E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Increases in inflammatory biomarkers have been associated with various non-AIDS complications such as cardiovascular events. Maraviroc has no known toxic effects on mitochondria and has been shown to reduce immune activation / inflammation in treatment intensification settings. The purpose of this study is to investigate if switching from NRTIs to Maraviroc results in reversal of NRTI-associated mitochondrial toxicity and decreases in markers of immune activation and inflammation.
|
|
E.1.1.1 | Medical condition in easily understood language |
This study wants to investigate if switching from NRTIs to Maraviroc results in reversal of NRTI-associated mitochondrial toxicity and decreases in markers of immune activation and inflammation. |
|
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 | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053961 |
E.1.2 | Term | Mitochondrial toxicity |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008919 |
E.1.2 | Term | Chronic 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 |
- Effect of Switching from NRTIs to Maraviroc on markers of mitochondrial toxicity - Effect of Switching from NRTIs to Maraviroc on markers of immune activation
|
|
E.2.2 | Secondary objectives of the trial |
- Effect of Switching from NRTIs to Maraviroc on inflammatory markers - Effect of Switching from NRTIs to Maraviroc on virological and immunological control - Effect of Switching from NRTIs to Maraviroc on proximal renal tubular function - Effect of Switching from NRTIs to Maraviroc on safety |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or menopausal female subjects, aged 18 years or older. 2. Chronically HIV-infected patients stable on ART of 2 NRTI + PI/r (VL <50cps/ml for >6 months) 3. Subjects who fulfil the criteria for replacement of their current antiretroviral therapy according to section 3.4 in the “Deutsch-Österreichische Leitlinien zur antiretroviralen Therapie der HIV-1-Infektion” (DAIG, Mar 2010) 4. Documented CCR5-tropism at baseline (proviral DNA) 5. Written informed consent signed prior to study entry
|
|
E.4 | Principal exclusion criteria |
1. Documented positive X4-tropism lab result in the history 2. Documented relevant genotypic resistance mutations to current PI/r 3. Contraindications to Maraviroc (i.e. hypersensitivity to maraviroc, peanuts, soy beans) 4. Previous treatment with Maraviroc 5. Evidence of drug intolerability 6. Liver Function Tests (LFT) > 5x upper limit of normal 7. History of any serious medical condition, which in the opinion of the investigator, would compromise the safety of the subject 8. Active Cancer 9. Participation in any other investigational drug trial 10. Chronic Hepatitis B, since it may be treated by TDF or 3TC in the backbone regime 11. Diabetes mellitus type II 12. Subject is enrolled in one or more investigational drug/vaccine protocols (30 days prior to Screening) 13. Satisfies any contraindications or restrictions to ABC therapy as listed in the product labels. Treatment with ABC must be in line with the recommendations of the product label. 14. Subjects who are institutionalized or prison inmates |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Difference in change from baseline in mtDNA/nucDNA ratio (cps/cell) in PBMC and urinary sediment cells at week 48 between groups. 2. Difference in proportion of CD4+CD38+ and CD8+CD38+ cells at week 48 between groups.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Difference in change from baseline in mtDNA/nucDNA ratio (cps/cell) in PBMC and urinary sediment cells at week 48 between groups • Difference in change from baseline in cytochrome c oxidase (COX) enzyme activity ratio in urinary sediment cells at week 48 between groups • Difference in proportion of CD4+CD38+DR+ and CD8+CD38+DR+ cells at week 24 between groups • Difference in change from baseline in IL-6, hsCRP, MPO and Anti-PCs at week 24 and 48 between groups • Difference in change from baseline in fractional phosphate excretion at week 24 and 48 between groups • Difference in proportion of patients with VL <50cps/ml at week 24 and 48 (ITT TLOVR) • Difference in absolute change from baseline in CD4 cell count at week 24 and 48 between groups • Difference in absolute change from baseline in lipid parameters (LDL, HDL, TC, TC:HDL, TC, TG) at week 24 and 48 between groups • Rate of Grade 2-4 adverse events and laboratory abnormalities |
|
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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 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 | 5 |
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 | 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
|
Last visit of the last subject |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |