E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008922 |
E.1.2 | Term | Chronic infection with HIV |
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 |
To evaluate the virological efficacy of maintainance therapy with atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression |
Valutare l’efficacia virologica di una terapia di mantenimento con atazanavir con ritonavir in combinazione con lamivudina in pazienti HIV positivi con precedenti esperienze di trattamento e con soppressione virologica completa e stabile. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy and the safety of atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression |
Valutare l’efficacia e la sicurezza di atazanavir con ritonavir in combinazione con lamivudina in pazienti HIV positivi con precedenti esperienze di trattamento e con soppressione virologica completa e stabile. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• HIV positive patients 18 years of age or older who signed an informed consent form
• On cART since no more than 3 years, without any treatment interruption.
• Treated with a cART regimen containing atazanavir boosted with ritonavir since at least 3 months
• With full virological suppression (VL<50 copies/mL) for a minimum of six months and in at least in two consecutive determination 3 months 2 weeks apart from each other
• With CD4 cell count >200 since at least 6 months and without opportunistic infections or other AIDS-related events since at least one year before screening |
• Pazienti HIV positivi di età maggiore o uguale a 18 anni che abbiano firmato un modulo di consenso informato
• In trattamento cART da non più di 3 anni, senza alcuna interruzione terapeutica.
• In trattamento con un regime cART contenente atazanavir potenziato con ritonavir da almeno 3 mesi
• Con soppressione virologica completa (VL<50 copie/mL) per un minimo di 6 mesi ed in almeno 2 valutazioni consecutive distanziate l’una dall’altra di 3 mesi 2 settimane
• Con conta dei linfociti CD4 >200 da almeno 6 mesi e senza infezioni opportunistiche o altri eventi AIDS-relati da almeno 1 anno prima dello screening |
|
E.4 | Principal exclusion criteria |
• Previous virological failure on a lamivudine- or PI-containing regimen or previous exposure to lamivudine-containing suboptimal antiretroviral regimens
• Patients with at least a single viral load blip over 200 copies/mL
• Patients with M184V or major atazanavir resistance mutation at previous genotypic resistance test (historical genotype)
• Pregnancy or lactation, planned pregnancy in the short-term
• Patients with HBsAg positive chronic HBV infection
• Patients who experienced major toxicities related to any of the study drugs in the past
• Patients with grade 4 laboratory abnormalities at baseline (excluding lipid profile).
• Patients with non-AIDS related illnesses which could, in the Clinician’s judgement, jeopardize the patient’s compliance to the study procedures (i.e. Child-Pugh B or higher liver cirrhosis, active cancers on treatment…).
• Patients treated with proton-pump inhibitors or other concomitant medication with potential for interactions reducing exposure to atazanavir |
• Precedenti fallimenti virologici durante un trattamento con lamivudina o PI o precedente esposizione a trattamenti antriretrovirali subottimali contenenti lamivudina
• Pazienti con almeno un singolo blip viremico al di sopra delle 200 copie/mL
• Pazienti con M184V o mutazioni maggiori di resistenza ad atazanavir in test genotipici eseguiti in precedenza (genotipo storico)
• Gravidanza o allattamento, pianificazione di una gravidanza a breve termine
• Pazienti con infezione cronica da HBV e positività dell’HBsAg
• Pazienti con precedenti esperienze di tossicità maggiori verso uno qualsiasi dei farmaci in studio
• Pazienti con anomalie di laboratorio di grado 4 al baseline (ad eccezione del profilo lipidico).
• Pazienti con malattie non-AIDS correlate che potrebbero, a giudizio del Curante, pregiudicare il rispetto delle procedure dello studio da parte del paziente (es. cirrosi epatica classificata come Child-Pugh B o superiore, neoplasie attive in trattamento…).
• Pazienti in trattamento con inibitori di pompa protonica o altri medicinali concomitanti con potenziali capacità di interazione con atazanavir ed in grado di ridurre l’esposizione al farmaco stesso. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of patients with viral load < 50 copies/mL at week 48 at the intention-to-treat with switch = failure analysis |
• Proporzione di pazienti con carica virale < 50 copie/mL alla settimana 48 all’analisi “intention-to-treat” con “switch = failure” |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Proportion of patients with viral load < 50 copies/mL at week 96 at the intention-to-treat with switch = failure analysis
• Time to loss of virological response (confirmed viral load rebound > 50 copies/mL) at survival intention-to-treat with switch = failure analysis at 48 and 96 weeks
• Proportion of patients with viral load < 50 copies/mL and time to loss of virological response at week 48 and 96 at the “as treated” analysis
• Proportion of patients with viral load < 50 copies/mL and time to loss of virological response at week 48 and 96 at the “per protocol” analysis
• Median increase of CD4 cell count during follow-up time
• Median changes in atazanavir through concentrations during follow-up time
• Median change in lipid (total cholesterol, HDL, LDL, TC/HDL ratio, triglycerides) and glucose and insulin levels during follow-up time
• Median change in renal function (creatinine, MDRD) during follow-up time
• Median change in bone density (hip and lumbar) at DEXA-scan and in markers of bone metabolism at weeks 24, 48, 72 and 96
• Median changes in upper and lower limb fat at DEXA-scan at 24, 48, 72 and 96 weeks
• Median changes in IMT and FMD at 24, 48 and 96 weeks
• Changes in the results of Neuropsychological tests at 48 and 96 weeks
• Changes in adherence and quality of life measured by validated questionnaires at 24, 48, 72 and 96 weeks |
• Proporzione di pazienti con carica virale < 50 copies/mL alla settimana 96 all’analisi “intention-to-treat with switch = failure”
• Tempo alla perdita della risposta virologica (rialzo viremico confermato > 50 copie/mL) all’analisi di sopravvivenza “intention-to-treat with switch = failure” a 48 e 96 settimane
• Proporzione di pazienti con carica virale < 50 copies/mL e tempo alla perdita della risposta virologica alle settimane 48 e 96 all’analisi “as treated”
• Proporzione di pazienti con carica virale < 50 copies/mL e tempo alla perdita della risposta virologica alle settimane 48 e 96 all’analisi “per protocol”
• Incremento mediano della conta dei linfociti CD4 nel periodo di follow-up
• Modifiche mediane della concentrazione di valle di atazanavir nel periodo di follow-up
• Modifiche mediane dei livelli di lipidi (colesterolo totale, HDL, LDL, rapporto TC/HDL, trigliceridi) e dei livelli di glucosio ed insulina nel periodo di follow-up
• Modifiche mediane della funzionalità renale (creatinina, MDRD) nel periodo di follow-up
• Modifiche mediane della densità ossea (femorale e lombare) alla DEXA e dei marcatori di metabolismo osseo alle settimane 24, 48, 72 e 96
• Modifiche mediane del grasso corporeo (upper e lower limb fat) alla DEXA a 24, 48, 72 e 96 settimane
• Modifiche mediane della IMT e FMD a 24, 48 e 96 settimane
• Modifiche nei risultati dei test neuropsicologici a 48 e 96 settimane
• Modifiche dell’aderenza e della qualità della vita misurate con questionari validati a 24, 48, 72 e 96 settimane |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
48 and 96 weeks |
48 E 96 settimane |
|
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 | 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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
stesso farmaco diversa combinazione |
same drug and different association |
|
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 | 22 |
E.8.5 | The trial involves multiple Member States | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | 0 |