A Study to Evaluate the Safety of the HIV-1 Vaccine MVA-B in Chronic HIV-1 Infected Patients Successfully Treated With HAART

Study Overview
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Brief Summary
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30 treated chronic HIV-1 infected patients with CD4+ cell counts above 450 cells/ mm3 will be randomized 1:2 to receive placebo (n=10) or vaccine (n=20) at week 0, 4 and 16 and will be observed at the Investigation Unit of the study site for one hour following vaccination. At week 24 they will stop their HAART until the end of the study.

Official Title
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A Double-blind Phase I Study to Evaluate the Safety of the HIV-1 Vaccine MVA-B in Chronic HIV-1 Infected Patients Successfully Treated With HAART

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Vaccination
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is ≥ 18 years of age; Voluntarily signed informed consent; Patient is male, or female with negative pregnancy test prior to enrolment; Patient has a proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA); Patient must be on stable treatment with HAART for at least 6 months (HAART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral agents*); Mean of all measured CD4+ cell counts during the 6 months prior to the start of HAART must be above or equal to 200 cells/ mm3 Current CD4+ cell count must be at least 450 cells/ mm3; HIV-RNA must be below 50 copies/ mL for the last 6 months prior to inclusion, during at least two measurements (occasional so called 'blips' up to 50 copies/mL are permitted); Patient is one of the following: not sexually active, or a heterosexually active female, agreeing to use condoms with her partner from 14 days prior to the first vaccination until 4 months after the last, even though using another method of contraception, and willing to undergo pregnancy tests during screening and prior to each vaccination, or a male, agreeing to use condoms with his partner from the day of the first vaccination until 4 months after the last vaccination. Exclusion Criteria: Treatment with a non-HAART regimen of antiretroviral agents prior to the start of HAART; History of a CDC class C event (see Appendix); Interruption of HAART during the course of the study which is expected at the time of inclusion; History of exposure <20 years ago to any poxvirus based vaccine; Patient is female and has a positive pregnancy test or the wish of pregnancy: Active opportunistic infection, or any active infection or malignancy within 30 days prior to screening visit; Therapy with immunomodulatory agents, including cytokines (e.g. IL2) and gamma globulin, or cytostatic chemotherapy within 90 days prior to screening visit; History of allergy to any vaccine component; Use of anti-coagulant medication; Use of any investigational drug during the 90 days prior to study entry; Previous failure to antiretroviral and/or mutations conferring genotypic resistance to antiretroviral therapy Any other condition which, in the opinion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine group<br>Modified Pox virus, strain MVA clade -B (expressing HIV-1 Bx08gp120 and IIIB gagpolnef) (MVA HIV-B) | Drug: Vaccination<br>* 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>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 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 |
| --- | --- | --- |
| primary safety parameters | Grade 3 or above local adverse event (pain, cutaneous reactions including induration) Grade 3 or above systemic adverse event (temperature, chills, headache, nausea, vomiting, malaise, and myalgia) Grade 3 or above other clinical or laboratory adverse event confirmed at examination or on repeat testing respectively Any event attributable to vaccine leading to discontinuation of the immunisation regimen | week 8 | 
| Primary immunogenicity parameters | Cellular responses - CD8/CD4+ T cell responses (ELISPOT) | After each inmunisation and at weeks 6-8 and 18-20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All grade 1 and 2 adverse events |  | week 8 | 
| Viral load rebound | After HAART interruption compared between both arms and with baseline viral load before any medication in each arm | week 48 | 
| Antibody responses | binding titration to the construct MVAB binding titration to and neutralisation of vaccinia | 48 weeks | 
| Cellular responses | Intracellular cytokine analysis | Week 6 and 18 | 

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