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

November 24, 2009 updated by: Objectif Recherche Vaccins SIDA

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Service des maladies infectieuses et tropicales, Hopital Pitié-Salpétrière, Pavillon Laveran
  • Germany
      • Frankfurt Am Main, Germany, 60590
        • Klinikum der Johann Nolfgang Goethe Universitat Zentrum des Innerin Medizin
  • Spain
      • Badalona, Spain, 08916
        • Fundacio Irsi Caixa Retrovirology Laboratory, Hospital Universitari Germans
      • Barcelona, Spain, 08036
        • Servicios de Infecciosos, Hospital y clinic Provincial
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ALVAC-HIV 4 injections
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
Experimental: ALVAC-HIV 3 injections
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
Placebo Comparator: Placebo - 4 injections
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
Placebo Comparator: Placebo - 3 injections
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
- 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Objectif Recherche Vaccins SIDA

Investigators

  • Study Chair: Christine Katlama, MD, Services des maladies infectieuses et tropicales, Hopital de la Pitié-Salpétrière, Université Pierre et Marie Curie, INSERM U720

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Primary Completion (Actual)

November 1, 2005

Study Completion (Actual)

September 1, 2006

Study Registration Dates

First Submitted

September 16, 2005

First Submitted That Met QC Criteria

September 16, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Estimate)

November 25, 2009

Last Update Submitted That Met QC Criteria

November 24, 2009

Last Verified

November 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORVACS 002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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