| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus Type 1 |
| Virus de la Inmunodeficiencia Humana Tipo 1 |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 17.1 |
| 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 |
|
| 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 |
| The purpose of this study is to demonstrate non-inferiority in efficacy while switching to a once-daily single-tablet regimen containing darunavir (DRV)/ cobicistat (COBI)/ emtricitabine (FTC)/ tenofovir alafenamide (TAF) (D/C/F/TAF tablet) relative to continuing the current regimen consisting of a boosted protease inhibitor (bPI) combined with tenofovir disoproxil fumarate (FTC/TDF) in virologicallysuppressed (human immunodeficiency virus type 1 ribonucleic acid [HIV-1 RNA] concentrations less than [<] 50 copies per milliliter [copies/mL]) HIV-1 infected participants. |
El objetivo de este estudio es demostrar la no inferioridad en cuanto a la
eficacia del cambio de tratamiento a un régimen en un solo comprimido
administrado una vez al día de D/C/F/TAF frente a la continuación del
régimen actual formado por un IPp combinado con FTC/TDF en sujetos
infectados por el virus de la inmunodeficiencia humana de tipo 1 (VIH 1)
con supresión virológica (ARN del VIH-1 < 50 copias/ml), en cuanto a la
proporción de sujetos con respuesta virológica definida como un ARN del
VIH 1 <50 copias/ml. |
|
| E.2.2 | Secondary objectives of the trial |
- To demonstrate noninferiority of switching to a D/C/F/TAF once-daily single-tablet regimen versus continuing the current bPI combined with FTC/TDF at Week 48;
- To evaluate superiority of switching to a D/C/F/TAF once-daily single-tablet regimen versus continuing the current bPI combined with FTC/TDF at Weeks 24 and 48, in case noninferiority is established;
- To evaluate the durability of the antiviral efficacy of the 2 treatment arms through Week 48;
- To evaluate the immunologic response of the 2 treatment arms through Weeks 24 and 48;
- To evaluate the incidence of grade 3 and 4 Adverse Events (AEs), serious adverse events, premature discontinuations due to AEs in the 2 treatment arms through Weeks 24 and 48;
- To evaluate the change from baseline in serum creatinine, eGFR for creatinine clearance in the 2 treatment arms at Weeks 24 and 48;
- To evaluate the change from baseline in renal biomarkers at Weeks 24 and 48; |
-Demostrar no inferioridad del cambio de tratamiento a D/C/F/TAF
frente al régimen de IPp combinado con FTC/TDF en la semana 48
-Evaluar superioridad del cambio de tratamiento a un régimen de 1
comprimido/ 1 vez al día de D/C/F/TAF frente al régimen de IPp
combinado con FTC/TDF, determinada en semana 24 y 48 en caso de establecerse la no inferioridad.
-Evaluar durabilidad de la eficacia antiviral de los 2 grupos de
tratamiento hasta la semana 48
-Evaluar respuesta inmunitaria de los 2 grupos de tratamiento hasta las
semanas 24 y 48
-Evaluar incidencia de AA grado 3 y 4, acontecimientos adversos graves
(AAG) y retiradas prematuras debido a AA en los 2 grupos de tratamiento hasta las semanas 24 y 48.
-Evaluar la variación respecto al valor basal de la creatinina sérica, la
FGe para el aclaramiento de la creatinina ,FGecr en los 2 grupos de
tratamiento en las semanas 24 y 48
-Evaluar la variación respecto al valor basal de los biomarcadores
renales en las semanas 24 y 48. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Currently being treated with a stable antiretroviral (ARV) regimen consisting of a boosted protease inhibitor (limited to darunavir [DRV] or atazanavir with low-dose ritonavir [rtv] or cobicistat [COBI], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) only, for at least 6 consecutive months preceding the Screening visit. Participants treated with the combination of DRV + COBI + FTC/TDF and completing the GS-US-216-0130 (NCT01440569) study, and who are fulfilling the present protocol criteria, will be given the option to participate in this study;
- On-treatment plasma human immunodeficiency virus type 1 ribonucleic acid (HIV-1 RNA) concentrations less than (<) 50 copies per milliliter (copies/mL) or HIV-1 RNA undetectable by a local HIV-1 RNA test for at least 6 consecutive months prior to the Screening visit and have HIV-1 RNA <50 copies/mL at the Screening visit;
- A single virologic elevation of greater than or equal to (>=) 50 copies/mL after previously reaching viral suppression within 6 months prior to Screening is acceptable, provided a subsequent test prior to Screening was <50 copies/mL
- Absence of history of failure on DRV treatment and absence of DRV resistance-associated mutations (RAMs), if documented historical genotypes are available
- Normal electrocardiogram (ECG) at Screening (or if abnormal, determined by the Investigator to be not clinically significant) |
1.Tratamiento actual con un régimen ARV estable consistente en un IPp
(limitado a DRV o ATV con rtv o COBI, o LPV con rtv) combinado con solo
FTC/TDF durante al menos 6 meses consecutivos anteriores a la visita de
selección.
-Los sujetos tratados con la combinación de DRV + COBI + FTC/TDF que
completen el estudio GS US 216 0130 que cumplan los criterios del
protocolo actual, tendrán también la posibilidad de participar en este
estudio.
2.Concentraciones plasmáticas del VIH 1 <50 copias/ml o ARN del VIH 1
indetectable en un análisis local del ARN del VIH 1 durante al menos 6
meses previos a la visita de selección y un ARN del VIH 1 <50 copias/ml
en la visita de selección.- Se acepta una única elevación virológica (< = )50 copias/ml después de haber alcanzado la supresión viral en los 6 meses previos a la selección, siempre que en un análisis posterior realizado antes de la selección se hayan obtenido <50 copias/ml.
3.Ausencia de un fracaso previo durante el tratamiento con DRV y
ausencia de MAR a DRV si se dispone de genotipos históricos
documentados.
4.ECG normal en la selección (o si es anormal, el investigador determina
que no es clínicamente significativo). |
|
| E.4 | Principal exclusion criteria |
- A new acquired immunodeficiency syndrome (AIDS) - defining condition diagnosed within the 30 days prior to Screening
- Proven or suspected acute hepatitis within 30 days prior to study entry
- Hepatitis C antibody positive; however, participants previously cured of hepatitis C virus (HCV) infection, with documented sustained virologic response, that is, undetectable HCV RNA 24 weeks after the last dose of HCV treatment, are allowed to participate
- Hepatitis B surface antigen (HBsAg) positive
- Participants with cirrhosis as diagnosed based on local practices. As conventional ultrasound might not allow to adequately rule out liver cirrhosis, the use of other means for specific liver fibrosis staging is preferred |
1.Una nueva enfermedad definitoria de SIDA diagnosticada en los 30
días previos a la selección.
2.Hepatitis aguda confirmada o sospechada en los 30 días previos a la
inclusión en el estudio.
3.Anticuerpos positivos para la hepatitis C; no obstante, se permitirá la
participación de sujetos previamente curados de una infección por el
virus de la hepatitis C (VHC), con documentación de respuesta virológica
sostenida, es decir, ARN del VHC indetectable 24 semanas después de la
última dosis del tratamiento contra el VHC.
4.Anticuerpos positivos contra el antígeno de superficie del virus de la
hepatitis B (HBsAg).
5.Sujetos con cirrosis diagnosticada conforme a la práctica local.
-Como las ecografías convencionales no siempre permiten descartar
debidamente una cirrosis hepática, se prefiere el uso de otros medios
para determinar el estadio específico de fibrosis hepática. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Number of Participants With Plasma Human Immunodeficiency Virus - 1 (HIV-1) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 per FDA Snapshot Approach |
Proporción de pacientes con un ARN del VIH 1 <50 copias/ml en la semana
48, según el análisis FDA snapshot |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1 - Number of Participants With Plasma HIV-1 RNA Level <50 Copies/mL at Week 48 and 96 per FDA Snapshot Approach
2 - Number of Participants With Plasma HIV-1 RNA Level <50 Copies/mL at Weeks 24, 48, and 96 per TLOVR algorithm
3 - Change From Baseline in Cluster of Differentiation (CD) 4+ Cell Counts at Week 24, 48, and 96
4 - Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) of Grade 3 and 4, and Premature Discontinuations due to AEs
5 - Change From Baseline in Serum Creatinine, Estimated Glomerular Filtration Rate for Creatinine Clearance (eGFRcr), and eGFR for Cystatin-C Clearance (eGFRcyst) at Week 24 and 48
6 - Change From Baseline in Renal Biomarkers at Week 24 and 48 |
- Proporción de pacientes con un ARN del VIH 1 <50 copias/ml en la
semana 48 y 96, según el análisis FDA snapshot
- Proporción de pacientes con un ARN del VIH en plasma <50 copias/ml en la
semana 24, 48 y 96, según el algoritmo del tiempo hasta la desaparición
de la respuesta virológica (THDRV).
- Variación media del recuento de linfocitos CD4+ con respecto al valor
basal en las semanas 24 , 48 y 96
- Proporción de sujetos que experimentan AA de grado 3 y 4, AAG e
interrupción prematura debido a AA hasta las semanas 24 y 48.
- Variación respecto al valor basal de la creatinina sérica, la FGecr
(mediante Cockcroft-Gault y CKD-EPI) y la FGecist (mediante CKD-EPI)
en las semanas 24 y 48.
- Variación respecto al valor basal de los biomarcadores renales en las
semanas 24 y 48. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - Week 48, 96
2 - Week 24, 48, and 96
3 - Baseline, Week 24, 48, and 96
4 - Baseline up to Week 48
5 - Baseline, Week 24, 48
6 - Baseline, Week 24, 48 |
1- Semana 48,96
2- Semana 24, 48 y 96
3- Basal, semana 24, 48 y 96
4- Basal hasta semana 48
5- Basal, semena 24, 48
6- Basal, semana 24,48 |
|
| 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 | 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) | 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.8.2.4 | 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 | 17 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 76 |
| 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 | No |
| 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 |
| Belgium |
| Canada |
| France |
| Germany |
| Netherlands |
| Poland |
| Romania |
| Russian Federation |
| Spain |
| Sweden |
| Switzerland |
| United Kingdom |
| United States |
|
| 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
|
| LVLS |
| Última visita del último paciente |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| 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 | 14 |
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