Immunogenicity and Safety of 2 Schedules of ALVAC-HIV vCP1452 in Chronically HIV-Infected Patients

Study Overview
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Brief Summary
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Prior pilot studies have shown that four monthly injections of ALVAC-HIV (vCP1433) are immunogenic in 60% HIV-infected patients with a boosting effect obtained after 1 or 2 injections followed by a plateau or a decrease of these responses prior to interrupting therapy. The goal of the present study is to look for an improved vaccination schedule in terms of strength and duration of the HIV-specific immunity induced by the HIV-recombinant canary pox vector ALVAC-HIV (vCP1452) by testing a strategy of immunization involving a first series of two versus three monthly injections followed by a boost three months later.

Detailed Description
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Manon 02 is a phase II, multicentre, randomized, placebo-controlled study with 3 arms comprising 2 steps: Step I : Immunization phase from W0 to W24, on HAART The immunization will be administered by intramuscular injection : Arm A: one injection of vCP1452 at W0, W4, W8 and W20 + HAART, for a total of 4 injections Arm B: one injection of vCP1452 at W4, W8 and W20 + HAART, for a total of 3 injections Arm C: one injection of placebo at W0, W4, W8 and W20 + HAART, for a total of 4 injections or at W4, W8 and W20 + HAART, for a total of 3 injections Step II: Post immunization phase from W24 to W48, off HAART Discontinuation of antiretroviral therapy (ARV) from W24 to W48 : The ARV treatment interruption will be proposed at W24, 4 weeks after the last immunization, to patient who had completed their immunization phase and have CD4 cell counts > 350 cells/mm3 and HIV plasma RNA < 400 cp/ml. In order to be able to evaluate the capacity of the immune response to reduce the viral replication, a period of 16 weeks of interruption is recommended from W24 to W40. Resumption of antiretroviral therapy : From W24 to W40 : During this 16 weeks period, in case of a decline of CD4 cell counts below 250 cells/mm3 or of a loss of CD4 greater than 50% of the baseline value, HAART will be restarted. From W40 to W48 : HAART should be reintroduced if HIV-1 RNA levels > 50 000 cp/ml on 2 consecutive measurements at two weeks interval even if the CD4 counts are above 250 cells/mm3.

Official Title
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A Phase II, Randomized, Placebo-controlled Study to Evaluate the Immunogenicity and the Safety of 2 Schedules of an Homologous Prime-boost With the ALVAC-HIV vCP1452 in Chronically HIV-Infected Patients

Conditions
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HIV Infection

Intervention / Treatment
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* Biological: one injection of vCP1452 at W0, W4, W8 and W20
* Biological: one injection of vCP1452 at W4, W8 and W20
* Biological: one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HIV infection under potent antiretroviral therapy for more than 6 months with entry CD4+ counts > 350 cells/mm3 for at least 1 year plasma HIV RNA < 400 cp/ml for at least the last 6 months Contraception needed for women Exclusion Criteria: Antiretroviral therapy started with CD4 cell count > 400/mm3 Patients treated at time of primary HIV infection Patient with past AIDS defining event

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALVAC-HIV 4 injections<br>Arm A: injection of ALVAC-HIV(vCP1452) for a total of 4 injections (W0, W4, W8, W20) | Biological: one injection of vCP1452 at W0, W4, W8 and W20<br> <br> |
| Experimental: ALVAC-HIV 3 injections<br>Arm B: injection of ALVAC-HIV(vCP1452) for a total of injections (W4, W8, W20) | Biological: one injection of vCP1452 at W4, W8 and W20<br> <br> |
| Placebo Comparator: Placebo - 4 injections<br>Arm C1: injection of placebo for a total of 4 injections (W0, W4, W8, W20) | Biological: one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20<br> <br> |
| Placebo Comparator: Placebo - 3 injections<br>Arm C2: injection of placebo for a total of 3 injections (W4, W8, W20) | Biological: one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of the frequency of HIV-specific PBMC (CD4/CD8) at W24 (4 weeks after the last immunization) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Percentage of responders as defined by an increase of at least 0.7 log10 from baseline of the frequencies of HIV-specific PBMC and/or CD4 and/or CD8 T cells four weeks after the last immunization(W24) as measured by ELISpot IFNγ |  |  | 
| - Change from baseline of the frequency of HIV-specific PBMC and/or CD4 and/or CD8 T cells at week 4, 6, 8, 12, 20 and 24 in the study arms as measured by ELISpot IFNγ |  |  | 
| - Evaluation of the magnitude of CD4 and CD8 T cell response at W4, W6, W8, W12, W20, W24 in the study arms |  |  | 
| - Evaluation of the immune responses, HIV-specific PBMC and/or CD4 and/or CD8 T cells at W48 |  |  | 
| - Percentage of patients who generate a primary immune response against the artificial pol/nef sequences present in the vaccine but not in the HIV strain |  |  | 
| - Evaluation of the immune responses directed to vCP1452 in the study arms at all study point during the immunization phase |  |  | 
| - Percentage of patients who do not reach the restart therapy criteria from W24 to W48 |  |  | 
| - Percentage of patients who remain off therapy at W48 |  |  | 
| - Evaluation of the safety and tolerability of the vCP1452 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1 infection, therapeutic vaccine, Treatment Experienced