| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| subject whith PHI never treated |
| Infezione primaria da HIV (PHI) |
|
| E.1.1.1 | Medical condition in easily understood language |
| subject whith PHI never treated |
soggetti risultati positivi al test HIV e che non hanno
ancora assunto nessun farmaco antiretrovirale |
|
| 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 | PT |
| E.1.2 | Classification code | 10000807 |
| E.1.2 | Term | Acute 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 primary end point will be the change in total HIV-DNA level from baseline to 48 weeks |
| L’obiettivo primario è la variazione nei livelli di HIV DNA dal baseline alla settimana 48. |
|
| E.2.2 | Secondary objectives of the trial |
• long-term virological efficacy;
• safety;
• viral reservoirs: HIVDNA in PBMC, anal brushing, nasal brushing and HIVRNA in cerebrospinal fluid (CSF) ;
• pharmacokinetic (Ctrough) on plasma and PBMC, anal and nasal brushing and cerebrospinal fluid (CSF), lymph nodes and GALT;
• genetic markers: HLA-A, HLA-B, HLA-C;
• variation in immunological parameters;
• variation in inflammation and immune-activation markers;
• variation in T-cells, B-cells and DC-phenotypes;
• variation of viral tropism.
|
- Efficacia virologica a lungo termine
- Tollerabilità
- Serbatoi: HIV DNA in PBMCs, liquor cefalorachidiano e cellule anali
- Farmacocinetica su plasma e PBMCs, liquor cefalorachidiano, cellule anali, tampone nasale, linfonodi e GALT
- Markers genetici: HLA-A, HLA-B, HLA-C
- Variazione nei parametri immunologici e infiammatori
- Variazione in cellule B, T e DC
- Variazione del tropismo virale
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies
Specify title, date and version of each substudy with relative objectives: Neurological, GALT (Gut-Associated Lymphoid Tissue Colorectal Biopsy) and Lymphnodes, version 2.0 1 February 2017, objective: pharmacokinetic and HIV RNA in cerebrospinal fluid, GALT and lymphnodes
|
Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sottostudi Neurologico, GALT (biopsia colorettale di tessuto linfoide associato all'intestino) e Linfonodi, version 2.0 1 febbraio 2017, obiettivi: farmacocinetica e HIV RNA su liquido cefalorachidiano, GALT e linfonodi
|
|
| E.3 | Principal inclusion criteria |
- Subjects must be at least 18 years of age at the time of randomization, of either sex and of any race.
- Primary HIV Infection defined according to Fiebig’s classification.
- Subjects must have given written informed consent and must be able to adhere to dose and visit schedules.
- Female subjects of child-bearing potential must agree to use a medically accepted method of contraception.
- Female subjects of child-bearing potential must have a negative serum beta-hCG pregnancy test at Screening, and a negative urine beta-HCG pregnancy test on Day 1 prior to dosing.
A female, may be eligible to enter and participate in the study if she:
a is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and = 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy;
a. is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
• Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
• Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
• Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see Appendix 4 for an example listing of approved IUDs);
• Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject;
• Approved hormonal contraception for subjects randomized to arm B (TDF/FTC + DTG) (see Appendix 4 for a listing of examples of approved hormonal contraception)
• Approved hormonal contraception and a barrier method for subjects randomized to arm A (TDF/FTC +DRV/cobicistat) and C (TDF/FTC +DRV/cobicistat +DTG)
• Any other method with published data showing that the expected failure rate is <1% per year.
Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of IP. Approved hormonal contraception for subjects randomized to the treatment groups should be specified.
|
- I soggetti devono avere almeno 18 anni di età al momento della randomizzazione, di entrambi i sessi.
- L'infezione primaria da HIV deve essere definita secondo la classificazione di Fiebig.
- I soggetti devono aver dato il consenso informato scritto e devono essere in grado di aderire al calendario visite stabilito.
- I soggetti di sesso femminile in età fertile devono accettare di utilizzare un metodo di contraccezione clinicamente accettato.
- Soggetti di sesso femminile in età fertile devono avere un test negativo di beta-hCG nelle urine allo screening, e un test negativo di beta-HCG nelle urine il giorno prima del dosaggio.
|
|
| E.4 | Principal exclusion criteria |
- Female subjects of childbearing potential who are breastfeeding, pregnant, or planning to become pregnant.
- Subjects with active opportunistic infection or malignancy.
- Subjects positive for Hepatitis B at screening (HBsAg+), or anticipated need for Hepatitis C virus (HCV) therapy during the study.
- Subjects with known liver cirrhosis.
- Subjects with any clinically significant condition or situation other than the condition being studied that, in the opinion of investigator, would interfere with the study evaluations or optimal participation.
- Subjects with allergy/sensitivity to drugs or its excipients.
- History or presence of allergy to the study drugs or their components
- Alanine aminotransferase (ALT) ¿5 times the upper limit of normal (ULN), OR ALT ¿3xULN and bilirubin ¿1.5xULN (with >35% direct bilirubin)
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
- Subject has creatinine clearance of <70 mL/min via Cockroft-Gault method
- Hepatic failure (Child-Plug grade C)
- Use of not modifiable concomitant drugs: carbamazepine, fenitoine, fenobarbital, rifampicine, Hypericum perforatum, dofelitide.
|
- Soggetti di sesso femminile in età fertile, o in stato di gravidanza, o in allattamento, o che stanno pianificando una gravidanza.
- Soggetti con infezione opportunistica attiva.
- Soggetti positivi per l'epatite B allo screening (HBsAg positivo), o soggetti con necessità di Terapia per il virus dell'epatite C (HCV) durante lo studio.
- Soggetti con nota cirrosi epatica.
- Soggetti con qualsiasi condizione clinicamente significativa o con situazioni che potrebbero interferire con le valutazioni dello studio o con una partecipazione ottimale ad esso.
- Soggetti con allergia / sensibilità ai farmaci o ai loro eccipienti.
- Soggetti con storia o presenza di allergia ai farmaci in studio o ai loro componenti.
- Alanina aminotransferasi (ALT) ¿5 volte il limite superiore del valore normale (ULN), o ALT ¿3xULN e bilirubina ¿1.5xULN (con bilirubina diretta> 35%).
- Malattie epatiche instabili (come definito dalla presenza di ascite, encefalopatia, coagulopatia, ipoalbuminemia, esofagea o varici gastriche, o ittero persistente), cirrosi, noti anomalie biliari (con l'eccezione della sindrome di Gilbert o calcoli biliari asintomatici).
- Soggetti con insufficienza epatica grave (classe C), come determinato dalla classificazione Child-Pugh.
- Soggetti con clearance della creatinina <70 mL / min tramite metodo di Cockroft-Gault.
- Pazienti con grave compromissione epatica (Classe C di Child-Pugh).
-Cosomministrazione non modificabile dei seguenti farmaci: carbamazepina, fenobarbital, fenitoina, rifampicina, Erba di San Giovanni, dofetilide
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary end point will be the change in total HIV-DNA level from baseline to 48 weeks. |
| Variazione dell’HIV-DNA alla settimana 48. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• time to achieve undetectable viral load (HIV-1 RNA <50 copies/mL);; • change in HIV-DNA at week 12 and 48;; • change from baseline in CD4+, CD4%, CD8+, CD8%, CD4/CD8 at week 48; • proportion of patients with CD4/CD8>1 at week 48;; • change in HIV-1 RNA at week 12 in CSF; • change in in nasal brushing HIV DNA at week 12 and 48
• change in anal brushing HIV DNA at weeks 12 and 48
; - Correlazione della concentrazione dei farmaci (TAF, FTC, DRV/c, DTG) con la risposta virologica; • correlation of PBMC, CSF, lymph nodes, anal brushing, nasal brushing and GALT concentrations (TDF, FTC, DRV/c and DTG) with virological decay and persistent virus; • change from baseline in T cells subpopulation at week 12 and 48;
• change from baseline in B cells population at week 12 and 48;
• change from baseline in DC phenotype at week 12 and 48
; • change from baseline in inflammation and immune-activation markers at week 12 and 48; • change from baseline in microbioma at week 48; • proportion of patients with AEs (clinical and laboratory), proportion of patients who discontinued and reasons for treatment discontinuation (e.g. due to AE/Loss of viral control/Death/Patient decision); - Proporzione di pazienti con gli stessi alleli HLA-A, HLA-B e HLA-C; • proportion of patients with HIV-1 RNA <50 copies/mL at week 12, 24 and week 48; |
| - Tempo per raggiungere HIV-1 RNA <50 copies/mL;; - Variazione dell’HIV DNA alle settimane 12 e 48; - Variazione dalla baseline in CD4+, CD4%, CD8+, CD8%, CD4/CD8 alla settimana 48; - Proporzione di pazienti con CD4/CD8>1 alla settimana 48; - Variazione di HIV-1 RNA nel liquor alla settimana 12; - Variazione di HIV DNA nelle cellule anali e tampone nasale alle settimane 12 e 48; • correlation of plasma drugs concentration (TDF, FTC, DRV/c, DTG) with virological decay; - Correlazione delle concentrazioni (TDF, FTC, DRV/c, DTC) con la risposta virologica e la persistenza del virus nelle PBMC, liquido cefalo rachidiano, linfonodi, cellule anali, tampone nasale e campione colorettale di tessuto linfoide associato all'intestino; - Modifica delle sottopopolazioni B, T e DC alle settimane12 e 48;; - Modifica dei markers infiammatori alle settimane12 e 48; - Modifica del microbioma alla settimana 48; - Proporzione di pazienti con eventi avversi clinici e di laboratorio; • proportion of patients with same alleles HLA-A, HLA-B and HLA-C; - Proporzione dei pazienti con HIV-1 RNA <50 copies/mL alla settimana 12, 24 e 48; |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
necessary time period; week 12 and 48; week 48; week 48; week 12; settimane 12 e 48; indefinite; indefinite; week 12 and 48; week 12 and 48; week 48; indefinite; indefinite;
week 12, 24 and 48 |
| tempo necessario; settimana 12 e 48; settimana 48; settimana 48; settimana 12; settimane 12 e 48; indefinito; indefinito; settimane 12e 48; settimane 12 e 48; settimana 48; indefinito; indefinito; settimana 12, 24 e 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
CHANGE IN HIV DNA IN VIRAL RESERVOIR, IMMUNOLOGICAL
INFLAMATATORY MARKERS, CHANGE IN TROPISM, |
HIV DNA nei santuari HIV, parametri immunologici, parametri infiammatori e di attivazione
immunitaria, fentotipizzazione cellule T, B e DC, variazione tropismo virale |
|
| 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 |
| altra combinazione di IMP |
| altra combinazione di IMP |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 28 |
| 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 | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| 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 |
Print
