Immunogenicity and Safety of 2 Schedules of ALVAC-HIV vCP1452 in Chronically HIV-Infected Patients (MANON 02)

Objectif Recherche Vaccins SIDA

Status and phase: Completed; Phase 2

Conditions: HIV Infection

Treatments: Biological: one injection of vCP1452 at W0, W4, W8 and W20; Biological: one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20; Biological: one injection of vCP1452 at W4, W8 and W20

Study type: Interventional

Funder types: Other

Identifiers

NCT00219362

ORVACS 002

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 65 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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65 participants in 4 patient groups, including a placebo group

ALVAC-HIV 4 injections

Experimental group

Description:

Arm A: injection of ALVAC-HIV(vCP1452) for a total of 4 injections (W0, W4, W8, W20)

Treatment:

Biological: one injection of vCP1452 at W0, W4, W8 and W20

ALVAC-HIV 3 injections

Experimental group

Description:

Arm B: injection of ALVAC-HIV(vCP1452) for a total of injections (W4, W8, W20)

Treatment:

Biological: one injection of vCP1452 at W4, W8 and W20

Placebo - 4 injections

Placebo Comparator group

Description:

Arm C1: injection of placebo for a total of 4 injections (W0, W4, W8, W20)

Treatment:

Biological: one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20

Placebo - 3 injections

Placebo Comparator group

Description:

Arm C2: injection of placebo for a total of 3 injections (W4, W8, W20)

Treatment:

Biological: one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20