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

12 juni 2013 uppdaterad av: 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

Studieöversikt

Status

Avslutad

Betingelser

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

29

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

      • Paris, Frankrike, 75013
        • Groupe Hospitalier Pitie-Salpetriere
      • Milan, Italien, 20127
        • San Raffaele Scientific Institute
      • Badalona, Spanien, 08916
        • Fundacio Irsicaixa
      • Barcelona, Spanien, 08036
        • University Hospital Clinic of Barcelona
      • London, Storbritannien, NW3 2QG
        • Royal Free Hospital

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 70 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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
Experimentell: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
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
Tidsram: End of study
End of study

Sekundära resultatmått

Resultatmått
Tidsram
Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: From Day 0 to Week 56
From Day 0 to Week 56
Proportion of patients without inducible HIV RNA, DNA and/or p24
Tidsram: End of study
End of study
Changes from baseline in CD4 lymphocyte count
Tidsram: 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
Tidsram: End of study
End of study
Development of a mathematical model exploring the dynamics of the HIV-DNA decay
Tidsram: 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)
Tidsram: From Day 0 to Week 56
From Day 0 to Week 56
Genetic determinants influencing HIV-1-specific immune response and HIV control
Tidsram: End of study
End of study
Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa
Tidsram: From Day 0 to Week 56
From Day 0 to Week 56
Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy
Tidsram: From Day 0 to Week 56
From Day 0 to Week 56

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Huvudutredare: Christine Katlama, MD, Groupe Hospitalier Pitie-Salpetriere
  • Studierektor: François LECARDONNEL, MSc, ORVACS
  • Studiestol: Steven DEEKS, MD, University of California, San Francisco

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 september 2010

Primärt slutförande (Faktisk)

1 juli 2012

Avslutad studie (Faktisk)

1 februari 2013

Studieregistreringsdatum

Först inskickad

23 november 2009

Först inskickad som uppfyllde QC-kriterierna

24 november 2009

Första postat (Uppskatta)

25 november 2009

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

13 juni 2013

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

12 juni 2013

Senast verifierad

1 juni 2013

Mer information

Termer relaterade till denna studie

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Kliniska prövningar på HIV-1-infektion

Kliniska prövningar på ART Intensification

3
Prenumerera