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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008919 |
E.1.2 | Term | Chronic HIV 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 of this study is to compare the virological efficacy of switching HIV-1 infected participants virologically suppressed on a combination of a nucleoside/nucleotide reverse transcriptase inhibitor backbone (nRTI) with a ritonavir-boosted protease inhibitor (PI/r) to remain on their current combination (arm 1 or control) or switch to a PI/r with maraviroc (arm 2) or nRTI plus maraviroc (arm 3) for 90 weeks of follow-up. The primary comparison of interest is the proportion of patients with HIV RNA <200 copies/mL 48 weeks after randomisation in the maraviroc arms vs. control arm. |
|
E.2.2 | Secondary objectives of the trial |
A number of secondary outcomes will be assessed which are of relevance and interest in the assessment of the performance of the three study treatment regimens. These will include (but will not necessarily be limited to) virological, immunological, safety, clinical, metabolic, body composition changes, medication adherence and quality of life. |
|
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 |
A randomised, open‐label study to evaluate the efficacy and safety of maraviroc (MVC) as a switch for either nucleoside or nucleotide analogue reverse transcriptase inhibitors (N(t)RTI) or boosted protease inhibitors (PI/r) in HIV‐1 infected individuals with stable, well‐controlled plasma HIV‐RNA while taking their first N(t)RTI + PI/r regimen of combination antiretroviral therapy (cART): The Central nervous system Sub Study. Version 1.0 Primary Objective: To assess cerebral function parameters, changes in cerebral function parameters and differences in these changes between study treatment arms over 96 weeks in HIV-infected subjects stable on antiretroviral therapy randomised to 3 different treatment approaches.
A randomised, open‐label study to evaluate the efficacy and safety of maraviroc (MVC) as a switch for either nucleoside or nucleotide analogue reverse transcriptase inhibitors (N(t)RTI) or boosted protease inhibitors (PI/r) in HIV‐1 infected individuals with stable, well‐controlled plasma HIV‐RNA while taking their first N(t)RTI + PI/r regimen of combination antiretroviral therapy (cART): The Vascular Endothelium Sub Study. Version 1.0
Primary Objective: To determine the changes in the vascular endothelium in the three randomised arms as measured by changes in small and large arterial elasticity as measured by non invasive pulse wave tonometry plus changes in inflammatory & vascular biomarkers and coagulation (D-dimer) from baseline to 48 weeks.
|
|
E.3 | Principal inclusion criteria |
1. HIV-1 positive by licensed diagnostic test 2. Aged 18 years or older 3. HIV‐1 RNA <200 copies/mL plasma for at least 24 weeks 4. Stable (>24 weeks) ART including two N(t)RTIs and a PI/r 5. No evidence of any primary HIV genotypic mutations in HIV reverse transcriptase or protease for all patients with available resistance testing results conducted prior to cART and/or during viral rebound/failure 6. Able to provide written informed consent
|
|
E.4 | Principal exclusion criteria |
1. CXCR4 or CCR5/CXCR4 dual tropic HIV tropism or a non‐reportable tropism result based on assessment using proviral DNA 2. Anticipated need to modify current cART regimen for toxicity management in the next 6 months 3. The following laboratory variables: a) absolute neutrophil count (ANC) <750 cells/L b) hemoglobin <8.0 g/dL c) platelet count <50,000 cells/L d) ALT and AST >5 x ULN 4. Pregnant or nursing mothers 5. Patients with active viral hepatitis B infection 6. Use of immunomodulators within 30 days prior to screening 7. Hypersensitivity to soy or peanuts 8. Intercurrent illness requiring hospitalisation
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The comparison of the switch arms to control arm of proportions of participants with HIV RNA <200 copies/mL 48 weeks after randomisation in the intention-to-treat (ITT) population. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
A number of secondary endpoints will be examined at or through to week 48 in this protocol. These will include, but not be limited to the following: Virologic endpoints • Proportion of participants with plasma HIV RNA <50 copies/mL • Time to virological failure (defined as plasma HIV RNA ≥200 copies/mL on randomised therapy, on two occasions at least seven days apart) • Time to loss of virological response, as defined by virological failure, permanent discontinuation of randomised treatment, new AIDS-defining illness, death or withdrawal from the study • Changes from baseline in log plasma HIV RNA copies/mL • Frequency of plasma HIV RNA blips (defined as a plasma viral load result >200 copies/mL on randomised therapy following a previous result <200 copies/mL, with a follow-up result <200 copies/mL at least seven days after the >200 copies/mL reading, in the absence of a change of any component of the ART regimen). Immunologic and biomarker endpoints • Changes from baseline in absolute and percentage CD4+ T cells • Changes from baseline in selected soluble markers of immune activation/coagulation. Clinical endpoints • Rate of opportunistic disease (AIDS) or death • Rates of Serious Non-AIDS-defining illness and Non-AIDS-related mortality. Metabolic and body composition endpoints • Changes from baseline in fasting lipids (TC, LDL-c, HDL-c and TG) • Changes in absolute CVD risk assessment using the Framingham risk equation • Changes from baseline in fasting glucose and insulin • Rates of initiation or changes in existing lipid-lowering therapies • Changes from baseline in anthropometric changes derived from Dual-energy X-ray absorptiometry (DXA) scanning of peripheral and central adipose tissue • Changes from baseline in bone mineral density as measured by DXA • Changes in 10-year fracture risk using the FRAX® algorithm • Changes from baseline in markers of bone turnover. Safety • Changes from baseline in selected serum biochemical parameters, including changes in estimated glomerular filtration rate • Proportions experiencing and types of SAEs • Proportions experiencing, types and severity of AEs. Adherence • Self-reported adherence to randomised study medications. Quality of Life • Change from baseline health status scores as measured by the SF-12 health status. Resistance endpoints • Patterns of genotypic resistance at virological failure.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Argentina |
Australia |
Canada |
Chile |
France |
Germany |
Ireland |
Mexico |
Poland |
Spain |
Thailand |
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
|
The trial will be completed when all patients have attended for 96 weeks of follow-up, unless the DSMB have ceased the study early due to safety or tolerability concerns. |
|
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 |