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

This study has been completed.
Sponsor:
Information provided by:
Objectif Recherche Vaccins SIDA
ClinicalTrials.gov Identifier:
NCT00219362
First received: September 16, 2005
Last updated: November 24, 2009
Last verified: November 2009
  Purpose

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.


Condition Intervention Phase
HIV Infection
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
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Objectif Recherche Vaccins SIDA:

Primary Outcome Measures:
  • Change from baseline of the frequency of HIV-specific PBMC (CD4/CD8) at W24 (4 weeks after the last immunization)

Secondary Outcome Measures:
  • - 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

Enrollment: 65
Study Start Date: April 2004
Study Completion Date: September 2006
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00219362

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

Publications:
Responsible Party: Pr Christine KATLAMA, Objectif Recherche Vaccins SIDA
ClinicalTrials.gov Identifier: NCT00219362     History of Changes
Other Study ID Numbers: ORVACS 002
Study First Received: September 16, 2005
Last Updated: November 24, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration
Spain: Spanish Agency of Medicines
Germany: Paul-Ehrlich-Institut

Keywords provided by Objectif Recherche Vaccins SIDA:
HIV-1 infection
therapeutic vaccine
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on April 22, 2014