Official Title: “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

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2011

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.

Intervention(s) in this Clinical Trial

• Drug: HAART Intensification
  • 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
• Biological: Immunomodulation
  • 2 cycles of 3 injections (1 per week) of recombinant human Interleukin-7 (r-hIL-7 / CYT107) at a 20 µg/kg dose. First cycle at Week 8, second cycle at Week 28

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: ARM A
  • Therapeutic Intensification alone
• Experimental: ARM B
  • Therapeutic Intensification plus Immunomodulation

Primary Measures

• 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
  • Time Frame: End of study
    Safety Issue?: No

Secondary Measures

• Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks
  • Time Frame: End of study
    Safety Issue?: No
• 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
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: No
• 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
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: No
• Changes from baseline in HIV plasma viral load (number of copies of HIV RNA per millilitre), measured by quantitative ultrasensitive PCR
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: No
• Proportion of patients without inducible HIV RNA, DNA and/or p24
  • Time Frame: End of study
    Safety Issue?: No
• Changes from baseline in CD4 lymphocyte count
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: No
• Changes in the activation and differentiation markers of the CD4 and CD8 peripheral blood T cells
  • Time Frame: End of study
    Safety Issue?: No
• Development of a mathematical model exploring the dynamics of the HIV-DNA decay
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: No
• Development of a mathematical model exploring the dynamics of T cells activation (CD38)
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: No
• Genetic determinants influencing HIV-1-specific immune response and HIV control
  • Time Frame: End of study
    Safety Issue?: No
• Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: No
• Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy
  • Time Frame: From Day 0 to Week 56
    Safety Issue?: Yes

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 ≤ 60 years
• At least 3 years of ART (defined as at least 3 ART medications) without any interruption for more 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 ≤ 500 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)
• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Objectif Recherche Vaccins SIDA

Overall Clinical Trial Officials and Contacts

Christine KATLAMA, MD Principal Investigator Groupe Hospitalier Pitié-Salpêtrière  

Overall Contact: Christine KATLAMA, MD +33142160130 christine.katlama@psl.aphp.fr

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01019551

Study ID Number: ORVACS 010

ClinicalTrials.gov Identifier: NCT01019551

Health Authority: France: Afssaps - French Health Products Safety Agency