E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Patients infected with HIV under antiretroviral treatment which viral load is controlled on a long-term basis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008919 |
E.1.2 | Term | Chronic HIV infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Important decrease in the HIV-1 viral reservoir |
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E.2.2 | Secondary objectives of the trial |
- Eradicate HIV in the lymphoid reservoirs of HIV in the gut - To describe the immunologic effects of treatment intensification with and without immunomodulatory therapy - Develop a model for HIV DNA decay in patients receiving treatment intensification with and without immunomodulatory therapy - Determine the safety of treatment intensification with and without immunomodulatory therapy |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional sub-study : Immunologic and virologic evaluation of the impact of the ERAMUNE-01 study treatments on the HIV-1 reservoir associated to the rectal mucosa". Vercion 1.0 Objectives: important decrease of the proviral HIV DNA in the lymphoid tissue associated to the rectal mucosa |
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E.3 | Principal 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. |
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E.4 | Principal 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 the 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Percentage of patients with undetectable HIV DNA (< 1 copy/106 PBMCs) after 56 weeks • Changes from baseline in CD4 lymphocyte count • Change from baseline in HIV proviral DNA in any of the subcompartments explored (gut lymphoid tissue), as expressed as numbers of HIV DNA copies per million mononuclear cells • Change from baseline in HIV proviral DNA in the CD4 T cell subset, as expressed as numbers of HIV DNA copies per million CD4 T cells • Changes from baseline in HIV plasma viral load (number of copies of HIV RNA per millilitre), measured by quantitative ultrasensitive PCR • Proportion of patients without inducible HIV RNA, DNA and/or p24 • Changes in the activation and differentiation markers of the CD4 and CD8 peripheral blood T cells • Development of a mathematical model exploring the dynamics of the HIV-DNA decay • Development of a mathematical model exploring the dynamics of T cells activation (CD38) • Genetic determinants influencing HIV-1-specific immune response and HIV control • Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa • Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial : Completion of all trial procedures. Last patient last visit A Data and Safety Monitoring Board (DSMB) will be installed to monitor accumulating data in this trial. The role of the DSMB is to review the progress of the trial and the accumulating data to detect evidence of early safety issues for the subjects while the trial is ongoing. The DSMB will give recommendation regarding modification to the ongoing conduct of the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |