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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALVAC-HIV 4 injections | Experimental | Arm A: injection of ALVAC-HIV(vCP1452) for a total of 4 injections (W0, W4, W8, W20) |
|
| ALVAC-HIV 3 injections | Experimental | Arm B: injection of ALVAC-HIV(vCP1452) for a total of injections (W4, W8, W20) |
|
| Placebo - 4 injections | Placebo Comparator | Arm C1: injection of placebo for a total of 4 injections (W0, W4, W8, W20) |
|
| Placebo - 3 injections | Placebo Comparator | Arm C2: injection of placebo for a total of 3 injections (W4, W8, W20) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| one injection of vCP1452 at W0, W4, W8 and W20 | Biological |
| ||
| one injection of vCP1452 at W4, W8 and W20 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline of the frequency of HIV-specific PBMC (CD4/CD8) at W24 (4 weeks after the last immunization) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christine Katlama, MD | Services des maladies infectieuses et tropicales, Hopital de la Pitié-Salpétrière, Université Pierre et Marie Curie, INSERM U720 | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University Medical School | Chicago | Illinois | 60611 | United States | ||
| Service des maladies infectieuses et tropicales, Hopital Pitié-Salpétrière, Pavillon Laveran |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12776210 | Background | Autran B, Debre P, Walker B, Katlama C. Therapeutic vaccines against HIV need international partnerships. Nat Rev Immunol. 2003 Jun;3(6):503-8. doi: 10.1038/nri1107. | |
| 15285715 | Background | Autran B, Costagliola D, Murphy R, Katlama C. Evaluating therapeutic vaccines in patients infected with HIV. Expert Rev Vaccines. 2004 Aug;3(4 Suppl):S169-77. doi: 10.1586/14760584.3.4.s169. |
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| Biological |
|
| one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20 | Biological |
|
| - 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 |
| Paris |
| 75013 |
| France |
| Klinikum der Johann Nolfgang Goethe Universitat Zentrum des Innerin Medizin | Frankfurt am Main | 60590 | Germany |
| Fundacio Irsi Caixa Retrovirology Laboratory, Hospital Universitari Germans | Badalona | 08916 | Spain |
| Servicios de Infecciosos, Hospital y clinic Provincial | Barcelona | 08036 | Spain |
| 18580611 | Result | Autran B, Murphy RL, Costagliola D, Tubiana R, Clotet B, Gatell J, Staszewski S, Wincker N, Assoumou L, El-Habib R, Calvez V, Walker B, Katlama C; ORVACS Study Group. Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452). AIDS. 2008 Jul 11;22(11):1313-22. doi: 10.1097/QAD.0b013e3282fdce94. |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C064991 | N-(8-aminohexyl)-5-iodonaphthalene-1-sulfonamide |
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