Non alcoholic steatohepatitis (NASH) in patients with HIV mono-infection
Conditions
Interventions
Trade Name: Celsentri 150mg
Product Name: Celsentri
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MARAVIROC
CAS Number: 376348-65-1
Current Sponsor code: ViiV Healthcare
Concentration u
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. HIV-1 infected individuals (males and females) aged 18-75 years 2. Stable antiretroviral therapy for at least one year on a regimen that is unlikely to change in the next 12 months. 3. At least two consecutive undetectable HIV viral loads defined by HIV RNA =50 copies/mm3 for = 6 months from the date of inclusion. 4. CD4 count = 200 cells/mm3 5. Histological evidence of NASH based on liver histology performed within 12 months prior to enrollment with a NAFLD activity score (NAS) = 4 with a score of at least 1 in each component (steatosis, lobular inflammation, and hepatocyte ballooning)[19] and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Liver co-morbidities: 1. Positive HBs antigen (HBsAg) 2. Positive HCV antibody (HCVAb), with the exception of subjects with the presence of HCVAb but negative hepatitis C virus RNA without treatment (i.e. spontaneous clearance following acute infection). 3. Underlying acute or chronic liver disease including non- B non- C viral hepatitis (A & E), autoimmune liver disease, biliary disease, hemochromatosis, Wilson´s disease, alpha-1-antitrypsin deficiency. 4. History of decompensated cirrhosis including ascites, hepatic encephalopathy, or variceal bleeding. 5. Suspicion of drug-related toxicity defined by abnormal LFTs following the recent introduction of a new medication. 2) Additional co-morbidities: 1. Active, serious infections that require parenteral antibiotic or antifungal therapy within 30 days prior to screening visit. 2. Active AIDS-defining disease other than oesophageal candidiasis. 3. Any active life- threatening disease Full Set of Project Data IRAS Version 5.5.1 12 DRAFT4. Active malignancy (except for early dysplastic lesions eg anal dysplasia) 5. Congestive cardiac failure 6. Platelet count 1.4 7. Severe renal impairment with CrCl<30mL/min 3) Lifestyle: 1. Excessive alcohol consumption during the last 6 months prior inclusion defined by more than 14 units/week for women or 21 units/week for men 4) Concomitant medications: 1. Patients actively treated with Maraviroc or having received Maraviroc over the last 12 months. 2. Weight reduction through bariatric surgery in the past 5 years or planned during the conduct of the study. 3. Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents or immunomodulating agents. 4. Receiving any experimental medications within 30 days prior to screening or anticipated use during the trial. 5. Patients receiving pioglitazone, rosiglitazone, vitamin E 800 IU/day, , and/or ursodeoxycholic acid since these drugs may have confounding effect on efficacy of MVC 5) Others 1. Females who are pregnant or breastfeeding 2. Allergy to the study drug or its components (including peanut and soya) 3. Participation in any other clinical trial at Screening without approval from the Sponso
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: A change in hepatic immune cells- including CD3+, CD4+, CD8+, T-bet+, CD56, CD68, CD163 and myeloperoxidase positive cells identified on liver biopsy tissue using immunohistochemistry- following 48 weeks MVC ;Secondary Objective: 1. Improvement in biochemical (fasting glucose, lipids and HOMA index) metabolic parameters at EOT as compared to baseline. 2. Modification of circulating inflammatory cytokines, adipokines and markers of macrophage activation (high sensitive IL6, sTNFR1 /2, sCD14, sCD163, hsCRP, Leptin, Total and High molecular weight adiponectin) at EOT as compared to baseline. 3. Number of subjects with a reduction in the NAS score by =2 points without worsening of fibrosis at EOT as compared to baseline. 4. Number of subjects with a reduction in the degree of liver steatosis, inflammation and/or ballooning at EOT as compared to baseline 5. Number of subjects with a reduction of at least one stage of liver fibrosis in patients with fibrosis at EOT as compared to baseline 6. Number of subjects with a reduction of Fibroscan® values and biochemical markers of fibrosis (APRI, Fib-4, NAFLD Fibrosis Score[5]) from at EOT as compared to baseline ;Primary end point(s): A change in hepatic immune cells- including CD3+, CD4+, CD8+, T-bet+, CD56, CD68, CD163 and myeloperoxidase positive cells identified on liver biopsy tissue using immunohistochemistry- following 48 weeks MVC therapy.;Timepoint(s) of evaluation of this end point: Compare values at baseline (within 12 months before enrollment) with values after 48 weeks treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Improvement in biochemical (fasting glucose, lipids and HOMA index) metabolic parameters at EOT as compared to baseline. 2. Modification of circulating inflammatory cytokines, adipokines and markers of macrophage activation (high sensitive IL6, sTNFR1 /2, sCD14, sCD163, hsCRP, Leptin, Total and High molecular weight adiponectin) at EOT as compared to baseline. 3. Number of subjects with a reduction in the NAS score by =2 points without worsening of fibrosis at EOT as compared to baseline. 4. Number of subjects with a reduction in the degree of liver steatosis, inflammation and/or ballooning at EOT as compared to baseline 5. Number of subjects with a reduction of at least one stage of liver fibrosis in patients with fibrosis at EOT as compared to baseline 6. Number of subjects with a reduction of Fibroscan® values and biochemical markers of fibrosis (APRI, Fib-4, NAFLD Fibrosis Score[5]) from at EOT as compared to baseline 7. Number of subjects with normalization of Fibroscan values at the EOT 8. Number of subjects with a reduction in liver transaminases (ALT and AST) levels during the course and the EOT 9. Additional stool and urine samples will be collected at baseline and EOT and stored in Imperial College Gastroenterology and Hepatology Biobank for analysis of the impact of the intestinal microbiome and associated metabolic biomarkers on the progression of NAFLD/NASH in HIV;Timepoint(s) of evaluation of this end point: Compare values at baseline with values after 48 weeks treatment | — |
Countries
Germany, United Kingdom
Contacts
Public ContactMaud Lemoine
Imperial College
Outcome results
None listed