Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients

NCT01019551 | Completed Phase 2 DMC

• 1 other identifier: ORVACS 010
• Study Type: interventional
• Target: 29
• Locations: 4 countries
• Sites: 5

Brief Summary

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

Conditions

HIV-1 Infection

Keywords

Controlled viremia; Viral reservoirs; Virus eradication; Therapeutic intensification; Immunointervention

Outcome Measures

Primary Outcomes (1)

• 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

  End of study

Secondary Outcomes (12)

• Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks

  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

  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

  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

  From Day 0 to Week 56

• Proportion of patients without inducible HIV RNA, DNA and/or p24

  End of study

Study Arms (2)

ARM A : ART intensification alone

EXPERIMENTAL

Raltegravir PO 400 mg BID Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen

Drug: ART Intensification

ARM B : ART intensification + Immunomodulation

EXPERIMENTAL

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

Drug: ART Intensification; Biological: Immunomodulation

Interventions

ART Intensification DRUG

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

ARM A : ART intensification alone; ARM B : ART intensification + Immunomodulation

Immunomodulation BIOLOGICAL

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.

ARM B : ART intensification + Immunomodulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ≤ 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
• ≤ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Objectif Recherche Vaccins SIDA: lead
• Cytheris SA: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Pfizer: collaborator

Study Sites (5)

Groupe Hospitalier Pitié-Salpêtrière

Paris, 75013, France

Location

San Raffaele Scientific Institute

Milan, 20127, Italy

Location

Fundacio Irsicaixa

Badalona, 08916, Spain

Location

University Hospital Clinic of Barcelona

Barcelona, 08036, Spain

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (6)

• Murphy RL, Autran B, Katlama C, Brucker G, Debre P, Calvez V, Clotet B, Clumeck N, Costagliola D, Deeks SG, Dorrell L, Gatell J, Haase A, Klein M, Lazzarin A, McMichael AJ, Papagno L, Schacker TW, Wain-Hobson S, Walker BD, Youle M. A step ahead on the HIV collaboratory. Science. 2009 Jun 5;324(5932):1264-5. doi: 10.1126/science.324_1264b. No abstract available.

  PMID: 19498149 BACKGROUND

• Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the laboratory to effective clinical trials? AIDS. 2011 Apr 24;25(7):885-97. doi: 10.1097/QAD.0b013e3283467041.

  PMID: 21422987 BACKGROUND

• Lafeuillade A. Eliminating the HIV reservoir. Curr HIV/AIDS Rep. 2012 Jun;9(2):121-31. doi: 10.1007/s11904-012-0115-y.

  PMID: 22415474 BACKGROUND

• Cohen J. The emerging race to cure HIV infections. Science. 2011 May 13;332(6031):784-5, 787-9. doi: 10.1126/science.332.6031.784. No abstract available.

  PMID: 21566173 BACKGROUND

• Lewin SR, Evans VA, Elliott JH, Spire B, Chomont N. Finding a cure for HIV: will it ever be achievable? J Int AIDS Soc. 2011 Jan 24;14:4. doi: 10.1186/1758-2652-14-4.

  PMID: 21255462 BACKGROUND

• Katlama C, Lambert-Niclot S, Assoumou L, Papagno L, Lecardonnel F, Zoorob R, Tambussi G, Clotet B, Youle M, Achenbach CJ, Murphy RL, Calvez V, Costagliola D, Autran B; EraMune-01 study team. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS. 2016 Jan;30(2):221-30. doi: 10.1097/QAD.0000000000000894.

  PMID: 26684819 DERIVED

MeSH Terms

Interventions

Immunomodulation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Immune System Phenomena

Study Officials

• Christine KATLAMA, MD

  Groupe Hospitalier Pitié-Salpêtrière

  PRINCIPAL INVESTIGATOR

• Steven DEEKS, MD

  University of California, San Francisco

  STUDY CHAIR

• François LECARDONNEL, MSc

  ORVACS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2009
• First Posted: November 25, 2009
• Study Start: September 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: February 1, 2013
• Last Updated: June 13, 2013

Record last verified: 2013-06

Locations

IT (1); GB (1); FR (1); ES (2)