E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic fatty liver disease in people living with well-controlled HIV-1 infection |
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E.1.1.1 | Medical condition in easily understood language |
A disease of too much fat laid down in the liver in people who have HIV and do not drink over the recommended limit of alcohol |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029530 |
E.1.2 | Term | Non-alcoholic fatty liver |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008919 |
E.1.2 | Term | Chronic HIV infection |
E.1.2 | System Organ Class | 100000004862 |
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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 principal objective is to assess how feasible and acceptable it will be to add in maraviroc to a person's anti-HIV medications as a possible treatment for non-alcoholic fatty liver disease |
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E.2.2 | Secondary objectives of the trial |
The secondary research questions are:
Does taking the anti-HIV drug maraviroc improve liver disease in people who have HIV and the condition non-alcoholic fatty liver disease over a 1 and 2 year period?
This will be measured by 1. bloods tests (measuring the degree of liver scarring, markers of fats in the blood, a diabetes blood test, and liver enzymes or chemicals released by the liver) 2. scans (Fibroscans, which measure liver scarring).
Does the quality of life for people with HIV and NAFLD change if they take maraviroc compared to those who don't take maraviroc over a 1 and 2 year period? This will be measured by completion of questionnaires. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
(1) Aged 18 years and older
(2) HIV-1 infected with durably suppressed (≥ 6 months) HIV VL
NB. One HIV VL blip is allowed in the 6 months prior to screen.
(3) Has had ≤ 6 months prior exposure to maraviroc
(4) Has evidence of NAFLD on hepatic imaging (USS, CT or MRI) either at screen or in the 6 months prior to screen
(5) Provides written, informed consent to participate
(6) Is willing to comply with the protocol requirements
(7) If female and of child bearing potential, is using effective birth control methods (as agreed by the investigator) and willing to continue practising these birth control measures during the trial and for at least 30 days after the end of the trial. Note: Women who are postmenopausal for least 2 years, women with a total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential
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E.4 | Principal exclusion criteria |
Exclusion criteria
(1) Severe cardiovascular disease including known angina or history of myocardial infarction
(2) History of postural hypotension, defined as a reduction in the systolic blood pressure of ≥ 20mmHg after standing for at least one minute
(3) Individuals already receiving MVC at screening
(4) HIV viral load detectable (one blip within 6 months prior to screen is allowed)
(5) Current HCV or HBV (HBcAb-positive, HBsAg-negative is permitted; anti-HCV Ab positive with HCV RNA negative for ≥ 12 months following treatment or spontaneous clearance is permitted)
(6) Other chronic liver disease including but not exclusively: cirrhosis, alcohol-related liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, haemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, non-cirrhotic portal hypertension, drug-induced as deemed by a hepatologist
(7) ALT or AST > 3x the ULN (where ULN is defined locally as 41 IU/L)
(8) Severe renal insufficiency (creatinine clearance < 30 mL/min)
(10) HIV-2 infection
(11) Known allergy or intolerance to MVC or its constituents including hypersensitivity to peanuts or soya
(12) If female, pregnancy or breastfeeding
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E.5 End points |
E.5.1 | Primary end point(s) |
Feasibility and acceptability of addition of maraviroc to optimised background therapy in patients with HIV-1 infection and non-alcoholic fatty liver disease. This will be assessed by the following:
a) Acceptability of recruitment into the study to eligible individuals b) Monthly participant recruitment rate c) Participant retention rate d) Completeness of the data set e) Proportion of individuals reporting adverse events f) Self-reported adherence to the study drug
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and weeks 48 and 96 |
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E.5.2 | Secondary end point(s) |
The secondary outcome measures will be:
Assessment of the effect of addition of maraviroc to optimised background therapy (OBT), versus continuing OBT alone, on non-invasive markers of hepatic fibrosis in people living with HIV and NAFLD. These markers will be changes in the ELF blood test, Fibroscan, diabetes test, lipid tests, liver enzyme tests.
Assessment of the effect of addition of maraviroc to optimised background therapy (OBT), versus continuing OBT alone, on quality of life in people living with HIV and NAFLD. This will be measured by three questionnaires. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and weeks 48 and 96
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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 | 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 |
Feasibility and acceptability |
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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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 2 |
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 | 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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |