E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
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) |
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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
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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 |
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
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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 while being seropositive (incl. single dose administration, fx to prevent MTCT). Having received ART while seronegative (PEP or PrEP) is not a non-inclusion criterion as long as an HIV negative test is documented at least 3 months post-PEP or -PrEP.
• HIV-1 RNA > 1000 copies/ml
• Indication to start an antiretroviral treatment 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
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E.4 | Principal exclusion criteria |
• Woman without effective contraception method. For contraception during the trial all women must use a combination of mechanical methods and a second method other than 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 an oral contraceptive and this is not a non-inclusion criterion
• 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 g/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) 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. 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
• 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
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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 by a subsequent measure*)
•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 measure*)
•HIV-1 RNA ≥ 50 copies/ml (confirmed by a subsequent measure*) 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
*In case of treatment modification for virological reasons, it is mandatory to take the retest sample before any treatment modification. |
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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 | 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 | 1 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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Last patient last visit will define the end 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 | 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 |