| 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 | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020161 |
| E.1.2 | Term | HIV infection |
|
| 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 1.5 times the risk with darunavir/r + tenofovir/emtricitabine) |
|
| E.2.2 | Secondary objectives of the trial |
Comparison of 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 |
A) Viral and immunologic dynamics and inflammation sub-study:
To study the correlation between viral decay and immunologic parameters;
To compare between the two treatment strategies:
• the early immunologic dynamics in relationship with the viral dynamics
• the efficacy to reduce the immune activation over 96 weeks as assessed by the numbers of CD38 molecules expressed by CD8 T cells and their co-expression with HLA-DR on CD8 T cells ; reduce the CD4 cell expression of CCR5, the main HIV co-receptor of entry, the expression of which is associated to immune activation as assessed by the quantification of CCR5 molecules on CD4 T cells and their co-expression with HLA-DR ; reduce plasma levels of seric markers of immune activation linked to inflammation and cardiovascular alterations (among those: IL-6, V-CAM…) ; induce immune restoration of naïve and memory T cells numbers and functional competence against pathogens and HIV
• lipid changes
• glucose metabolism changes
• endothelial damage
• change in cardiovascular risk
• change in proinflammatory cytokines
• change in coagulation parameters
To identify the best surrogate of viral suppression in the two treatment arms;
To study the association between residual viral replication, proviral DNA, immune activation, endothelial activation, and inflammation.
B) Bone sub-study
• To compare changes in bone mineral density between the two treatments strategies
• To compare markers of bone metabolism between groups
• To determine the relationships between changes in BMD and changes in body composition
C) Neurocognitive function sub-study
• To compare the efficacy of the two NEAT 001/ANRS 143 treatment strategies on psychomotor speed
• To compare the impact of the two NEAT 001/ANRS 143 treatment strategies on other cognitive, professional and functional activity measures
• To investigate the association between viral load, immune activation and neurocognitive function |
|
| E.3 | Principal inclusion criteria |
• Patient with confirmed HIV infection
• Age ≥ 18 years • Written informed consent
• Male patient or non-pregnant, non-lactating female
• No previous treatment with any antiretroviral drugs
• HIV-1 RNA > 1000 copies/ml • Indication to start an antiretroviral treatment as long as subject has also a CD4 cell count ≤ 500/mm3
• 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 without effective contraception method (recommended contraception during the trial is mechanical + spermicides. Oral contraceptives are not to be used during the trial)
• Pregnant or breastfeeding woman
• Woman expecting to conceive during the study
• HIV-2 co-infection
• Creatinine clearance < 60 ml/mn (Cockcroft & Gault equation), alkaline phosphatase, ASAT, or ALAT ≥ 5 ULN
• Patient with significant impairment of hepatic function, defined as serum albumin < 2.8 mg/dl or INR > 1.7 or presence of ascites, in the absence of another explanation for the abnormal finding
• CD4 > 500/mm3, except in case of symptomatic HIV disease (defined by conditions qualifiying for CDC category B or C)
• Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or protease inhibitors on genotypic testing at screening
• 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
• Known hypersensitivity to one of the trial drugs or its 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) |
Time to virologic or clinical failure, as the first occurrence of any of the following components:
• failure to achieve virologic response by W32 (defined as HIV-1 RNA ≥ 50 copies/ml at W32, confirmed within 4 weeks)
• 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 within 4 weeks)
• HIV-1 RNA ≥ 50 copies/ml (confirmed within 4 weeks) at any time after W32
• death due to any cause
• any new or recurrent AIDS defining event confirmed by the Endpoint Review Committee
• any new serious non AIDS defining event confirmed by the Endpoint Review Committee |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | 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 | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 97 |
| 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 | Information not present in EudraCT |
| 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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