Ignite Creation Date:
2024-05-05 @ 5:18 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00423839
Status:
COMPLETED
Last Update Posted:
2007-01-18
First Post:
2007-01-17
Brief Title:
A Phase I Study of the Safety and Immunogenicity of MVA85A in Healthy Gambian Volunteers
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
A Phase I Study of the Safety and Immunogenicity of MVA85A in Healthy Gambian Volunteers
Status:
COMPLETED
Status Verified Date:
2006-12
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:
A Phase I study of the Safety and immunogenicity of MVA85A in healthy Gambian volunteers
Detailed Description:
Study Design The study is a non-randomized clinical trial Twelve volunteers will be recruited They would be given 5x107 pfu of the MVA85A vaccine intradermally The subjects will be required to stay in the unit for an hour after the vaccination Local and systemic adverse events would be recorded Blood samples will be taken at the screening visit day of immunisation 1 week after the vaccination then at 2 4 8 12 and 24 weeks after the vaccination
Screening
Details of the study will be carefully discussed with the subjects and informed consent approved by the combined MRCGambian government ethics committee prior to any study-related evaluations being performed The subjects that agree to enroll and have signed consent documentation will be assessed at the AFTBVAC clinic at MRC
Entry
Subjects will be recruited at the MRC AFTBVAC clinic Subjects will be screened in the eight weeks prior to entering the study The screen will consist of checking subject eligibility and a full physical examination The following will be carried out height weight vital signs haematology haemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins Mantoux test ELISPOT Chest X-ray anti-vaccinia antibodies anti-HBV antibodies anti-HIV antibodies urinalysis All chest X-rays will be reviewed by two clinicians to confirm no radiological sign of Tuberculosis
Evaluations during study Scheduled follow-up
Vaccination Day 0 after a pysician has confirmed that the volunteers are ESAT-6 and CFP-10 nagative The following assessments will be performed pre-dosing vital signs 20 minutes pre-dose and blood samples collected for heamatology haemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins and immunological assays Provided vital signs are is satisfactory subjects will receive the first vaccination Subjects will have a dressing applied over the injection site which will remain for at least one hour after the vaccination Post vaccination vital signs will be taken at 30 and 60 minutes Any adverse events AEs noted by the study personnel or described by the volunteer will be documented Concomitant medication given will be documented The volunteer will remain at the clinical area for one hour following vaccination and will then be allowed to return home
Day 1 and 2 On the first and second day after vaccination subjects will be visited at home by a field worker or they will return to the clinical area The injection site will be examined and the subjects will be questioned for AEs and use of any concomitant medications
Day 7 Subjects will be visited at home by a field worker or they will return to the clinical area Vital sign assessments will be performed Blood samples will be taken for haematologyhaemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins and immunological assays The injection site will be examined and the subjects will be questioned for AEs and concomitant medications
At day 14 28 56 84 and 189 subjects will return to the clinical area Vital sign assessments will be performed Blood samples will be taken prior to dosing for haematology haemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins and immunological assays The injection site will be examined and the subjects will be questioned for AEs and concomitant medications Day 22 and 23 On the first and second day after vaccination a field worker will visit subjects at home or they will return to the clinical area The injection site will be examined and the subjects will be questioned for AEs and concomitant medications
Post study Evaluations
The injection site will be examined and the subjects asked about AEs It is possible that they will be asked in the future to provide samples for genetic studies
DATA COLLECTION AND MONITORING AND ADVERSE EXPERIENCE REPORTING
Records to be kept and a regulatory folder will contain
SCC document Project Management plan Protocol with appendices Letter of ethical approval Information sheets and blank forms Signed consent forms for each subject
All filled in paper forms will be filed Individual medical records will be filed together
All data on the Case Report Forms CRF must be legibly recorded in blue or black ink or typed A correction should be made by striking through the incorrect entry with a single line and entering the correct information adjacent to it The correction must be initialed and dated by the investigator or a designated qualified individual
Any requested information that is not obtained as specified in the protocol should have an explanation noted on the CRF as to why the required information was not obtained
Role of Data Management
The Data manager will be responsible for receiving entering querying analysing and storing the data which accrues from the study He will be responsible for linking the epidemiological and clinical data from the field and the clinic with the laboratory data from the immunology microbiology haematology and genetics laboratories
Adverse Events AE Reporting
Adverse events however minor will be recorded as observed by the Investigators or as volunteered by the subject Full details will be documented in the CRF whether or not the Investigator or his deputies consider the event to be related to the trial substance
Serious Adverse Events SAE Reporting
Serious adverse events SAEs that occur during the study or within six months of the final vaccination will be notified immediately within 24 hours by telephone to the Safety Monitor Ethics Committee collaborators and funding agency
Serious adverse event are defined as an event that
results in death
is life-threatening ie the subject was at risk of death at the time of the event
requires or prolongs in-patient hospitalization
results in persistent or significant disabilityincapacity
is a congenital anomalybirth defect
is a cancer
Note
Proven malaria events will not be included as an SAE
Minimum details to be given in a telephone report are
Name of reporting doctor and contact telephone number
Study number
Nature of adverse event
Subject details number initials sex date of birth weight and age
Date and time of event
Date and time of MVA85A administration and dose
Other drug history
Other relevant history
Outcome
Causality
The event will be documented on the SAE page of the CRF and reported to the Safety Monitor Ethics Committee Collaborators and funding agency as appropriate Other adverse events will be graded After the ethics committees response to the SAE is received the Principal Investigator Clinical Monitor and available co-investigators will meet to determine the future plan for the study which could involve amending the protocol discontinuing the vaccinations or continuing unchanged for the other volunteers
STATISTICAL CONSIDERATIONS
General Design Issues
A total of 12 subjects will be sufficient to provide descriptive data As some of the subjects may drop out of the study 12 subjects However only 10 individuals will be given the vaccine
Outcomes of interest
Safety of the Vaccine
This will be determined by the degree and number of adverse events reported
Immunogenicity of this vaccine
It is expected that the vaccine will stimulate T cell responses which will be measured by interferon -gamma Elispot assays
Sample Size and Accrual
Formal sample sizing calculations have not been performed but it is believed that the sample size of 10 subjects will be sufficient for this purpose
No attempt will be made in the study to conceal the allocation group of the subjects either from the subjects themselves the investigators or laboratory personnel
Monitoring and Analysis
The data manager will be responsible for monitoring the trial This will include confirming the existence of the appropriate documents in the regulatory folder and of source documents for all entered data He would also assess the consistency of data The data manager will be responsible for data entry and for initial analysis of the results
The main analyses will be descriptive and comparative
HUMAN SUBJECTS
Institutional Review Board IRB Review and Informed Consent
The study has been approved by the joint MRC Gambia government ethical committee Written informed consent will be obtained from the subject or parent legal guardian or person with power of attorney for subjects who cannot consent for themselves such as those below the legal age The subjects assent must also be obtained if he or she is able to understand the nature significance and risks associated with the study The informed consent will describe the purpose of the study the procedures to be followed and the risks and benefits of participation A signed copy of the consent form will be given to the subject or parent or legal guardian
Subject Confidentiality
All records will be kept in a secure place All data on computer files will have restricted access Clinical information will not be released without written permission of the subject except as necessary for monitoring
Screening
Details of the study will be carefully discussed with the subjects and informed consent approved by the combined MRCGambian government ethics committee prior to any study-related evaluations being performed The subjects that agree to enroll and have signed consent documentation will be assessed at the AFTBVAC clinic at MRC
Entry
Subjects will be recruited at the MRC AFTBVAC clinic Subjects will be screened in the eight weeks prior to entering the study The screen will consist of checking subject eligibility and a full physical examination The following will be carried out height weight vital signs haematology haemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins Mantoux test ELISPOT Chest X-ray anti-vaccinia antibodies anti-HBV antibodies anti-HIV antibodies urinalysis All chest X-rays will be reviewed by two clinicians to confirm no radiological sign of Tuberculosis
Evaluations during study Scheduled follow-up
Vaccination Day 0 after a pysician has confirmed that the volunteers are ESAT-6 and CFP-10 nagative The following assessments will be performed pre-dosing vital signs 20 minutes pre-dose and blood samples collected for heamatology haemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins and immunological assays Provided vital signs are is satisfactory subjects will receive the first vaccination Subjects will have a dressing applied over the injection site which will remain for at least one hour after the vaccination Post vaccination vital signs will be taken at 30 and 60 minutes Any adverse events AEs noted by the study personnel or described by the volunteer will be documented Concomitant medication given will be documented The volunteer will remain at the clinical area for one hour following vaccination and will then be allowed to return home
Day 1 and 2 On the first and second day after vaccination subjects will be visited at home by a field worker or they will return to the clinical area The injection site will be examined and the subjects will be questioned for AEs and use of any concomitant medications
Day 7 Subjects will be visited at home by a field worker or they will return to the clinical area Vital sign assessments will be performed Blood samples will be taken for haematologyhaemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins and immunological assays The injection site will be examined and the subjects will be questioned for AEs and concomitant medications
At day 14 28 56 84 and 189 subjects will return to the clinical area Vital sign assessments will be performed Blood samples will be taken prior to dosing for haematology haemoglobin packed cell volume white cell counts platelets blood film for malaria parasites serum chemistry electrolytes and creatinine liver enzymes serum bilirubin and proteins and immunological assays The injection site will be examined and the subjects will be questioned for AEs and concomitant medications Day 22 and 23 On the first and second day after vaccination a field worker will visit subjects at home or they will return to the clinical area The injection site will be examined and the subjects will be questioned for AEs and concomitant medications
Post study Evaluations
The injection site will be examined and the subjects asked about AEs It is possible that they will be asked in the future to provide samples for genetic studies
DATA COLLECTION AND MONITORING AND ADVERSE EXPERIENCE REPORTING
Records to be kept and a regulatory folder will contain
SCC document Project Management plan Protocol with appendices Letter of ethical approval Information sheets and blank forms Signed consent forms for each subject
All filled in paper forms will be filed Individual medical records will be filed together
All data on the Case Report Forms CRF must be legibly recorded in blue or black ink or typed A correction should be made by striking through the incorrect entry with a single line and entering the correct information adjacent to it The correction must be initialed and dated by the investigator or a designated qualified individual
Any requested information that is not obtained as specified in the protocol should have an explanation noted on the CRF as to why the required information was not obtained
Role of Data Management
The Data manager will be responsible for receiving entering querying analysing and storing the data which accrues from the study He will be responsible for linking the epidemiological and clinical data from the field and the clinic with the laboratory data from the immunology microbiology haematology and genetics laboratories
Adverse Events AE Reporting
Adverse events however minor will be recorded as observed by the Investigators or as volunteered by the subject Full details will be documented in the CRF whether or not the Investigator or his deputies consider the event to be related to the trial substance
Serious Adverse Events SAE Reporting
Serious adverse events SAEs that occur during the study or within six months of the final vaccination will be notified immediately within 24 hours by telephone to the Safety Monitor Ethics Committee collaborators and funding agency
Serious adverse event are defined as an event that
results in death
is life-threatening ie the subject was at risk of death at the time of the event
requires or prolongs in-patient hospitalization
results in persistent or significant disabilityincapacity
is a congenital anomalybirth defect
is a cancer
Note
Proven malaria events will not be included as an SAE
Minimum details to be given in a telephone report are
Name of reporting doctor and contact telephone number
Study number
Nature of adverse event
Subject details number initials sex date of birth weight and age
Date and time of event
Date and time of MVA85A administration and dose
Other drug history
Other relevant history
Outcome
Causality
The event will be documented on the SAE page of the CRF and reported to the Safety Monitor Ethics Committee Collaborators and funding agency as appropriate Other adverse events will be graded After the ethics committees response to the SAE is received the Principal Investigator Clinical Monitor and available co-investigators will meet to determine the future plan for the study which could involve amending the protocol discontinuing the vaccinations or continuing unchanged for the other volunteers
STATISTICAL CONSIDERATIONS
General Design Issues
A total of 12 subjects will be sufficient to provide descriptive data As some of the subjects may drop out of the study 12 subjects However only 10 individuals will be given the vaccine
Outcomes of interest
Safety of the Vaccine
This will be determined by the degree and number of adverse events reported
Immunogenicity of this vaccine
It is expected that the vaccine will stimulate T cell responses which will be measured by interferon -gamma Elispot assays
Sample Size and Accrual
Formal sample sizing calculations have not been performed but it is believed that the sample size of 10 subjects will be sufficient for this purpose
No attempt will be made in the study to conceal the allocation group of the subjects either from the subjects themselves the investigators or laboratory personnel
Monitoring and Analysis
The data manager will be responsible for monitoring the trial This will include confirming the existence of the appropriate documents in the regulatory folder and of source documents for all entered data He would also assess the consistency of data The data manager will be responsible for data entry and for initial analysis of the results
The main analyses will be descriptive and comparative
HUMAN SUBJECTS
Institutional Review Board IRB Review and Informed Consent
The study has been approved by the joint MRC Gambia government ethical committee Written informed consent will be obtained from the subject or parent legal guardian or person with power of attorney for subjects who cannot consent for themselves such as those below the legal age The subjects assent must also be obtained if he or she is able to understand the nature significance and risks associated with the study The informed consent will describe the purpose of the study the procedures to be followed and the risks and benefits of participation A signed copy of the consent form will be given to the subject or parent or legal guardian
Subject Confidentiality
All records will be kept in a secure place All data on computer files will have restricted access Clinical information will not be released without written permission of the subject except as necessary for monitoring
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