Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01019551
Other study ID # ORVACS 010
Secondary ID
Status Completed
Phase Phase 2
First received November 23, 2009
Last updated June 12, 2013
Start date September 2010
Est. completion date February 2013

Study information

Verified date June 2013
Source Objectif Recherche Vaccins SIDA
Contact n/a
Is FDA regulated No
Health authority France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: The Italian Medicines AgencySpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
Study type Interventional

Clinical Trial Summary

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


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 29
Est. completion date February 2013
Est. primary completion date July 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 70 Years
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
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
Biological:
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.

Locations

Country Name City State
France Groupe Hospitalier Pitié-Salpêtrière Paris
Italy San Raffaele Scientific Institute Milan
Spain Fundacio Irsicaixa Badalona
Spain University Hospital Clinic of Barcelona Barcelona
United Kingdom Royal Free Hospital London

Sponsors (4)

Lead Sponsor Collaborator
Objectif Recherche Vaccins SIDA Cytheris SA, Merck Sharp & Dohme Corp., Pfizer

Countries where clinical trial is conducted

France,  Italy,  Spain,  United Kingdom, 

References & Publications (5)

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. — View Citation

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

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. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 No
Secondary Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks End of study No
Secondary 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 No
Secondary 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 No
Secondary 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 No
Secondary Proportion of patients without inducible HIV RNA, DNA and/or p24 End of study No
Secondary Changes from baseline in CD4 lymphocyte count From Day 0 to Week 56 No
Secondary Changes in the activation and differentiation markers of the CD4 and CD8 peripheral blood T cells End of study No
Secondary Development of a mathematical model exploring the dynamics of the HIV-DNA decay From Day 0 to Week 56 No
Secondary Development of a mathematical model exploring the dynamics of T cells activation (CD38) From Day 0 to Week 56 No
Secondary Genetic determinants influencing HIV-1-specific immune response and HIV control End of study No
Secondary Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa From Day 0 to Week 56 No
Secondary Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy From Day 0 to Week 56 Yes
See also
  Status Clinical Trial Phase
Completed NCT03188523 - Activity of MK-8504 in Anti-retroviral-naïve, Human Immunodeficiency Virus 1 (HIV-1) Infected Participants (MK-8504-002) Phase 1
Active, not recruiting NCT06185452 - Implementation of Out-of-HOspital Administration of the Long-Acting Cabotegravir+Rilpivirine Phase 4
Recruiting NCT02881320 - Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination in Adolescents and Children With Human Immunodeficiency Virus-1 Phase 2/Phase 3
Completed NCT02513771 - Sitagliptin for Reducing Inflammation and Immune Activation Phase 2
Completed NCT02542852 - A Study of a Nucleoside Sparing Regimen in HIV-1 Infected Patients With Detectable Viremia Phase 2
Completed NCT02057796 - Systematic Empirical vs. Test-guided Anti-TB Treatment Impact in Severely Immunosuppressed HIV-infected Adults Initiating ART With CD4 Cell Counts <100/mm3 Phase 4
Terminated NCT02732457 - Allogeneic Hematopoietic Stem Cell Transplantation in HIV-1 Infected Patients
Completed NCT01989910 - Compare the Efficacy and Safety of Raltegravir Versus Efavirenz Combination Therapy in Treatment-naïve HIV-1 Patients Phase 4
Completed NCT01627678 - Immunotherapy With Vacc-C5 With Adjuvant GM-CSF or Alhydrogel in HIV-1-infected Subjects on ART Phase 1/Phase 2
Completed NCT01704781 - Vacc-4x + Lenalidomide vs. Vacc-4x +Placebo in HIV-1-infected Subjects on Antiretroviral Therapy (ART) Phase 1/Phase 2
Completed NCT01403051 - High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART Phase 2
Completed NCT01348308 - Immuno-stimulation With Maraviroc Combined to Antiretroviral Therapy in Advanced Late Diagnosed HIV-1 Infected Patients Phase 3
Completed NCT01466595 - Rifaximin as a Modulator of Microbial Translocation and Immune Activation Phase 2
Completed NCT01511809 - Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression Phase 3
Terminated NCT01130376 - Novel Interventions in HIV-1 Infection Phase 1
Completed NCT00323687 - SONETT: Switch Study to Once Daily HIV Treatment Regimen With Truvada Phase 4
Completed NCT04003103 - Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016) Phase 2
Completed NCT02527096 - A Trial Evaluating Maintenance Therapy With Lamivudine (Epivir®) and Dolutegravir (Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple Highly Active Antiretroviral Therapy (HAART) (ANRS 167 Lamidol) Phase 2
Active, not recruiting NCT04776252 - Open-label, Follow-up of Doravirine/Islatravir (DOR/ISL 100 mg/0.75mg) for Participants With Human Immunodeficiency Virus-1 (HIV-1) Infection (MK-8591A-033) Phase 3
Completed NCT02174159 - Evaluation of Safety, Tolerability, Pharmacokinetics, and Antiretroviral Activity of Ulonivirine (MK-8507) in Human Immunodeficiency Virus (HIV-1)-Infected Participants (MK-8507-003) Phase 1