E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonalcoholic Steatohepatitis with fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
Fatty Liver where the cells in the liver have abnormal fat built-up and built-up of scar tissue in the liver. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053219 |
E.1.2 | Term | Non-alcoholic steatohepatitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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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 |
Hepatic histological improvement in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) at Year 1 relative to Screening biopsy, defined by a minimum 2-point improvement in NAS with at least a 1-point improvement in more than 1 category and with no concurrent worsening of fibrosis stage (worsening defined as progression to bridging fibrosis or cirrhosis) |
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E.2.2 | Secondary objectives of the trial |
Evaluate the resolution of NASH with no concurrent worsening of fibrosis stage (worsening defined as progression to bridging fibrosis or cirrhosis) at Year 2 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
--Histological evidence of NASH, based on Screening biopsy, with a NAS of ≥ 4 with at least 1 in each component of NAS --Histological evidence of liver fibrosis defined as NASH CRN System Stage 1 to 3, inclusive, based on Screening biopsy --Meeting any of the 3 following major criteria (a, b, c): a. Documented evidence of type 2 diabetes mellitus (T2DM) b. High BMI (> 25 kg/m2) with at least 1 of the following criteria of the metabolic syndrome, as defined by the NCEP: i. Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches (female) ii. Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dL) iii. Dyslipidemia: HDL-cholesterol < 40 mg/dL (male), < 50 mg/dL (female) iv. Blood pressure ≥ 130/85 mmHg (or treated for hypertension) v. Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dL) c. Bridging fibrosis (NASH CRN Stage 3) and/or definite NASH (NAS ≥ 5) --Agree to have one liver biopsy at Screening, one at Year 1, and one at the end of study treatment (Year 2)
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E.4 | Principal exclusion criteria |
--Hepatitis B surface antigen (HBsAg) positive --Hepatitis C antibody (HCVAb) positive with the following 2 exceptions: a. Subjects previously treated for viral hepatitis C with at least a 1-year period since documented sustained virologic response at Week 12 (post-treatment) may be eligible if all other eligibility criteria are met b. Subjects with presence of hepatitis C antibody but negative hepatitis C virus RNA without treatment (i.e., spontaneous clearance) may be eligible if all other eligibility criteria are met --Prior or planned liver transplantation --Other known causes of chronic liver disease, including alcoholic liver disease --History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding --Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is ½ pint of beer [285 mL], 1 glass of spirits [25 mL] or 1 glass of wine [125 mL]) -HIV-1 and HIV-2 infection due to CVC's anti-HIV activity |
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E.5 End points |
E.5.1 | Primary end point(s) |
Hepatic histological improvement in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) at Year 1 relative to Screening biopsy, defined by a minimum 2-point improvement in NAS with at least a 1-point improvement in more than 1 category and with no concurrent worsening of fibrosis stage (worsening defined as progression to bridging fibrosis or cirrhosis) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Biopsies will be performed at Screening, Year 1, and Year 2 |
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E.5.2 | Secondary end point(s) |
Resolution of NASH with no concurrent worsening of fibrosis stage (worsening defined as progression to bridging fibrosis or cirrhosis) at Year 2 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments will be performed every three months for two years. |
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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 | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Moldova, Republic of |
Poland |
Romania |
Spain |
United Kingdom |
United States |
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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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LPLV- Last patient last visit |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |