| Outcome Measures: |
Main Objective: To evaluate the efficacy on steatosis reduction as measured by NMRS of two Aramchol doses (400 mg and 600 mg), once daily for 52 weeks vs placebo. ;<br> Secondary Objective: 1. To evaluate the efficacy of Aramchol on CRN Fibrosis Score by liver biopsy.<br> 2. To evaluate the efficacy of Aramchol on disease activity as measured by NAS and SAF activity score<br> 3. To evaluate the efficacy of Aramchol on NASH resolution by liver biopsy.<br> 4. To evaluate the effect of Aramchol on ALT levels.<br> Exploratory objectives:<br> 1. To evaluate the effect of Aramchol on metabolic parameters.<br> 2. To compare two doses in order to choose the optimal dose for pivotal Phase III studies.<br> 3. To assess Aramchol?€?s effect on NASH activity by non-invasive diagnostic methods.<br> 4. To validate new non-invasive tests for the diagnostic and assessments of Aramchol?€?s effect.<br> 5. To conduct blood trough level of Aramchol.<br> ;Primary end point(s): Percent (%) change from baseline to end of study in liver triglycerides ratio as measured by NMRS.;Timepoint(s) of evaluation of this end point: At screening and at week 52<br> Secondary end point(s): 1. Proportion (%) of subjects with CRN fibrosis score improvement<br> 2. Proportion (%) of subjects with NAS score improvement without worsening of CRN fibrosis score.<br> 3. Proportion (%) of subjects with SAF activity score improvement without worsening of CRN Fibrosis Score.<br> 4. Proportion (%) of subjects with NASH resolution without worsening of CRN fibrosis score<br> 5. Change from baseline to Week 52/Termination in ALT (U/L) levels.<br> Exploratory endpoints:<br> 1. Change from baseline to Week 52/Termination in HOMA-IR (UNITS).<br> 2. Change from baseline to Week 52/Termination in HEMOGLOBIN A1C (%).<br> 3. Change from baseline to Week 52/Termination in<br> ADIOPONECITINE (TOTAL) (mg/L).<br> 4. Change from baseline to Week 52/Termination in LEPATIN (pg/mL) / ADIOPONECITINE (TOTAL) (mg/L) ratio (LAR)<br> 5. Change from baseline to Week 52/Termination in inflammation and fibrosis biomarkers: FIBRINOGEN (ACT) (g/L), CYTOKERATIN 18 (M-30) (U/L), CYTOKERATIN 18 (M-65) (U/L), hs-CRP (mg/L), HS-IL6 (ng/L), TNFa [HS-TNF A (ng/L)] and NAFLD fibrosis score (NFS).<br> 6. Change from baseline to Week 52/Termination in body weight and in waist circumference.<br> 7. Change from baseline to Week 52/Termination in fatty liver index (FLI).<br> 8. Endothelial function.<br> 9. Aramchol blood trough level.<br> 10. Metabolomics.<br> 11. Genetic profiling.<br> ;<br> Timepoint(s) of evaluation of this end point: 1. At screening and at week 52.<br> 2. At screening and at week 52.<br> 3.At screening, baseline, visit 2, visit 7, visit 10, visit 11.<br> 4. At screening, week 24, week 52, and unscheduled visit.<br> 5. At screening, week 8, week 24, week 40, week 52, and unscheduled visit.<br> 6. At screening and at week 52.<br> 7. At screening and at week 52.<br> 8. At screening, baseline, week 24, week 52, week 65, and unscheduled visit.<br>
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