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Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients (ERAMUNE-01)

12 juin 2013 mis à jour par: Objectif Recherche Vaccins SIDA

International, Multicenter, Randomized, Non-comparative Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression

Viral eradication in selected HIV-infected patients is possible with intensive antiretroviral therapy plus immunomodulation

Aperçu de l'étude

Statut

Complété

Les conditions

Description détaillée

The overall strategy of the ERAMUNE 01 Trial is to treat selected patients with an optimal synergistic antiretroviral regimen plus one or more immunomodulating agents. Among immunomodulating treatments the candidates include therapies from two functional classes: 1) agents that target actively replicating cells and 2) agents activating latently infected cells31.

The novelty of this approach is three-fold: first, the use of highly potent antiretroviral therapy combining drugs with different HIV enzymes targets or receptors and different penetrations in cells, with the aim to suppress virus to truly undetectable levels as measured by the most sophisticated viral quantification techniques; secondly, the addition of an immunomodulatory therapy that specifically targets viral reservoirs to this intensification strategy; and lastly, the rigorous selection of patients having already a low HIV reservoir as measured by peripheral blood HIV DNA content. To our knowledge, this type of strategy has not been implemented. We believe this strategy is feasible.

Type d'étude

Interventionnel

Inscription (Réel)

29

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Badalona, Espagne, 08916
        • Fundacio Irsicaixa
      • Barcelona, Espagne, 08036
        • University Hospital Clinic of Barcelona
      • Paris, France, 75013
        • Groupe Hospitalier Pitie-Salpetriere
      • Milan, Italie, 20127
        • San Raffaele Scientific Institute
      • London, Royaume-Uni, NW3 2QG
        • Royal Free Hospital

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • HIV-1 infection, documented by any licensed ELISA test kit and confirmed by Western Blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test
  • 18 ≤ Age ≤ 70 years
  • At least 3 years of suppressive ART without any interruption (less than one month cumulative),
  • ART treatment unchanged in the 3 months prior to screening
  • One HIV plasma viral load (RNA) documented at least 3 years prior to entry, and at least 2 HIV plasma viral loads (RNA) documented per year thereafter
  • HIV plasma viral load (RNA) ≤ 500 copies/ml at least 3 years prior to entry and HIV plasma viral load ≤ 500 copies/ml for ≥ 90% of the measures thereafter
  • HIV plasma viral load (RNA) below the limit of detection for all values within the past year. Note: the assay used must have a lower limit of detection of 75 copies/ml or less
  • CD4+ count ≥ 350 cells/mm3 within 60 days of entry
  • 10 ≤ Proviral DNA ≤ 1000 copies/106 PBMCs within 60 days of entry
  • Documented laboratory values: Haemoglobin ≥ 10 g/dl, Platelets ≥ 100,000 per microliter, Hepatic transaminases ≤ 2.5 x ULN, Creatinine clearance ≥ 50 ml/min by the Cockcroft-Gault equation
  • All subjects must agree not to participate in the conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable forms of contraceptives (condoms, with or without spermicidal agent, a diaphragm or cervical cap with spermicide, an IUD, or hormone-based contraception), while receiving study treatment and for 6 weeks after stopping study treatment
  • Ability and willingness to provide informed consent.

Exclusion Criteria:

  • Sexually active men and women who will not practice at least one form of barrier birth control (male partner using condoms, female partner using condoms, other barrier contraception, etc)
  • Pregnancy as documented by a urine pregnancy test, or lactating women
  • Hepatitis B antigen (HBsAg) positive
  • Hepatitis C virus (HCV-Ab) positive or HCV RNA detectable
  • Previous use of an integrase inhibitor (ie raltegravir) or a CCR5 inhibitor (ie maraviroc, vicriviroc). Use of raltegravir for non-treatment failure indications such as intensification and toxicity switches is allowed, provided that 1) virologic suppression was maintained before, during and after raltegravir treatment and 2) the patient has not received raltegravir treatment in the 6 months prior to study entry.
  • Previous immunologic therapeutic intervention (e.g. IL-2, IL-7) within the past year
  • Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted
  • Diagnosis of cancer within the last 5 years (except basal cell cutaneous cancers and cutaneous KS not requiring systemic therapy)
  • Co-morbid condition with an expected survival less than 12 months
  • History of hypersensitivity to vaccination
  • History of autoimmune disease, such as systemic lupus erythematosis (SLE) or Hashimoto's thyroiditis
  • Active drug or alcohol use or dependence that, in the opinion of the center investigator, would interfere with adherence to study requirements.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: ARM A : ART intensification alone
Raltegravir PO 400 mg BID Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen
Current ART regimen plus raltegravir and maraviroc Raltegravir : 400 mg PO BID for 56 weeks Maraviroc : 150, 300 or 600 mg PO BID depending on concomitant ART treatment, for 56 weeks
Expérimental: ARM B : ART intensification + Immunomodulation
Raltegravir PO 400 mg BID during 56 weeks Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen during 56 weeks 3 weekly injections of r-hIL-7 (CYT107) at a 20 micrograms/kg dose starting at Week 8
Current ART regimen plus raltegravir and maraviroc Raltegravir : 400 mg PO BID for 56 weeks Maraviroc : 150, 300 or 600 mg PO BID depending on concomitant ART treatment, for 56 weeks
Starting at Week 8, 1 cycle of 3 injections (1 per week) of recombinant human Interleukin-7 (r-hIL-7 / CYT107) at a 20 µg/kg dose.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Decrease from baseline in HIV proviral DNA in the PBMCs at week 56 of at least 0.5 log, as expressed as numbers of HIV DNA copies per million PBMCs
Délai: End of study
End of study

Mesures de résultats secondaires

Mesure des résultats
Délai
Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks
Délai: End of study
End of study
Change from baseline in HIV proviral DNA in any of the sub-compartments explored (gut lymphoid tissue), as expressed as numbers of HIV DNA copies per million mononuclear cells
Délai: From Day 0 to Week 56
From Day 0 to Week 56
Change from baseline in HIV proviral DNA in the CD4 T cell subsets, as expressed as numbers of HIV DNA copies per million CD4 T cells
Délai: From Day 0 to Week 56
From Day 0 to Week 56
Changes from baseline in HIV plasma viral load (number of copies of HIV RNA per millilitre), measured by quantitative ultrasensitive PCR
Délai: From Day 0 to Week 56
From Day 0 to Week 56
Proportion of patients without inducible HIV RNA, DNA and/or p24
Délai: End of study
End of study
Changes from baseline in CD4 lymphocyte count
Délai: From Day 0 to Week 56
From Day 0 to Week 56
Changes in the activation and differentiation markers of the CD4 and CD8 peripheral blood T cells
Délai: End of study
End of study
Development of a mathematical model exploring the dynamics of the HIV-DNA decay
Délai: From Day 0 to Week 56
From Day 0 to Week 56
Development of a mathematical model exploring the dynamics of T cells activation (CD38)
Délai: From Day 0 to Week 56
From Day 0 to Week 56
Genetic determinants influencing HIV-1-specific immune response and HIV control
Délai: End of study
End of study
Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa
Délai: From Day 0 to Week 56
From Day 0 to Week 56
Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy
Délai: From Day 0 to Week 56
From Day 0 to Week 56

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chercheur principal: Christine Katlama, MD, Groupe Hospitalier Pitie-Salpetriere
  • Directeur d'études: François LECARDONNEL, MSc, ORVACS
  • Chaise d'étude: Steven DEEKS, MD, University of California, San Francisco

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 septembre 2010

Achèvement primaire (Réel)

1 juillet 2012

Achèvement de l'étude (Réel)

1 février 2013

Dates d'inscription aux études

Première soumission

23 novembre 2009

Première soumission répondant aux critères de contrôle qualité

24 novembre 2009

Première publication (Estimation)

25 novembre 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

13 juin 2013

Dernière mise à jour soumise répondant aux critères de contrôle qualité

12 juin 2013

Dernière vérification

1 juin 2013

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • ORVACS 010

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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