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. MedDRA versio
Conditions
Interventions
Trade Name: Celcentri
Product Name: Celcentri
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MARAVIROC
CAS Number: 376348-65-1
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
mib Dienstleistungsgesellschaft mbH
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Effect of Switching from NRTIs to Maraviroc on markers of mitochondrial toxicity - Effect of Switching from NRTIs to Maraviroc on markers of immune activation ;Secondary Objective: - 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;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. ;Timepoint(s) of evaluation of this end point: Baseline, Week48 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;Timepoint(s) of evaluation of this end point: Baseline, Week24, week48 | — |
Countries
Germany
Contacts
Public ContactSponsor
mib Dienstleistungsgesellschaft mbH
Outcome results
None listed