| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV-1 infection |
| Infection au VIH-1 |
|
| E.1.1.1 | Medical condition in easily understood language |
| HIV-1 infection |
| Infection au VIH-1 |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| 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 evaluate the non-inferiority of switching to a DTG containing regimen relative to maintaining a boosted PI containing regimen in virologically-suppressed HIV-1 positive subjects as determined by having HIV-1 RNA < 50 c/ml at Week 48
• To determine the effect of a DTG containing regimen relative to maintaining a boosted PI containing regimen as determined by change in total cholesterol after 48 weeks
|
• Évaluer la non-infériorité du passage à un schéma thérapeutique contenant du DTG comparé au maintien d’un schéma thérapeutique contenant des IP renforcés, chez des sujets positifs au VIH-1, déterminée par la présence de < 50 c/ml de l’ARN du VIH-1 à la semaine 48
• Déterminer l’innocuité d’un schéma thérapeutique contenant du DTG comparé au maintien d’un schéma thérapeutique contenant des IP renforcés, établie par une variation du cholestérol total au bout de 48 semaines
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| E.2.2 | Secondary objectives of the trial |
• To assess the impact of switching to DTG on maintenance of virological suppression at Weeks 24 and 96
• To assess the impact of switching on CD4 count
• To assess the impact of switching to DTG on cardiovascular risk as determined by change in total cholesterol after 24 and 96 weeks
• To assess the impact of switching to DTG on cardiovascular risk after 48 and 96 weeks as determined by
o lipid values
o Framingham scores
o DAD scores
• To investigate the impact of switching to DTG on safety and tolerability
• To investigate the potential for improvements in markers of inflammation, coagulation and endothelial dysfunction in stored plasma, serum and urine samples
• To investigate the impact on quality of life (as determined by EuroQoL questionnaire)
|
• Déterminer l’effet du passage au DTG sur le maintien de la suppression virale aux semaines 24 et 96
• Déterminer l’effet de ce passage sur la numération des CD4
• Évaluer l’effet du passage au DTG sur le risque cardiovasculaire, établi par une variation dans le cholestérol total au bout de 24 et 96 semaines
• Évaluer l’effet du passage au DTG sur le risque cardiovasculaire au bout de 48 et 96 semaines, établi par
o les valeurs des lipides
o les scores de Framingham
o les scores DAD (évaluation de la démence sévère)
• Étudier l’effet du passage au DTG sur l’innocuité et la tolérabilité
• Étudier la possibilité d’une amélioration dans les marqueurs de l’inflammation, de la coagulation et de la dysfonction endothéliale dans des échantillons de sang et d’urine archivés
• Étudier l’effet sur la qualité de vie (déterminé par le questionnaire EuroQoL)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| HIV-infected individuals on PI/r plus 2 NRTIs, with a viral load <50 copies/mL for >24 weeks, aged >50 years OR >18 years with a Framingham CVS risk score above 10% |
| Sujets infectés par le VIH traités aux IP/r plus deux INTI, présentant une charge virale < 50 copies/ml pendant > 24 semaines, âgés de 50 ans et plus OU de 18 ans et plus, et dont le score de risque cardiovasculaire de Framingham est supérieur à 10 %. |
|
| E.4 | Principal exclusion criteria |
1. Infected with HIV-2
2. Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs
3. Has acute viral hepatitis including, but not limited to, A, B, or C
4. Has chronic hepatitis B and/or C with AST and/or ALT >5 x ULN
Note: Subjects can enter trial with chronic HBV if HBV-DNA undetectable at screen (and no detectable result in last 6 months) and with chronic HCV if not expected to require treatment during the trial period.
5. Any investigational drug within 30 days prior to the trial drug administration
6. History of exposure to any ARVs other than PIs or NRTIs except if switch was for tolerability/toxicity (NOTE: patients who have previously taken part in single drug trials for less than 14 days need not be excluded, or for virological failure with a genotypic resistance test without mutations
7. Any prior evidence of primary viral resistance based on the presence of any major resistance-associated mutation to backbone NRTI
8. History of prior virological failure,eg 2 consecutive HIV-1 RNA >50 c/ml -at or after week 32 following first ART initiation or confirmed rebound viraemia >200 copies/ml after having a VL of <50 copies/ml without resistance test or with significant mutations to any other ARV regimen (NOTE: Switch for toxicity or tolerability with wild type virus does not count as virological failure)
9. Dialysis or renal insufficiency (creatinine clearance < 50ml/min)
10. History of decompensated liver disease (AST or ALT≥5x the upper limit of normal (ULN) or ALT ≥ )3 x ULN and bilirubin ≥ 1.5 x ULN with > 35% direct bilirubin.
11. Unstable liver disease (as defined by the presence of ascities, encephalopathy, coagulopathy, hypoalbuminemia, esophagael or gastic varices, or persistent jaundice), know biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones))
12. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification (see appendix 5)
13. If female, currently pregnant or breastfeeding
14. Opportunistic infection within 4 weeks prior to first dose of DTG
15. Clinical decision that a switch of antiretroviral therapy should be immediate
16. Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).
17. Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the trial.
18. History or presence of allergy to the study drug or their components |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
• Maintenance of virological suppression (ie HIV-1 RNA <50 c/ml) after 48 weeks
• Change from baseline in total cholesterol at week 48
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• Maintien de la suppression virale (c’est-à-dire ARN du VIH-1 <50 c/ml) au bout de 48 semaines
• Variation du cholestérol total par rapport à l’évaluation initiale à la semaine 48
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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) |
• Maintenance of virological suppression (ie HIV-1 RNA <50 c/ml) at week 24 and 96
• Change in CD4 count from baseline to week 24, 48 and 96
• Change from baseline in total cholesterol at weeks 24 and 96
• Change from baseline to lipid values (LDL, HDL, triglycerides and TC:HDL ratio) and Framingham and DAD scores at weeks 24, 48 and 96
• Safety (clinical and laboratory adverse events) at weeks 24, 48 and 96
• Changes in markers of inflammation, coagulation and endothelial dysfunction at baseline, week 48 and week 96
• Tolerability (EuroQoL questionnaire) at weeks 24, 48 and 96
|
• Maintien de la suppression virale (c’est-à-dire ARN du VIH-1 <50 c/ml) aux semaines 24 et 96
• Variation dans la numération des CD4 totales depuis l’évaluation initiale jusqu’aux semaines 24, 48 et 96
• Variation du cholestérol total par rapport à l’évaluation initiale aux semaines 24 et 96
• Variations des valeurs lipidiques (LDL, HDL, triglycérides et ratio CT/HDL) et scores de Framingham et DAD aux semaines 24, 48 et 96
• Innocuité (événements indésirables observés cliniquement et en laboratoire) aux semaines 24, 48 et 96
• Variations dans les marqueurs de l’inflammation, de la coagulation et de la dysfonction endothéliale à l’évaluation initiale, à la semaine 48 et à la semaine 96
• Tolérabilité (questionnaire EuroQoL) aux semaines 24, 48 et 96 |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 24, 48 and 96 weeks |
| 24, 48 et 96 semaines |
|
| 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 | No |
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | No |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| 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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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 3 |
| 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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