| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV-1 infection |
| Infección por VIH-1 |
|
| E.1.1.1 | Medical condition in easily understood language |
| HIV-1 infection |
| Infección por 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 |
? Evaluar la no inferioridad en la determinación ARN de VIH-1 < 50 copias/ml a las 48 semanas del cambio a un régimen que contenga DTG respecto al mantenimiento de un régimen que contenga un IP potenciado en sujetos VIH-1 seropositivos virológicamente suprimidos
? Determinar el efecto sobre el cambio en el colesterol total de un régimen que contenga DTG respecto al mantenimiento de un régimen que contenga un IP potenciado a las 48 semanas |
|
| 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) |
? Evaluar el impacto del cambio a DTG sobre el mantenimiento de la supresión virológica a las 24 y 96 semanas
? Evaluar el impacto del cambio sobre el recuento de CD4
? Evaluar el impacto del cambio a DTG sobre el riesgo cardiovascular en función del cambio en el colesterol total a las 24 y 96 semanas
? Evaluar el impacto del cambio a DTG sobre el riesgo cardiovascular a las 48 y 96 semanas en función de:
o valores de los lípidos
o Registros Framingham
o Registros DAD
? Investigar el impacto del cambio a DTG sobre la seguridad y la tolerancia
? Investigar el potencial de mejoras en los marcadores de inflamación, coagulación y disfunción endotelial en muestras de sangre y orina almacenadas
? Investigar el impacto sobre la calidad de vida (en base al cuestionario 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% |
| Individuos infectados por VIH en tratamiento con IP/r más 2 NRTI, con una carga viral <50 copias/ml durante >24 semanas, ? 50 años O ? 18 años con un resultado de riesgo cardiovascular Framingham superior al 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 |
1. Infectados por el VIH-2
2. En tratamiento con cualquier medicaión concomitante prohibida según datos de seguridad incluidos en las fichas técnicas de los productos en investigación
3. Infección aguda por el virus de la Hepatitis incluida, pero no limitada a, A, B o C
4. Infección crónica por el virus de la Hepatitis B y/o C con valores de GOT y/o GPT > 5 x LSN
Nota: pueden entrar en el estudio pacientes con infección crónica VHB siempre y cuando el valor de DNA-VHB sea indetectable en el screening (y no se tengan valores detectables durante los últimos 6 meses) y pacientes con infección crónica VHC si no requieren de tratamiento durante la duración del estudio.
5. Cualquier medicamento en investigación dentro de los 30 días previos al inicio del estudio
6. Historia previa de exposición a otros antirretrovirales distintos de IPs o ITIN excepto si el cambio fue por causas de tolerabilidad /toxicidad
7. CUalquier evidencia previa de resistencia primaria basada en la presencia de cualquier resistencia mayor asociada a mutación a los componentes NRTI
8. Historia previa de fracaso virológico,ej 2 determinaciones consecutivas de HIV-1 RNA >50 copias/ml -durante o después de la semana 32 en tratamiento consu primer ART o confirmación de rebote virológico de >200 copias/ml después dde una carga viral de <50 copias/ml sin test de resistencia o con mutaciones significativas a otros regimenes ARV
9. Dialisis o insuficiencia renal (aclaramiento de creatinina < 50ml/min)
10. Historia de descompensación hepática (GOT o GPT?5x LSN or GPT ? 3 x LSN y bilirrubina ? 1.5 x LSN con > 35% bilirrubina directa
11. Enfermedad hepática inestable (definida como presencia de ascitis, encefalopatía, coagulopatía, hipoalbuminumia, varices esofágicas o gástricas, o ictericia persistente), s defined by the presence of ascities, encephalopathy, coagulopathy, hypoalbuminemia, esophagael or gastic varices, or persistent jaundice),alteraciones biliares conocidas (con la excepción del síndrome de Gilbert o cálculos biliares asintomáticos.)
12. Sujetos con insuficiencia hepática grave (clase C) según clasificación de Child-Pugh (ver apéndice 5)
13. En el caso de mujeres, embarazo o lactancia
14. Infección oportunista dentro de las 4 semanas previas a la primera dosis de DTG
15. Decisión clínica sobre la necesidad de interrumpir el tratamiento antirretroviral de manera inmediata
16. Cualquier alteración de laboratorio de grado 3/4 durante el screening según clasificación de toxicidad de la División de SIDA, excepto: glucosa asintomática de grado 3, amilasa o elevación de lípidos o elevación asintomática de triglicéridos de grado 4
17. Cualquier condición (incluida eluso ilícito de drogas o abuso de alcohol) o resultados de laboratorio que en opinión del investigador puedan interderir en las evaluaciones y seguimiento del estudio
18. Historia o presencia de alergia a cualquiera de los componentes del medicamento en estudio |
|
| 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 |
? Mantenimiento de la supresión virológica (VIH-1 RNA <50 copias/ml) después de 48 semanas
? Cambio respecto valor basal en el colesterol total en la semana 48 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| 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 |
? Mantenimiento de la supresión virológica (VIH-1 RNA <50 copias/ml) a las 24 y 96 semanas
? Cambio respecto al basal en el recuento de CD4 a las 24, 48 y 96 semanas
? Cambio respecto al basal en el colesterol total a las 24 y 96 semanas
? Cambio respecto al basal en los valores de lípidos (LDL, HDL, triglicéridos y proporción TC:HDL) y registros Framingham y DAD a las 24, 48 y 96 semanas
? Seguridad (acontecimientos adversos clínicos y de laboratorio) a las 24, 48 y 96 semanas
? Cambio respecto al basal en los marcadores de inflamación, coagulación y disfunción endotelial a las 48 y 96 semanas
? Tolerancia (cuestionario EuroQoL) a las 24, 48 y 96 semanas |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 24, 48 and 96 weeks |
| 24, 48 y 96 semanas |
|
| 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 | 25 |
| 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
|
|
| 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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