E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
To investigate changes from week 12 to week 36 in levels of inflammation within the fluid that surrounds the Central Nervous System, called cerebrospinal fluid or CSF, when maraviroc is taken along with regular darunavir/ritonavir monotherapy for 24 weeks.
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E.2.2 | Secondary objectives of the trial |
To investigate change from baseline to week 12 in levels of inflammation in CSF on darunavir/ritonavir monotherapy (control phase).
To investigate the occurrence of viral load level blips (short term changes) whilst on darunavir/ritonavir plus maraviroc.
To investigate changes in CD4 count (marker of immune system).
To investigate changes in neurocognitive function (brain functioning).
To assess the safety and tolerability of darunavir/ritonavir plus maraviroc.
To look at MRI brain changes over the course of the study.
To examine drug levels of darunavir, maraviroc and ritonavir in CSF. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- male or female aged 18 years or above. - has a documented HIV-1 infection. - has signed the Informed Consent Form voluntarily. - is willing to comply with the protocol requirements. - has an HIV-plasma viral load at screening <40 copies/mL (one off retesting for blips <200 copies/ml is allowed). - has a CD4 cell count at Screening >50 cells/mm3. - has been on a stable DRV/r alone for at least 12 weeks at Screening, and willing to remain on this. - estimated glomerular filtration rate (by MDRD or CG methods) >50 ml/min at screening. - CCR5 tropic by geno2pheno assay performed at screening. - if female and of childbearing potential, she is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial (or after last intake of investigational ARVs). Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential. - if a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit. |
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E.4 | Principal exclusion criteria |
- is infected with HIV-2. - is using any concomitant therapy disallowed as per SPC for the study drugs. - has a currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions (must be discussed with the Investigator prior to enrolment). - Stable cutaneous Kaposi’s Sarcoma (no pulmonary or gastrointestinal involvement other than oral lesions) unlikely to require systemic therapy during the trial period. - CD4 count less than 200 cells/mm3. Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed. - has acute viral hepatitis including, but not limited to, A, B, or C. - has chronic hepatitis B and/or C. - has received any investigational drug within 30 days prior to the trial drug administration. - Clinically significant allergy or hypersensitivity to any trial medication excipients. - If female, she is pregnant or breastfeeding. - Screening blood results with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed). - Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR > 1.5 or albumin < 30g/L or bilirubin > 2.5 x ULN. - Platelets of < 50 based on lumbar puncture examination at baseline. - Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from week 12 to week 36 in inflammatory markers in CSF when maraviroc (150mg qd) is added to stable darunavir/ritonavir (800/100mg qd) monotherapy for 24 weeks. |
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E.5.2 | Secondary end point(s) |
Change from baseline to week 12 in CSF inflammatory markers on darunavir/ritonavir monotherapy (control phase).
Frequency of viral load blips whilst on darunavir/ritonavir plus maraviroc.
Changes in CD4 count from baseline to week 12 and week 12 to week 36.
Changes from control phase (baseline-week12) and week 36 in neurocognitive scores.
Proportion of subjects experiencing grade 2-4 clinical adverse events (at least possibly drug-related) at baseline, week 12, week 16 and week 36.
Proportion of subjects experiencing grade 2-4 laboratory abnormalities at baseline, week 12, week 16 and week 36.
Changes in MRI brain scanning over 36 weeks.
Drug concentrations of darunavir, ritonavir and maraviroc at week 36 in CSF (compared to matched plasma samples calculated as plasma:CSF ratio) |
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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 | 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 | Yes |
E.8.1.3 | Single blind | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Darunavir/Ritonavir alone (0-12weeks) against Darunavir/Ritonavir plus Maraviroc (week12-36) |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |