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

HIV Infection Clinical Trial

— MANON 02  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00219362
• Other study ID #: ORVACS 002
• Status: Completed
• Phase: Phase 2
• First received: September 16, 2005
• Last updated: November 24, 2009
• Start date: April 2004
• Est. completion date: September 2006

Study information

• Verified date: November 2009
• Source: Objectif Recherche Vaccins SIDA
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United States: Food and Drug AdministrationSpain: Spanish Agency of MedicinesGermany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: September 2006
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

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

• one injection of vCP1452 at W4, W8 and W20

• one injection of placebo at W0, W4, W8, W20 or at W4, W8,W20

Locations

Country	Name	City	State
France	Service des maladies infectieuses et tropicales, Hopital Pitié-Salpétrière, Pavillon Laveran	Paris
Germany	Klinikum der Johann Nolfgang Goethe Universitat Zentrum des Innerin Medizin	Frankfurt Am Main
Spain	Fundacio Irsi Caixa Retrovirology Laboratory, Hospital Universitari Germans	Badalona
Spain	Servicios de Infecciosos, Hospital y clinic Provincial	Barcelona
United States	Northwestern University Medical School	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Objectif Recherche Vaccins SIDA

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain, 

References & Publications (3)

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. Review. — View Citation

Autran B, Debré P, Walker B, Katlama C. Therapeutic vaccines against HIV need international partnerships. Nat Rev Immunol. 2003 Jun;3(6):503-8. Review. — View Citation

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 therapeuti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of the frequency of HIV-specific PBMC (CD4/CD8) at W24 (4 weeks after the last immunization)
Secondary	- 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 IFN?
Secondary	- 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 IFN?
Secondary	- Evaluation of the magnitude of CD4 and CD8 T cell response at W4, W6, W8, W12, W20, W24 in the study arms
Secondary	- Evaluation of the immune responses, HIV-specific PBMC and/or CD4 and/or CD8 T cells at W48
Secondary	- 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
Secondary	- Evaluation of the immune responses directed to vCP1452 in the study arms at all study point during the immunization phase
Secondary	- Percentage of patients who do not reach the restart therapy criteria from W24 to W48
Secondary	- Percentage of patients who remain off therapy at W48
Secondary	- Evaluation of the safety and tolerability of the vCP1452