Ignite Creation Date:
2024-05-05 @ 5:30 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00465465
Status:
COMPLETED
Last Update Posted:
2008-04-04
First Post:
2007-04-24
Brief Title:
A Study of 2 Doses of a New TB Vaccine MVA85A in Healthy Volunteers Previously Vaccinated With BCG
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
A Dose Selection Study Evaluating the Safety and Immunogenicity of 2 Different Doses of a New TB Vaccine MVA85A in Healthy Volunteers Who Have Previously Been Vaccinated With BCG
Status:
COMPLETED
Status Verified Date:
2008-03
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:
The dose of recombinant MVA used in the TB trials to date is relatively low compared with other trials using recombinant MVAs which have used up to 25 x 108pfu A Hill personal communication Having demonstrated safety and immunogenicity of 5 x 107pfu of MVA85A we now need to perform a dose optimization study prior to commencing larger scale Phase II and III studies in South Africa We will vaccinate 12 volunteers with a dose half a log lower than the dose we are currently using ie 107pfu MVA85A and 12 volunteers with a dose half a log higher ie 108pfu
Detailed Description:
MVA85A at a dose of 5 x 107pfu has been administered to 41 healthy volunteers in the UK and 17 healthy volunteers in The Gambia with no serious adverse events We have designed our Phase I studies to allow for a vaccination of volunteer groups sequentially with a step-wise increase in mycobacterial exposure in order to minimize the possibility of a Koch reaction 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 was described in patients with TB disease when Koch performed his original studies employing mycobacteria as a type of therapeutic vaccination It has now been demonstrated in the mouse model of therapeutic vaccination Taylor 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 We started these studies in healthy volunteers who were as mycobacterially naïve as possible They were skin test negative and Elispot negative for PPD ESAT 6 and CFP10 and had not had previously been vaccinated with BCG We have now completed studies in the UK vaccinating volunteers previously vaccinated with BCG McShane 2004 These volunteers are excluded if their Mantoux test is greater than 15 millimeters These studies are ongoing in The Gambia The group we are currently recruiting for on this increasing mycobacterial spectrum are healthy volunteers who are latently infected with Mtb
Decision matrix for selecting MVA85A dose
1 If reducing the dose of MVA85A results in reduced immunogenicity we could use either the 5x107 or 108 dose and would select the lower of these on the grounds of safety
2 If increasing the dose of MVA85A increases the incidence of side-effects we could use either the 5x107 or 107 dose and we would use the higher of these on the grounds of immunogenicity
3 If increasing the dose of MVA85A results in increased immunogenicity and no increase in side-effects we could use either the 5x107 or 108 dose in subsequent trials
4 If reducing the dose of MVA85A results in no reduction in immunogenicity we could use either the 107 or 5x107 dose in subsequent trials
5 If all three doses are equally safe and immunogenic we will use either the low or 5x107 dose
Decision matrix for selecting MVA85A dose
1 If reducing the dose of MVA85A results in reduced immunogenicity we could use either the 5x107 or 108 dose and would select the lower of these on the grounds of safety
2 If increasing the dose of MVA85A increases the incidence of side-effects we could use either the 5x107 or 107 dose and we would use the higher of these on the grounds of immunogenicity
3 If increasing the dose of MVA85A results in increased immunogenicity and no increase in side-effects we could use either the 5x107 or 108 dose in subsequent trials
4 If reducing the dose of MVA85A results in no reduction in immunogenicity we could use either the 107 or 5x107 dose in subsequent trials
5 If all three doses are equally safe and immunogenic we will use either the low or 5x107 dose
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