| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | 10020160 |
| E.1.2 | Term | HIV disease |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 |
| To assess the non-inferiority of darunavir/r + raltegravir compared to darunavir/r + tenofovir/emtricitabine as first-line treatment strategies in HIV-1 infected, antiretroviral naïve adults over at least 96 weeks (i.e. to assess if the risk of clinical or virological failure with darunavir/r + raltegravir is at most 1.53 times the risk with darunavir/r + tenofovir/emtricitabine). |
|
| E.2.2 | Secondary objectives of the trial |
| To compare the two different regimens in terms of: - virologic response - occurrence of disease progression - occurrence of severe non AIDS defining events - occurrence of death - change in CD4 cell count - occurrence of immune reconstitution syndrome - genotypic resistance at virologic failure - clinical and biological tolerance - adherence - quality of life |
|
| 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 |
| Viral and immunologic dynamics and inflammation sub-study. 03 February 2011; version 4.1. Neurocognitive Function Sub-study. 19 November 2009; version 2.0. Bone sub-study. 22 June 2010; version 3.0 See appendices 15, and 17 of the protocol for the objectives of the studies. |
|
| E.3 | Principal inclusion criteria |
| • Patient with confirmed HIV-1 infection (confirmation of HIV antibody positive prior to screening) • Age ≥ 18 years • Written informed consent • Male patient or non-pregnant, non-lactating female patient Women of childbearing age must have a negative serum pregnancy test at screening. All female participants of child bearing potential must use contraception for the month preceding study entry and for the entire duration of the study. Recommended contraception during the trial is mechanical + a second method other than oral contraception. • No previous treatment with any antiretroviral drugs while being seropositive (including single dose administration). Having received ARV while seronegative (post- exposure prophylaxis (PEP) or pre-exposure prophylaxis (Prep) is not a non-inclusion criterion as long as a HIV negative test at least 3 months post-PEP or Prep is documented. (Patients having participated in HIV vaccine studies before inclusion may be included in the trial). • HIV-1 RNA > 1000 copies/ml • Indication to initiate ARV therapy according to current guidelines, as long as subject has also a CD4 cell count ≤ 500 /mm3 either at screening or on a sample taken within 3 months before screening • No major IAS-USA mutations on genotypic testing at the screening visit or on any historical genotype, if available |
|
| E.4 | Principal exclusion criteria |
| • Woman of child-bearing potential without effective contraception method For contraception during the trial all women must use a combination of mechanical methods and a second method other than an oral contraceptive. Oral contraceptives are not to be used during the trial unless there is a medical indication. In these circumstances women must also use a mechanical method plus a second method other than oral contraceptive and this is not a non-inclusion criterion. • Pregnant or breastfeeding woman • Woman expecting to conceive during the study period • HIV-2 co-infection • Creatinine clearance < 60 ml/mn (estimated glomerular filtration rate according to the Cockcroft & Gault equation), alkaline phosphatase, ASAT or ALAT ≥ 5 times the upper limit of the norm (ULN) • Patient with significant impairment of hepatic function, defined as serum albumin < 2.8 g/dl or INR > 1.7 or presence of ascites, in the absence of another explanation for the abnormal finding • CD4 > 500/mm3 at screening, except in case of symptomatic HIV disease (defined by conditions qualifying for CDC category B or C or CD4 ≤ 500 /mm3 on a sample taken within 3 months before screening • Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or protease inhibitors on genotypic testing at screening or on any historical genotype if available (December 2009 list, see http://www.iasusa.org/resistance_mutations). Any previous genotype result is valid, with no time limit, as long as the original test result is documented • Mycobacteriosis under treatment • Malignancy requiring chemotherapy or radiotherapy • Positive HBs Ag • HCV infection for which specific treatment is ongoing or planned during the first year on trial treatment. Protocol-specified concomitant hepatitis C treatment is allowed after the first 12 months on trial treatment. • Known hypersensitivity to one of the trial drugs, the metabolites or formulation excipients • Contraindicated concomitant treatment • Anticipated non-compliance with the protocol • Participation in another clinical trial with an on-going exclusion period at screening • Subject under legal guardianship or incapacitation • Subject, who in the opinion of the investigator, is unable to complete the study period |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of the study is time to virologic or clinical failure, defined as the first occurrence of any of the following six components: 1: failure to achieve virologic response by W32 (defined as HIV-1 RNA ≥ 50 copies/ml at W32, confirmed by a subsequent measurement*) 2: change of any component of the initial randomised regimen before W32 because of documented insufficient virologic response, defined as HIV-1 RNA reduction < 1 log10 copies/ml by W18 or HIV-1 RNA ≥ 400 copies/ml at W24 (confirmed by a subsequent measurement*). 3: HIV-1 RNA ≥ 50 copies/ml (confirmed by a subsequent measurement*) at any time after W32 4: death due to any cause 5: any new or recurrent AIDS defining event (category C events as defined in appendix 4 of the protocol) confirmed by the Endpoint Review Committee 6: any new serious non AIDS defining event, as defined in appendix 5 of the protocol, confirmed by the Endpoint Review Committee. *In case of treatment modification for virological reasons, it is mandatory to take the retest sample before any treatment modification. |
|
| 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 | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 96 |
| 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
|
| Last patient last visit will define the end of the trial |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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