| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus Type 1 |
| Virus dell¿immunodeficienza umana di 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 | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068341 |
| E.1.2 | Term | HIV-1 infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 primary objective is to demonstrate noninferiority in efficacy of a
D/C/F/TAF containing once-daily single-tablet regimen versus
DRV/COBI FDC combined with FTC/TDF FDC in HIV-1 infected, ARV
treatment-na¿ve adult subjects, as determined by the proportion of
virologic responders defined as having HIV-1 RNA <50 copies/mL at
Week 48 (FDA-defined snapshot analysis), with a maximum allowable
difference of 10%. |
| L'obiettivo primario ¿ dimostrare la non inferiorit¿ a livello di efficacia di una compressa con combinazione a dosaggio fisso (FDC) di D/C/F/TAF rispetto alla FDC di darunavir/cobicistat (DRV/COBI) somministrata in concomitanza alla FDC di emtricitabina/tenofovir disoproxil fumarato (FTC/TDF) in soggetti adulti infetti da virus dell'immunodeficienza umana di tipo 1 (H1V-1), mai sottoposti a trattamento con farmaci antiretrovirali (ARV), come determinato dalla proporzione di responder virologici, ossia con HIV-1 RNA <50 copie/ml alla Settimana 48 (analisi istantanea definita da FDA), con una differenza massima ammissibile del 10%. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate superiority of a D/C/F/TAF once-daily single-tablet regimen
vs DRV/COBI FDC combined with FTC/TDF FDC as determined by having
HIV-1 RNA <50 copies/mL at Week 48 (FDA-defined snapshot analysis),
in case noninferiority is established
*to evaluate the immunologic response (CD4+ cell count) of the 2
treatment arms through Week 48
*to evaluate long-term efficacy and safety of the D/C/F/TAF regimen
(until Week 96 and beyond)
*to evaluate the incidence of grade 3 and 4 AEs, serious adverse events
(SAEs), and premature discontinuations due to AEs in the 2 treatment
arms through Week 48
*to evaluate the change from baseline in serum creatinine, eGFR based
on creatinine clearance and eGFR based on cystatin C clearance in the 2
treatment arms at Week 48
*to evaluate the change from baseline in renal biomarkers at Week 48;
*to assess the development of viral resistance in the 2 treatment arms
through Week 48;
*to evaluate the steady-state pharmacokinetics of DRV and TAF. |
-Valutare la superiorit¿ di una cp con D/C/F/TAF rispetto a DRV/COBI somministrata con FTC/TDF come determinato dalla proporz. di responder virologici, alla Set. 48, se stabilita la non inferiorit¿.
-Valutare la risposta immunologica dei 2 bracci di trattamento alla Set. 48. -Valutare l'efficacia, la resistenza e la sicurezza a lungo termine del regime con FDC di D/C/F/TAF (Set. 96 e successive).
-Valutare l'incidenza di EA di grado 3 e 4, di EAS e le interruzioni anticipate a causa di EA nei 2 gruppi di trat. alla Set. 48. -Valutare la variazione rispetto alla baseline della creatinina nel siero, della velocit¿ di filtrazione glomerulare stimata (eGFR) sulla base della clearance della creatinina e la eGFR basata sulla clearance della cistatina C nei 2 bracci di trat. alla Set. 48.la variazione rispetto dal baseline dei biomarcatori renali alla Set.48, lo sviluppo della resistenza virale nei 2 bracci di trat. fino alla Set.48 e la farmacocinetica allo steady-state di DRV e TAF. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subject must be antiretroviral (ARV) treatment-naive (never treated with an ARV including post-exposure phophylaxis and pre-exposure phophylaxis); no prior use of
any approved or experimental anti- human immunodeficiency virus
(anti-HIV) drug for any length of time. Subjects treated with postexposure
prophylaxis and/or pre-exposure prophylaxis may be enrolled
in the study if treatment stopped at least 30 days prior to Screening
- Screening plasma HIV-1 ribonucleic acid (RNA) level greater than or
equal to >=1,000 copies per milliliter (copies/mL)
- Cluster of Differentiation 4+ (CD4+) cell count =70 cells/microliter
(cells/mcL)
- Screening HIV-1 genotype report must show full sensitivity to DRV,
TDF and FTC
- Screening eGFRcreatinine >=50 mL/min according to the Cockcroft-
Gault formula for creatinine clearance |
I soggetti devono essere naive al trattamento antiretrovirale (ARV) (non devono mai essere stati sottoposti a trattamento ARV, incluso la profilassi pre e post-esposizione); nessun utilizzo precedente di farmaci anti-HIV approvati o sperimentali per qualsiasi lasso di tempo; i soggetti trattati con profilassi post-esposizione e/o profilassi pre-esposizione possono essere arruolati nello studio se il trattamento è stato interrotto almeno 30 giorni prima dello screening.
-Livelli RNA HIV-1 nel plasma allo screening = 1.000 copie/ml.
-Conta cellulare CD4+ > 50 cellule/µL.
-Il report del genotipo HIV-1 allo screening deve mostrare completa sensibilità a DRV, TDF e FTC.
-eGFRcreatinina allo screening =70 ml/min secondo la formula Cockcroft-Gault per clearance della creatinina
|
|
| E.4 | Principal exclusion criteria |
Subject has been diagnosed with a new acquired immunodeficiency
syndrome (AIDS)-defining condition within the 30 days prior to
screening
- Subject has proven or suspected acute hepatitis within 30 days prior to
screening
- Subject is hepatitis C or hepatitis B positive
- Subject has a history of cirrhosis |
Al soggetto è stata diagnosticata una nuova condizione di definizione dell'AIDS (vedere Allegato 2) entro 30 giorni dallo screening.
Il soggetto presenta epatite acuta dimostrata o sospetta entro 30 giorni prima dello screening.
Il soggetto è positivo agli anticorpi dell'epatite C o B;
Il soggetto ha una storia di cirrosi.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Percentage of Participants With Human
Immunodeficiency Virus (HIV) -1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies per Milliliter
(copies/mL) defined by FDA Snapshot Approach
|
L'endpoint di efficacia primaria è la percentuale di soggetti con HIV-1 RNA <50 copie ml alla
Settimana 48 come definito dall'analisi istantanea della FDA. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1) Percentage of Participants With HIV-1
RNA Less Than (<) 50
Copies/mL by FDA Snapshot Approach
2) Percentage of Participants With HIV-1 RNA Less Than (<) 50
Copies/mL Defined by the Time to Loss of Virologic Response (TLOVR)
Algorithm
3) Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell
Count at Week 48 and 96
4) Percentage of Participants With Resistance to antiretrovirals (ARVs)
and Type of Resistance in Participants with Virologic Failure
5) Change From Baseline in Serum Creatinine, eGlomerular Filteration
Rate-Creatinine (eGFR Creatinine) and eGFR Cystatin C at Week 48 and
96
6) Percentage of Participants Experiencing Grade 3 and 4 Adverse Events
(AEs), Serious
Adverse Events (SAEs), and Premature Discontinuations due to AEs
7) Change From Baseline in Renal Biomarkers at Week 48 and 96
8) Percent Change From Baseline in Spine and Hip Bone Mineral Density
(BMD) at Weeks 24, 48 and 96 |
1)La percentuale di soggetti con HIV-1 RNA <50 copie/ml come definito dall'analisi istantanea della FDA.
2)La percentuale di soggetti con HIV-1 RNA , <50 e copie/ml come definito dall'algoritmo del
tempo alla perdita di risposta virologica (TLOVR).
3)La variazione dalla baseline nella conta cellulare CD4+ alle Settimane 48 e 96.
4) La percentuale di soggetti con fallimento virologico che sviluppano resistenza virale e il tipo di resistenza alle Settimane 48 e 96.
5)La variazione dalla baseline nei valori di creatinina sierica, eGFRcreatinina (tramite Cockcroft-Gault e CKD-EPI) e eGFRcistatinaC
6)La percentuale di soggetti che manifestano AE di grado 3 e 4, SAE e interruzioni anticipate a causa di AE alle Settimane 48 e 96.
7)La variazione dalla baseline nei biomarcatori renali alle Settimane 48 e 96.
8) La percentuali di cambiamento dal baseline nella densit¿ minerale ossea nella schiena e nei fianchi alle settimane 24, 48 e 96
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 96
2) Week 48 and 96
3) Baseline, Week 48 and 96
4) Up to Week 48 and 96
5) Baseline, Week 48 and 96
6) Up to Weeks 48 and 96
7) Baseline, Week 48 and 96
8) Baseline, Week 24, 48 and 96 |
1) Settimana 96
2) Settimana 48 e 96
3) Baseline, settimana 48 e 96
4) Fino alla settimana 48 e 96
5) Baseline, settimana 48 e 96
6) Fino alle settimane 48 e 96
7) Baseline, settimana 48 e 96
8) Baseline, settimana 24, 48 e 96 |
|
| 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 | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| DRV/COBI FDC somministrato con FTC/TDF FDC |
| DRV/COBI FDC coadministered with FTC/TDF FDC |
|
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 62 |
| 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 |
| Canada |
| Russian Federation |
| United States |
| Belgium |
| France |
| Germany |
| Italy |
| Poland |
| Spain |
| United Kingdom |
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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