Health Condition 1: K758- Other specified inflammatory liverdiseases
Conditions
Interventions
Intervention1: Resmetirom 80 mg oral tablets: Orally, once a day for 52 Weeks
Intervention2: Resmetirom 100 mg oral tablets: Orally, once a day for 52 Weeks
Intervention3: Resmetirom 80 mg Tablets: Or
Sponsors
Torrent Pharmaceuticals Ltd, Torrent Research Centre
Torrent Pharmaceuticals Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female between 18-70 (both inclusive) years of age, at the time of signing informed consent. 2. Diagnosis of NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) confirmed by liver biopsy, with non-alcoholic fatty liver disease (NAFLD) activity score [NAS] greater than or equal to 4, with at least 1 point in steatosis, ballooning degeneration, and lobular inflammation each, conducted during the screening period or by a historical biopsy conducted within 6 months prior to screening. 3. Subjects receiving antidiabetic, antihypertensive, lipid modifying medication(s) as background therapy should be on a stable dose for at least 3 months before screening. 4. Subject is willing to provide written informed consent document and have ability and willingness to adhere to the protocol.
Exclusion criteria
Exclusion criteria: 1. Subjects with history of alcohol consumption of greater than 30 gm/day for men, greater than 20 gm/day for women for 3 consecutive months in the last 2 years. 2. History or presence of cirrhosis at screening. 3. Any current or prior history of decompensated liver disease including ascites requiring medical management, hepatic encephalopathy (HE), or variceal bleeding. 4. History or presence of concomitant liver diseases other than NASH at screening. 5. History of liver transplantation or hepatocellular carcinoma (HCC). 6. Subjects receiving predefined prohibited drugs within 24 weeks prior to screening. 7. Subjects with thyroid diseases either hyperthyroidism or hypothyroidism. 8. Significant (more than 5%) weight gain or loss in 12 weeks prior to screening. 9. Any weight reduction surgery in the 2 years prior to screening or planned during the study period. 10. Subjects with history of major or minor surgery or invasive procedure within 24 weeks prior to screening. 11.Subjects with any planned major or minor surgery or invasive procedure within the next 56 weeks from the day of screening. 12. Subjects suffering from Type 1 diabetes. 13. Subjects with Type 2 diabetes with poor glucose control [defined as glycated haemoglobin (HbA1C) greater than or equal to 9.5% within 12 weeks] or subjects who required to take insulin treatment within 12 weeks prior to screening. 14. Subjects with any of the following laboratory values at screening: Platelets less than 140000/ L International normalised ratio (INR) greater than 1.4 (in the absence of anticoagulants) Direct bilirubin greater than 0.3 mg/dL. Total bilirubin greater than 1.5x ULN Serum albumin less than 3.5 g/dL (35.0 g/L) Estimated Glomerular Filtration Rate (eGFR) less than 45 ml/min/1.73 m2 ALP greater than or equal to 2x ULN AST {serum glutamic oxaloacetic transaminase (SGOT)}, ALT {serum glutamic pyruvic transaminase (SGPT)} greater than or equal to 5x ULN 15. History or presence of cholelithiasis, acute cholecystitis, and obstructive pancreatitis (gallstone). 16. History of anaemia or hemoglobinopathy and or hemoglobin less than 10 g/dL for men, hemoglobin less than 9 g/dL for women at screening. 17. Subjects with any of the following: myocardial infarction, stroke or unstable angina and/or transient ischaemic attack within 24 weeks prior to screening. 18. Subjects with New York Heart Association (NYHA) Class III or IV heart failure. 19. Poorly controlled hypertension (systolic blood pressure greater than 160 mm Hg, or diastolic blood pressure greater than 100 mm Hg) at the screening visit. 20. Subject with history or presence of human immunodeficiency viruses (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). 21. Subject with history or presence of malignant neoplasms within the last 5 years or currently receiving any anticancer medication. 22. Known allergy, sensitivity or intolerance to the study drug. 23. Subjects had been participated in any clinical trials for NASH within 24 weeks prior to the screening or had been participated in any other investigational drug clinical trial within 12 weeks prior to the screening. 24. Female who is pregnant, breast-feeding or intends to become pregnant or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects with NASH resolution with no worsening of fibrosisTimepoint: 52 Week | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with at least a 1-point improvement in fibrosis stage with no worsening of steatohepatitisTimepoint: 52 Week;Mean change in NAS score from baselineTimepoint: 52 Week;Mean change in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) from baselineTimepoint: 24 week & 52 Week;Proportion of subjects achieving ALT normalizationTimepoint: 24 Week & 52 Week;Mean change in fasting lipid profile [total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, high density lipoproteins (HDL) cholesterol, triglycerides (TG)] from baselineTimepoint: 24 Week & 52 Week;Change in non-invasive biomarkers of fibrosis like AST-to-Platelet Ratio Index (APRI), NAFLD fibrosis score (NFS), fibrosis-4 (FIB4), BARD score from baselineTimepoint: 52 Week;Number of treatment emergent adverse events (TEAEs).Timepoint: Throughout the Study | — |
Countries
India
Contacts
Public ContactDr Prashant Jamadarkhana
Torrent Pharmaceuticals Limited Torrent Research Centre
Outcome results
None listed