Obese Patients With Non-alcoholic Steatohepatitis (NASH) Clinical Trial
Official title:
A 12-week Randomized, Patient and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate the Efficacy of LIK066 in Obese Patients With Non-alcoholic Steatohepatitis (NASH)
| Verified date | October 2021 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study was to assess the effects of LIK066 on a variety of metabolic and inflammation biomarkers in patients with non-alcoholic steatohepatitis (NASH)
| Status | Completed |
| Enrollment | 107 |
| Est. completion date | November 14, 2019 |
| Est. primary completion date | November 11, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: EITHER -Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3 in the absence of a histological diagnosis of alternative chronic liver disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening. OR Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening: - ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND - BMI greater than or equal to 27 kg/m^2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m^2 (in patients with a self identified Asian race) AND - Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10% - Patients must weigh no more than 150 kg (330 lbs) to participate in the study. - Male and female patients 18 years or older at the time of screening visit. Exclusion Criteria: - History or presence of other concomitant liver diseases - History or current diagnosis of ECG abnormalities - Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study - Patients with contraindications to MRI imaging - Current or history of significant alcohol consumption - Clinical evidence of hepatic decompensation or severe liver impairment - Women of child bearing potential (unless on basic contraception methods) - Presence of liver cirrhosis |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Novartis Investigative Site | Buenos Aires | |
| Argentina | Novartis Investigative Site | Caba | Buenos Aires |
| Canada | Novartis Investigative Site | Montreal | Quebec |
| Israel | Novartis Investigative Site | Haifa | |
| Israel | Novartis Investigative Site | Ramat Gan | |
| Israel | Novartis Investigative Site | Tel Aviv | |
| Netherlands | Novartis Investigative Site | Leiden | |
| Russian Federation | Novartis Investigative Site | St-Petersburg | |
| Taiwan | Novartis Investigative Site | Chia-Yi | |
| Taiwan | Novartis Investigative Site | Tainan | |
| Thailand | Novartis Investigative Site | Bangkok | |
| United States | Novartis Investigative Site | Baton Rouge | Louisiana |
| United States | Novartis Investigative Site | Knoxville | Tennessee |
| United States | Novartis Investigative Site | Live Oak | Texas |
| United States | Novartis Investigative Site | Saint Louis | Missouri |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Argentina, Canada, Israel, Netherlands, Russian Federation, Taiwan, Thailand,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 | Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits. | Baseline, Week 12 | |
| Secondary | Change From Baseline in Percent Liver Fat at Week 12 | Percent (%) Liver fat was measured by Magnetic Resonance Imaging Proton Density Liver Fat Fraction(MRIPDFF). Patients underwent magnetic resonance imaging twice during the course of the study ( baseline and end of treatment) to quantitate liver fat. | Baseline, Week 12 | |
| Secondary | Percent Change From Baseline in Total Body Weight at Week 12 | Body weight (to the nearest 0.1 kilogram [kg] was measured on a calibrated scale. The measurement was performed with the study subject in underwear and without shoes; or while wearing minimal indoor clothing. | Baseline, Week 12 | |
| Secondary | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12 | The markers of fibrosis assessed in this test comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during fibrogenesis as a result of activation of the hepatic stellate cell. The ELF test is a composite score: < 7.7: no to mild fibrosis; = 7.7 - < 9.8: Moderate fibrosis; = 9.8 - < 11.3: Severe fibrosis; = 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis. | Baseline, Week 12 | |
| Secondary | Change From Baseline in the Concentration of Hyaluronic Acid at Week 12. | Hyaluronic Acid is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). | Baseline, Week 12 | |
| Secondary | Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12. | PIIINP is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). | Baseline, Week 12 | |
| Secondary | Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12. | TIMP-1 is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). | Baseline, Week 12 | |
| Secondary | Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration | Cmax is the observed maximum plasma concentration following drug administration (ng/mL) | Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose) | |
| Secondary | Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration | Tmax is the time to reach the maximum concentration after drug administration (hour). The time points presented are the actual and not the planned time points. | Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose) | |
| Secondary | Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration | AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (hour*ng/mL) | Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose) | |
| Secondary | Change From Baseline in Aspartate Aminotransferase (AST) at Week 12 | Aspartate aminotransferase (AST) is an enzyme found in many cells of the body specifically those of the liver, heart and skeletal muscle. In healthy individuals, levels of AST in the blood are low. When liver or muscle cells are injured, they release AST into the blood. In this study, the blood levels of AST was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits. | Baseline, Week 12 |