Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients

NCT ID: NCT01019551

Last Updated: 2013-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-30

Study Completion Date

2013-02-28

Brief Summary

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

Detailed Description

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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.

Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ARM A : ART intensification alone

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

Group Type EXPERIMENTAL

ART Intensification

Intervention Type 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 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

Group Type EXPERIMENTAL

ART Intensification

Intervention Type 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

Immunomodulation

Intervention Type 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.

Interventions

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ART 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

Intervention Type DRUG

Immunomodulation

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cytheris SA

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

Objectif Recherche Vaccins SIDA

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine KATLAMA, MD

Role: PRINCIPAL_INVESTIGATOR

Groupe Hospitalier Pitié-Salpêtrière

Steven DEEKS, MD

Role: STUDY_CHAIR

University of California, San Francisco

François LECARDONNEL, MSc

Role: STUDY_DIRECTOR

ORVACS

Locations

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Groupe Hospitalier Pitié-Salpêtrière

Paris, , France

Site Status

San Raffaele Scientific Institute

Milan, , Italy

Site Status

Fundacio Irsicaixa

Badalona, , Spain

Site Status

University Hospital Clinic of Barcelona

Barcelona, , Spain

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

Countries

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France Italy Spain United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 19498149 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21422987 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 22415474 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21566173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21255462 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26684819 (View on PubMed)

Other Identifiers

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ORVACS 010

Identifier Type: -

Identifier Source: org_study_id

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