Safety and Immunological Response of a Boosting Dose of MVA-B in Healthy Volunteers After 4 Years of Receiving MVA-B

Study Overview
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Brief Summary
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24 healthy male and female volunteers who are at low risk of HIV infection and entered into the RISVAC02 study and were randomly allocated to receive 3 intramuscular injections of MVA-B at weeks 0, 4 and 16 will receive a boosting dose 4 years thereafter. Participants will attend one of two clinical centres on at least 5 occasions over 16 weeks. These visits will comprise: Screening Trial entry and boosting immunisation Early follow-up after immunisation Follow-up x 2 including the final visit Participants will have blood and urine collected, and receive 1 immunisation. They will be counselled prior to and following a HIV test, and given health education on prevention of sexually transmitted infections including HIV. T The two centres which participate are: Hospital Clinic, Barcelona and Hospital Gregorio Marañón, Madrid The primary objective is to explore the safety and immunogenicity of MVA-B.

Official Title
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Safety and Immunological Response of a Boosting Dose of MVA-B in Healthy Volunteers After 4 Years of Receiving MVA-B

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Experimental


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female age between 18 and 55 years on the day of screening available for follow-up for the duration of the study (52 weeks from screening) able to give written informed consent at low risk of HIV and willing to remain so for the duration of the study low risk of HIV infection defined as: no history of injecting drug use in the previous ten years no gonorrhoea or syphilis in the last six months no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months no unprotected anal intercourse in the last six months no unprotected vaginal intercourse outside a relationship with a regular known/presumed HIV negative partner in the last six months willing to undergo a HIV test willing to undergo a genital infection screen if heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable contraceptive; IUCD; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination if heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination Exclusion Criteria: positive for hepatitis B surface antigen, hepatitis C antibody, antibody responses to vaccinia or serology indicating active syphilis requiring treatment pregnant or lactating clinically relevant abnormality on history or examination including history of grand-mal epilepsy, severe eczema, immunodeficiency or use of immunosuppressives in preceding 3 months receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment receipt of blood products or immunoglobin within 4 months of screening participation in another trial of a medicinal product, completed less than 30 days prior to enrolment history of severe local or general reaction to vaccination defined as local: extensive, indurated redness and swelling involving most of the front-lateral thigh or the major circumference of the arm, not resolving within 72 hours general: fever >= 39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal HIV 1/2 positive or indeterminate on screening positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment grade 1 routine laboratory parameters unlikely to comply with protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main<br>MVA HIV-B | Biological: Experimental<br>* Biological/Vaccine: MVA-B Modified Pox virus, strain MVA clade -B (expressing HIV-1 Bx08gp120 and IIIB gagpolnef) -  1 x 10e8 pfu/ml 3 immunisations at week 0, 4 and 16<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local adverse event | Grade 3 or above local adverse event (pain, cutaneous reactions including induration) | 12 weeks | 
| Grade 3 or above systemic adverse event | Grade 3 or above systemic adverse event (temperature, chills, headache, nausea, vomiting, malaise, and myalgia) | 12 weeks | 
| Grade 3 or above other clinical or laboratory adverse event | Grade 3 or above other clinical or laboratory adverse event confirmed at examination or on repeat testing respectively | 12 weeks | 
| Event attributable to vaccine leading to discontinuation | Any event attributable to vaccine leading to discontinuation of the immunisation regimen | 12 weeks | 
| Primary immunogenicity parameters | The primary immunogenicity parameters will be quantitative or present/absent, and are cellular responses - CD8/CD4+ T cell responses (ELISPOT) at week 2, 4 and 12 following the immunisations | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All grade 1 and 2 adverse events |  | 28 days of vaccination | 
| Antibody responses | binding titration to the construct MVAB binding titration to and neutralisation of vaccinia | 12 weeks | 
| cellular responses | CD8/CD4+ T cell responses (ELISPOT) at week 0 intracellular cytokine analysis at week 0, 2, 4 and 12 | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low risk HIV infection, HIV Seronegativity, HIV Preventive Vaccine