Ignite Creation Date:
2024-05-05 @ 5:35 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00480454
Status:
COMPLETED
Last Update Posted:
2010-02-09
First Post:
2007-05-30
Brief Title:
Safety Immunogenicity and Impact of MVA85A on the Immunogenicity of the EPI Vaccines
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
An Open Randomized Dose Selection Study Evaluating the Safety Immunogenicity and Impact of a TB Vaccine MVA85A on the Immunogenicity of EPI Vaccines Administered Simultaneously to Healthy Infants Previously Vaccinated With BCG
Status:
COMPLETED
Status Verified Date:
2010-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is preliminary to proving that this vaccine could protect against tuberculosis in humans Although there is no proven data to show that infants will benefit directly from participation in this study by being protected against TB MVA85A protection of mice guinea pigs and monkeys against tuberculosis is encouraging It is hoped that the information gained from this study will contribute to the development of a safe and effective TB vaccine for HIV negative and positive individuals Participants in this study will benefit by having information about their general health status and the rigorous follow up visit that could enhance early detection and management of medical conditions that might arise in the course of the study
Detailed Description:
Over the last 3 years Phase I studies with MVA85A allowed for sequential vaccination of volunteer groups with a step-wise increase in mycobacterial exposure to minimize the possibility of a Koch reaction Trials were also conducted sequentially in the UK and The Gambia as there is a greater degree of exposure to both environmental mycobacteria and Mtb in The Gambia A Koch reaction describes the development of immunopathology in a person or animal with tuberculosis when an exaggerated immune response to Mtb is stimulated It has now been demonstrated in the mouse model of therapeutic vaccination Taylor et al 2003 Available animal data suggest that these reactions do not occur in mice latently infected with Mtb suggesting that such reactions may correlate with high bacterial load and that the Koch phenomenon may not pose a problem for vaccination of healthy albeit latently infected humans Taylor et al 2003
In the UK 14 mycobacterially and BCG naïve healthy volunteers were vaccinated twice with 5 x 107pfu MVA85A administered intradermally at 3 week intervals MVA85A was found to be safe and well tolerated A single vaccination with MVA85A induced remarkably high levels of specific effector T cell responses 1 week after vaccination mean γ IFN Elispot response to PPD was 460 spots per million PBMC MVA85A was also safe in 17 volunteers vaccinated with BCG in the previous 05-37 years The safety profile of MVA85A in these 17 volunteers was the same as in the BCG naïve group Interestingly these 17 volunteers showed even higher peak levels of antigen specific T cells mean response to PPD was 917 spots per million PBMC 1 week post-vaccination than those immunized with MVA85A alone Perhaps more importantly for the induction of T cell memory these volunteers who were previously BCG vaccinated maintained significantly higher levels of antigen specific T cells after MVA85A for up to 24 weeks after vaccination when compared to those volunteers vaccinated with either BCG or MVA85A alone McShane et al 2004 The next trial in the UK looked at the boosting efficacy of MVA85A when administered one month after BCG vaccination 10 healthy BCG naïve volunteers were vaccinated with BCG and one month later were boosted with MVA85A Safety and boosting efficacy was comparable to the previous trial where the interval between BCG and MVA85A was 05-37 years
232 Gambian studies Following the success of the trials with MVA85A in the UK a collaboration with the MRC unit in The Gambia was initiated MVA85A was first evaluated in Phase I clinical trials in BCG naïve subjects n 11 and subsequently in BCG primed subjects n10 In these studies the safety and immunogenicity profile is comparable to that seen in the UK studies In both the UK and The Gambian studies MVA85A induces 5-10 fold higher immune responses than any other recombinant MVA in clinical trials The most likely explanation for this is that the volunteers have some weak pre-existing anti-mycobacterial immunity induced by exposure to environmental mycobacteria and this is being boosted by vaccination with MVA85A When MVA85A is administered to BCG naïve subjects in the Gambia the magnitude and kinetics of response resemble the BCG primed group in the UK a finding that is likely to represent a greater degree of environmental priming in tropical climates
Taken together over 600 people including HIV positive and over 250 Gambian adults and children have now been immunised with various recombinant MVA investigational vaccines including constructs expressing malaria HIV hepatitis B and melanoma antigens without significant adverse reactions Hill unpublished data Furthermore 190 children aged 1-5 years were vaccinated with a recombinant MVA expressing a malarial antigen in 2006 with no vaccine related SAEs Hill personal communication This safety data now allows for progression to testing MVA85A in a phase II study in infants who have been vaccinated with BCG in a Gambian population which may include low numbers of latently Mtb infected and HIV positive children
It is important to test the safety immunogenicity and possible interference detrimental none or beneficial with other EPI vaccines of the MVA85A vaccine in such a group which is one of the potential target populations for a large-scale efficacy study Also the effects of simultaneous EPI vaccine administration on the immunogenicity of MVA85A need to be evaluated
In the UK 14 mycobacterially and BCG naïve healthy volunteers were vaccinated twice with 5 x 107pfu MVA85A administered intradermally at 3 week intervals MVA85A was found to be safe and well tolerated A single vaccination with MVA85A induced remarkably high levels of specific effector T cell responses 1 week after vaccination mean γ IFN Elispot response to PPD was 460 spots per million PBMC MVA85A was also safe in 17 volunteers vaccinated with BCG in the previous 05-37 years The safety profile of MVA85A in these 17 volunteers was the same as in the BCG naïve group Interestingly these 17 volunteers showed even higher peak levels of antigen specific T cells mean response to PPD was 917 spots per million PBMC 1 week post-vaccination than those immunized with MVA85A alone Perhaps more importantly for the induction of T cell memory these volunteers who were previously BCG vaccinated maintained significantly higher levels of antigen specific T cells after MVA85A for up to 24 weeks after vaccination when compared to those volunteers vaccinated with either BCG or MVA85A alone McShane et al 2004 The next trial in the UK looked at the boosting efficacy of MVA85A when administered one month after BCG vaccination 10 healthy BCG naïve volunteers were vaccinated with BCG and one month later were boosted with MVA85A Safety and boosting efficacy was comparable to the previous trial where the interval between BCG and MVA85A was 05-37 years
232 Gambian studies Following the success of the trials with MVA85A in the UK a collaboration with the MRC unit in The Gambia was initiated MVA85A was first evaluated in Phase I clinical trials in BCG naïve subjects n 11 and subsequently in BCG primed subjects n10 In these studies the safety and immunogenicity profile is comparable to that seen in the UK studies In both the UK and The Gambian studies MVA85A induces 5-10 fold higher immune responses than any other recombinant MVA in clinical trials The most likely explanation for this is that the volunteers have some weak pre-existing anti-mycobacterial immunity induced by exposure to environmental mycobacteria and this is being boosted by vaccination with MVA85A When MVA85A is administered to BCG naïve subjects in the Gambia the magnitude and kinetics of response resemble the BCG primed group in the UK a finding that is likely to represent a greater degree of environmental priming in tropical climates
Taken together over 600 people including HIV positive and over 250 Gambian adults and children have now been immunised with various recombinant MVA investigational vaccines including constructs expressing malaria HIV hepatitis B and melanoma antigens without significant adverse reactions Hill unpublished data Furthermore 190 children aged 1-5 years were vaccinated with a recombinant MVA expressing a malarial antigen in 2006 with no vaccine related SAEs Hill personal communication This safety data now allows for progression to testing MVA85A in a phase II study in infants who have been vaccinated with BCG in a Gambian population which may include low numbers of latently Mtb infected and HIV positive children
It is important to test the safety immunogenicity and possible interference detrimental none or beneficial with other EPI vaccines of the MVA85A vaccine in such a group which is one of the potential target populations for a large-scale efficacy study Also the effects of simultaneous EPI vaccine administration on the immunogenicity of MVA85A need to be evaluated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None