma of any aetiology
  16. Smokers who are unwilling or unable to desist for the duration of the inpatient challenge component of the study
  17. Any anatomic or neurologic abnormality impairing the gag reflex or associated with a risk of aspiration
  18. Presence of febrile illness or symptoms of upper respiratory tract infection on the day of vaccination (vaccination would be deferred)
  19. Presence of febrile illness or symptoms suggestive of influenza between admission for influenza challenge and administration of the challenge inoculum
  20. Use of inhaled, topical or systemic steroids in the six months preceding date of enrolment other than occasional use of cutaneous steroid if considered clinically irrelevant to the study by the Investigator..
  21. Donation of blood or blood products within 7 days before study entry or at any time during the study
  22. Donation of plasma within 7 days of study entry
  23. Anti-'flu antibody titre of 10 or greater
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993083

Locations
United Kingdom
Wellcome Trust Clinical Research Facility, University of Southampton
Southampton, Hampshire, United Kingdom, SO16 6YD
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Wellcome Trust
Investigators
Principal Investigator: Adrian VS Hill, DPhil University of Oxford
  More Information

No publications provided by University of Oxford

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor Adrian Hill, University of Oxford
ClinicalTrials.gov Identifier: NCT00993083     History of Changes
Other Study ID Numbers: Flu002
Study First Received: October 8, 2009
Last Updated: August 10, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
Influenza
Vaccine

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 16, 2014