E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10052740 |
E.1.2 | Term | Acquired immunodeficiency syndromes |
|
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 |
1. To describe and compare the kinetics of immune recovery degree and quality in advanced naive HIV-infected individuals (CD4+ 50-150 cells/l) starting as first regimen an EFV-based HAART regimen compared to less advanced patients (CD4+>250 cells/l) 2. To thoroughly characterise the role and kinetics of specific immune parameters in immune reconstitution following EFV-based HAART |
|
E.2.2 | Secondary objectives of the trial |
1. To describe the kinetics of HIV-RNA decay in plasma of patients of the two groups 2. To describe the kinetics of intracellular HIV DNA in total peripheral blood CD4 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- male or female subject 18 to 50 years of age inclusive; - the subject should be able to understand and comply with protocol requirements, instruction and protocol-stated restrictions; - signed and dated written informed consent form prior to admission to the study; - HIV positive status tested with ELISA and confirmed by Western Blot; - documented CD4+ T cell count between 50 and 150/l (advanced) - documented CD4+ T cell count > 250/l (less advanced); - genotypic test allows study drugs; - no prior or current use of antiretroviral therapy; - no current opportunistic infection (at least 2 weeks must have passed from the end of the therapy for OI); - no current use of systemic or inhaled steroids within the prior two months; - no current use of immune modulating agents, HIV immunotherapeutic agents or vaccines; - if female, be neither pregnant nor breastfeeding, and willing to use two methods of contraception (physical and hormonal double barrier method) throughout the duration of the study or be menopausal or of non-child bearing potential. All subjects should have been advised on practice of safe sex. |
|
E.4 | Principal exclusion criteria |
- in the investigators opinion subject who is unlikely to comply with the protocol and complete the study; - primary HIV-1 infection; - current opportunistic infection; - genotypic test not allowing the study drugs; - subject with current abuse of alcohol (>21 units/week or >3 units/day for males; >14 units/week or >2 units/day for females [1 unit is equivalent to half-pint (220 ml) of beer or 1 (25 ml) measure of spirits or 1 glass (125 ml) of wine] or illicit drug use; - current use of immune modulating agents or HIV immunotherapeutic vaccines; - current use of natural or herbal therapies; - current use of systemic or inhaled steroids and/or use of these therapies within the two months prior to enrolment; - pregnant or lactating female; - subject with any of the following laboratory results within 14 days prior to the first dose of the antiretroviral treatment: - haemoglobin concentration < 10 mg/dl for men and < 9.0 mg/dl for women; - neutrophil count < 1000 cells/mm3; - platelet count < 75,000 cells/mm3; - AST and ALT > 2.5 times upper to the normal value; - serum creatinin > 2 times upper to the normal value; - Karnofsky index < 50. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variables of the study are: - proportion of subjects who have a CD4+ T cell number increase > 20% after 24 weeks of EFV-based HAART; - changes from baseline of peripheral CD4+ and CD8+ T-cell activation and proliferation rates; - changes from baseline of peripheral CD4+ and CD8+ apoptosis rate; - changes from baseline of levels and function of interleukin-7 (IL-7) and interleukin-15 (IL-5), as T-cell homeostasis cytokine regulators; - frequency of circulating HIV-specific IFN-&#61543; and IL-2 producing T-cells; - frequency of circulating HIV-specific CD8+ IFN-&#61543; ELISPOT responses; - frequency of circulating T-regulatory CD4+ T cells (Treg); - changes from baseline of patterns of CD4 and CD8 T-cell maturation |
|
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 | No |
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 | No |
E.8.1.2 | Open | No |
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 in due popolazioni di pz HIV-pos |
|
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 | 4 |
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
|
Ultima visita dell`ultimo soggetto inserito nella sperimentazione |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |