Nonalcoholic Steatohepatitis
Conditions
Brief summary
The purpose of this study is to determine whether cenicriviroc is effective and safe in the treatment of nonalcoholic steatohepatitis (NASH) in adult participants with liver fibrosis.
Interventions
DRUGCenicriviroc
CVC 150 mg, administered orally once daily and taken every morning with food.
DRUGPlacebo
Placebo administered orally once daily and taken every morning with food.
Sponsors
Tobira Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult participants aged between 18-75 * Histological evidence of NASH, based on biopsy, with a Nonalcoholic fatty liver disease Activity Score (NAS) of \>= 4 with at least 1 in each component of NAS * Histological evidence of liver fibrosis defined as NASH Clinical Research Network (CRN) System Stage 1 to 3 * Meeting any of the 3 major criteria (a, b, c): 1. Documented evidence of type 2 diabetes mellitus 2. High body mass index (\> 25 kg/m\^2) with at least one of the following criteria of metabolic syndrome, as defined by the National Cholesterol Education Program: * Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches (female) * Dyslipidemia: Triglycerides ≥ 1.7 mmol/L (150 mg/dL) * Dyslipidemia: High-density lipoprotein (HDL)-cholesterol \< 40 mg/dL (male), \< 50 mg/dL (female) * Blood pressure ≥ 130/85 mmHg (or currently being treated for hypertension) * Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dL) 3. 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) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal (ULN)
Exclusion criteria
* Hepatitis B surface Antigen (HBsAg) positive * Hepatitis C antibody (HCVAb) positive with the following 2 exceptions: 1. Participants 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 2. Participants with presence of hepatitis C antibody but negative hepatitis C virus ribonucleic acid 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 \[125 mL\]) * Human immunodeficiency virus (HIV)-1 or HIV-2 infection * Weight reduction through bariatric surgery in the past 5 years or planned during the conduct of the study (including gastric banding) * Females who are pregnant or breastfeeding * Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with the dosing and protocol requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant With Hepatic Histological Improvement in NAS by ≥ 2 Points With at Least 1-Point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and no Concurrent Worsening of Fibrosis at Year 1 | Year 1 | Hepatic histological improvement in Nonalcoholic Fatty Liver Disease Activity Score (NAS) at Year 1 was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Evaluation of fibrosis stage was based on the nonalcoholic steatohepatitis clinical research network (NASH CRN) fibrosis staging system, which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. Worsening of fibrosis stage was defined as progression of NASH CRN fibrosis stage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2 | Year 2 | Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. |
| Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1 | Year 1 | Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. |
| Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2 | Year 2 | Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. |
| Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1 | Year 1 | The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. |
| Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2 | Year 2 | The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. |
| Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | Years 1 and 2 | A TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 30 days after the discontinuation of the study medication. An SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life threatening, requires hospitalization or results in prolongation of existing hospitalization, results in disability/incapacity, or was a congenital anomaly/birth defect. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Years 1 and 2 | Vital signs included blood pressure, temperature, heart rate, and respiration rate. Vital signs were reviewed by the Investigator for clinically significant changes. |
| Number of Participants With Clinical Laboratory Abnormalities | Years 1 and 2 | Grade 3-4 abnormal clinical laboratory values that occurred in ≥2% participants were reported. Criteria used for various parameters was:Fasting glucose Grade3:\>250 - 500 mg/dL and Grade4: \>500 mg/dL; Alanine aminotransferase(ALT)Grade3:\>5.0 - 20.0 ×Upper Limit of Normal(ULN)and Grade4:\>20.0 ×ULN; Aspartate aminotransferase(AST)Grade3: \>5.0 - 20.0 ×ULN and Grade4: \>20.0 ×ULN; Activated partial thromboplastin(APT)/Partial thromboplastin time(PTT)Grade3: \>2.5×ULN; Triglycerides Grade3 \>500 - 1000 mg/dL and Grade4: \>1000 mg/dL; Gamma-glutamyl transferase(GGT)Grade3: \>5.0 - 20.0 ×ULN and Grade4: \>20.0 ×ULN; Creatine kinase Grade 3: \>5.0 - 10.0 ×ULN and Grade4: \>10.0 ×ULN; Uric acid Grade3:(ULN - 10 mg/dL; ULN - 0.59 mmol/L) and Grade4: \>10 mg/dL; Amylase Grade3: \>2.0 - 5.0 ×ULN and Grade4: \>5.0 ×ULN; Lipase Grade3: \>2.0 - 5.0 xULN and Grade4: \>5.0 xULN; Phosphorus Grade3: \<2.0 - 1.0 mg/dL and Grade4: \<1.0 mg/dL and Absolute neutrophil Grade3: \<1.0 - 0.5 × 109/L and Grade4: \<0.5 × 109/L. |
| Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings | Years 1 and 2 | A 12-lead ECG was performed. ECG results were reviewed by the Investigator for clinically notable abnormalities. |
| Number of Participants With Hepatic Histological Improvement in NAS at Year 2 | Year 2 | Hepatic histological improvement in NAS at Year 2 was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. |
| Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Year 1 | NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= \<5%, 1= 5 - 33%, 2= \>33 - 66%, and 3= \>66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= \< 2 foci/200x, 2= 2-4 foci/200x, and 3= \> 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement. |
| Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Year 2 | NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= \<5%, 1= 5 - 33%, 2= \>33 - 66%, and 3= \>66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= \< 2 foci/200x, 2= 2-4 foci/200x, and 3= \> 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement. |
| Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-Point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1 | Year 1 | Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either steatosis, lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Worsening was defined as progression of NASH CRN fibrosis stage. |
| Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2 | Year 2 | Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either steatosis, lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Worsening was defined as progression of NASH CRN fibrosis stage. |
| Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1 | Year 1 | Resolution of NASH was defined as having no hepatocellular ballooning (grade 0) and minimal to no lobular inflammation (grade 1 or 0) with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH CRN fibrosis stage). |
| Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2 | Year 2 | Resolution of NASH was defined as having no hepatocellular ballooning (grade 0) and minimal to no lobular inflammation (grade 1 or 0) with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH CRN fibrosis stage). |
| Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1 | Year 1 | The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 1. A negative change from Baseline indicates improvement. |
| Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2 | Year 2 | The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 2. A negative change from Baseline indicates improvement. |
| Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1 | Baseline (Day 1) to Year 1 | The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 1. A positive change from Baseline indicates worsening. |
| Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 | Baseline (Day 1) to Year 2 | The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 2. A positive change from Baseline indicates worsening. |
| Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1 | Year 1 | The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 1. A negative change from Baseline indicates improvement. |
| Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2 | Year 2 | The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 2. A negative change from Baseline indicates improvement. |
| Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Baseline (Day 1) to Year 1 | The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A positive change from Baseline indicates worsening. |
| Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Baseline (Day 1) to Year 2 | The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A negative change from Baseline indicates improvement. |
| Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 | Baseline (Day 1) to Year 1 | Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening. |
| Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 | Baseline (Day 1) to Year 2 | Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening. |
| Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Baseline (Month 0) to Months 3, 6 and 12 | APRI is the ratio of aspartate aminotransferase (AST) to platelet count. It is calculated using formula, APRI = (AST level \[/ULN\] / platelet counts \[10\^9/L\]) \* 100. An APRI index of \<=0.50 indicated the absence of significant fibrosis and an index of \> 1.50 indicated the presence of significant fibrosis. A negative change from Baseline indicates decreased fibrosis. |
| Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Baseline (Month 0) to Months 15, 18 and 24 | APRI is the ratio of aspartate aminotransferase (AST) to platelet count. It is calculated using formula, APRI = (AST level \[/ULN\] / platelet counts \[10\^9/L\]) \* 100. An APRI index of \<=0.50 indicated the absence of significant fibrosis and an index of \> 1.50 indicated the presence of significant fibrosis. A negative change from Baseline indicates decreased fibrosis. |
| Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Baseline (Month 0) to Months 3, 6 and 12 | Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis. |
| Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Baseline (Month 0) to Months 15, 18 and 24 | Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis. |
| Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Baseline (Month 0) to Months 6 and 12 | Hyaluronic acid is a non-invasive hepatic fibrosis marker. A negative change from Baseline indicates decreased fibrosis. |
| Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Baseline (Month 0) to Months 18 and 24 | Hyaluronic acid is a non-invasive hepatic fibrosis marker. A positive change from Baseline indicates increased fibrosis. |
| Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Baseline (Month 0) to Months 3, 6 and 12 | NFS is calculated using formula: NFS = -1.675 + 0.037 \* age (years) + 0.094 \* Body mass index (BMI) (kg/m\^2) + 1.13 \* Impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 \* Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio - 0.013 × platelet (\*10\^9/L) - 0.66 \* albumin (g/dL). A negative change from Baseline indicates decreased fibrosis. |
| Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Baseline (Month 0) to Months 15, 18 and 24 | NFS is calculated using formula: NFS = -1.675 + 0.037 \* age (years) + 0.094 \* Body mass index (BMI) (kg/m\^2) + 1.13 \* Impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 \* Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio - 0.013 × platelet (\*10\^9/L) - 0.66 \* albumin (g/dL). A negative change from Baseline indicates decreased fibrosis. |
| Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Baseline (Month 0) to Months 6 and 12 | The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF 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. |
| Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Baseline (Month 0) to Months 18 and 24 | The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF 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. |
| Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Baseline (Month 0) to Months 3, 6 and 12 | Caspase-cleaved cytokeratin levels (CK18M30) and total M-65 (CK-18 \[M-65\]) were measured as biomarkers of hepatocyte apoptosis. A negative change from Baseline indicates decreased hepatocyte apoptosis. |
| Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | Baseline (Month 0) to Months 15, 18 and 24 | Caspase-cleaved cytokeratin levels (CK18M30) and total M-65 (CK-18 \[M-65\]) were measured as biomarkers of hepatocyte apoptosis. A negative change from Baseline indicates decreased hepatocyte apoptosis. |
| Change From Baseline in Weight at Months 3, 6 and 12 | Baseline (Day 1) to Months 3, 6 and 12 | A negative change from Baseline represents decreased weight. |
| Change From Baseline in Weight at Months 15, 18 and 24 | Baseline (Day 1) to Months 15, 18 and 24 | A negative change from Baseline represents decreased weight. |
| Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Baseline (Day 1) to Months 3, 6 and 12 | The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI. |
| Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Baseline (Day 1) to Months 15, 18 and 24 | The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI. |
| Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Baseline (Day 1) to Months 3, 6 and 12 | A negative change from Baseline represents decreased in waist circumference. |
| Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Baseline (Day 1) to Months 15, 18 and 24 | A negative change from Baseline represents decreased in waist circumference. |
| Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1 | Year 1 | Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. |
| Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Baseline (Day 1) to Months 15, 18 and 24 | A negative change from Baseline represents decreased hip circumference. |
| Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Baseline (Day 1) to Months 3, 6 and 12 | A negative change from Baseline represents decreased forearm circumference. |
| Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Baseline (Day 1) to Months 15, 18 and 24 | A negative change from Baseline represents decreased forearm circumference. |
| Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Baseline (Day 1) to Months 3, 6 and 12 | A negative change from Baseline represents decreased Tricep Skinfold Thickness. |
| Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Baseline (Day 1) to Months 15, 18 and 24 | A negative change from Baseline represents decreased Tricep Skinfold Thickness. |
| Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Baseline (Day 1) to Months 3, 6 and 12 | A negative change from Baseline represents decreased hip circumference. |
Countries
Australia, Belgium, France, Germany, Hong Kong, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
In total, 812 participants were screened, and 289 participants were randomized to treatment period 1. Of the 289 participants randomized, 250 participants completed Treatment Period 1. A total of 242 participants entered Treatment Period 2 and 212 completed.
Participants by arm
| Arm | Count |
|---|---|
| CVC 150mg/CVC 150 mg CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2. | 145 |
| Placebo/Cenicriviroc (CVC) 150 mg Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2. | 72 |
| Placebo/Placebo Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2. | 72 |
| Total | 289 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Discontinued After Period 1 | Adverse Event | 1 | 2 | 0 |
| Discontinued After Period 1 | Participant Withdrew Consent | 1 | 1 | 2 |
| Discontinued After Period 1 | Physician Decision | 0 | 0 | 1 |
| Treatment Period 1 (Year 1) | Adverse Event | 4 | 5 | 9 |
| Treatment Period 1 (Year 1) | Lost to Follow-up | 1 | 0 | 0 |
| Treatment Period 1 (Year 1) | Other Miscellaneous Reasons | 0 | 0 | 1 |
| Treatment Period 1 (Year 1) | Protocol Deviation (with non-compliance) | 0 | 1 | 0 |
| Treatment Period 1 (Year 1) | Subject Withdrew Consent | 5 | 2 | 11 |
| Treatment Period 2 (Year 2) | Adverse Event | 0 | 1 | 5 |
| Treatment Period 2 (Year 2) | Lost to Follow-up | 0 | 1 | 2 |
| Treatment Period 2 (Year 2) | Other Miscellaneous Reasons | 0 | 0 | 1 |
| Treatment Period 2 (Year 2) | Physician Decision | 0 | 0 | 2 |
| Treatment Period 2 (Year 2) | Subject Withdrew Consent | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo/Placebo | Placebo/Cenicriviroc (CVC) 150 mg | CVC 150mg/CVC 150 mg |
|---|---|---|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 10.59 | 52.1 years STANDARD_DEVIATION 11.37 | 55.3 years STANDARD_DEVIATION 10.38 | 54.6 years STANDARD_DEVIATION 10.22 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants | 9 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 48 Participants | 7 Participants | 18 Participants | 23 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 238 Participants | 65 Participants | 51 Participants | 122 Participants |
| Race/Ethnicity, Customized Not reported | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 250 Participants | 58 Participants | 63 Participants | 129 Participants |
| Sex: Female, Male Female | 152 Participants | 40 Participants | 39 Participants | 73 Participants |
| Sex: Female, Male Male | 137 Participants | 32 Participants | 33 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 144 | 0 / 72 | 0 / 72 |
| other Total, other adverse events | 127 / 144 | 59 / 72 | 60 / 72 |
| serious Total, serious adverse events | 25 / 144 | 8 / 72 | 12 / 72 |
Outcome results
Primary
Number of Participant With Hepatic Histological Improvement in NAS by ≥ 2 Points With at Least 1-Point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and no Concurrent Worsening of Fibrosis at Year 1
Hepatic histological improvement in Nonalcoholic Fatty Liver Disease Activity Score (NAS) at Year 1 was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Evaluation of fibrosis stage was based on the nonalcoholic steatohepatitis clinical research network (NASH CRN) fibrosis staging system, which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. Worsening of fibrosis stage was defined as progression of NASH CRN fibrosis stage.
Time frame: Year 1
Population: Intent-to-treat (ITT) population included all randomized participants regardless of starting treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participant With Hepatic Histological Improvement in NAS by ≥ 2 Points With at Least 1-Point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and no Concurrent Worsening of Fibrosis at Year 1 | 27 Participants |
| CVC 150 mg | Number of Participant With Hepatic Histological Improvement in NAS by ≥ 2 Points With at Least 1-Point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and no Concurrent Worsening of Fibrosis at Year 1 | 23 Participants |
p-value: 0.519495% CI: [0.439, 1.516]Regression, Logistic
Secondary
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24
Caspase-cleaved cytokeratin levels (CK18M30) and total M-65 (CK-18 \[M-65\]) were measured as biomarkers of hepatocyte apoptosis. A negative change from Baseline indicates decreased hepatocyte apoptosis.
Time frame: Baseline (Month 0) to Months 15, 18 and 24
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Baseline (Month 15) | 570.8 U/L | Standard Deviation 297.42 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Change from Baseline to Month 15 | -39.6 U/L | Standard Deviation 287.44 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Baseline (Month 18) | 578.8 U/L | Standard Deviation 293.93 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Change from Baseline to Month 18 | 23.8 U/L | Standard Deviation 402.98 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Baseline (Month 24) | 575.4 U/L | Standard Deviation 293.64 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Change from Baseline to Month 24 | -30.0 U/L | Standard Deviation 369.6 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Baseline (Month 15) | 772.7 U/L | Standard Deviation 337.24 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Change from Baseline to Month 15 | 134.7 U/L | Standard Deviation 534.46 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Baseline (Month 18) | 777.8 U/L | Standard Deviation 344.07 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Change from Baseline to Month 18 | 158.0 U/L | Standard Deviation 732.63 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Baseline (Month 24) | 770.2 U/L | Standard Deviation 335.05 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Change from Baseline to Month 24 | 7.4 U/L | Standard Deviation 570.92 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Baseline (Month 24) | 693.9 U/L | Standard Deviation 409.88 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Baseline (Month 15) | 536.4 U/L | Standard Deviation 459.06 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Baseline (Month 15) | 687.4 U/L | Standard Deviation 404.83 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Change from Baseline to Month 15 | -13.3 U/L | Standard Deviation 450.16 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Change from Baseline to Month 18 | 181.5 U/L | Standard Deviation 620.57 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Baseline (Month 18) | 540.9 U/L | Standard Deviation 453.9 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Change from Baseline to Month 15 | 88.6 U/L | Standard Deviation 559.11 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Change from Baseline to Month 18 | 57.3 U/L | Standard Deviation 476.92 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Change from Baseline to Month 24 | 124.9 U/L | Standard Deviation 522.08 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Baseline (Month 24) | 541.8 U/L | Standard Deviation 462.29 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M65), Baseline (Month 18) | 694.8 U/L | Standard Deviation 401.88 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24 | CK-18(M30), Change from Baseline to Month 24 | 39.7 U/L | Standard Deviation 437.6 |
Secondary
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12
Caspase-cleaved cytokeratin levels (CK18M30) and total M-65 (CK-18 \[M-65\]) were measured as biomarkers of hepatocyte apoptosis. A negative change from Baseline indicates decreased hepatocyte apoptosis.
Time frame: Baseline (Month 0) to Months 3, 6 and 12
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Baseline (Month 3) | 601.6 U/L | Standard Deviation 431.77 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Change from Baseline to Month 3 | -56.4 U/L | Standard Deviation 451.14 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Baseline (Month 6) | 550.3 U/L | Standard Deviation 360.64 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Change from Baseline to Month 6 | 10.6 U/L | Standard Deviation 461.98 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Baseline (Month 12) | 555.3 U/L | Standard Deviation 356.28 |
| Placebo | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Change from Baseline to Month 12 | 99.7 U/L | Standard Deviation 824.5 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Baseline (Month 12) | 567.9 U/L | Standard Deviation 500.53 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Baseline (Month 3) | 594.2 U/L | Standard Deviation 554.2 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Change from Baseline to Month 6 | -26.1 U/L | Standard Deviation 512.88 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Change from Baseline to Month 3 | -59.0 U/L | Standard Deviation 485.76 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Change from Baseline to Month 12 | 107.8 U/L | Standard Deviation 830.28 |
| CVC 150 mg | Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12 | Baseline (Month 6) | 552.9 U/L | Standard Deviation 393.92 |
Secondary
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24
The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI.
Time frame: Baseline (Day 1) to Months 15, 18 and 24
Population: Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Baseline (Month 15) | 34.713 kg/m^2 | Standard Deviation 8.0431 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Change from Baseline to Month 15 | -0.006 kg/m^2 | Standard Deviation 1.2799 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Baseline (Month 18) | 34.473 kg/m^2 | Standard Deviation 7.8964 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Change from Baseline to Month 18 | -0.039 kg/m^2 | Standard Deviation 1.5931 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Baseline (Month 24) | 34.473 kg/m^2 | Standard Deviation 7.8964 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Change from Baseline to Month 24 | -0.393 kg/m^2 | Standard Deviation 2.0613 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Baseline (Month 24) | 33.278 kg/m^2 | Standard Deviation 6.0012 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Baseline (Month 15) | 33.392 kg/m^2 | Standard Deviation 5.9669 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Change from Baseline to Month 18 | -0.040 kg/m^2 | Standard Deviation 1.7153 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Change from Baseline to Month 15 | -0.113 kg/m^2 | Standard Deviation 1.6311 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Change from Baseline to Month 24 | -0.178 kg/m^2 | Standard Deviation 1.8515 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 | Baseline (Month 18) | 33.345 kg/m^2 | Standard Deviation 5.9443 |
Secondary
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12
The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI.
Time frame: Baseline (Day 1) to Months 3, 6 and 12
Population: Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Baseline (Month 3) | 34.129 kg/m^2 | Standard Deviation 7.2492 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.172 kg/m^2 | Standard Deviation 0.92 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Baseline (Month 6) | 34.196 kg/m^2 | Standard Deviation 7.3086 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.182 kg/m^2 | Standard Deviation 1.1558 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Baseline (Month 12) | 34.029 kg/m^2 | Standard Deviation 7.1358 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.013 kg/m^2 | Standard Deviation 1.7507 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Baseline (Month 12) | 33.374 kg/m^2 | Standard Deviation 5.6631 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Baseline (Month 3) | 33.706 kg/m^2 | Standard Deviation 5.7812 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.196 kg/m^2 | Standard Deviation 1.25 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.232 kg/m^2 | Standard Deviation 0.95 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.145 kg/m^2 | Standard Deviation 1.4891 |
| CVC 150 mg | Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 | Baseline (Month 6) | 33.547 kg/m^2 | Standard Deviation 5.6037 |
Secondary
Change From Baseline in Forearm Circumference at Months 15, 18 and 24
A negative change from Baseline represents decreased forearm circumference.
Time frame: Baseline (Day 1) to Months 15, 18 and 24
Population: Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Baseline (Month 15) | 32.88 cm | Standard Deviation 7.783 |
| Placebo | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Change from Baseline to Month 15 | 1.61 cm | Standard Deviation 6.534 |
| Placebo | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Baseline (Month 18) | 32.63 cm | Standard Deviation 7.718 |
| Placebo | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Change from Baseline to Month 18 | 1.79 cm | Standard Deviation 6.715 |
| Placebo | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Baseline (Month 24) | 32.79 cm | Standard Deviation 7.66 |
| Placebo | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Change from Baseline to Month 24 | 0.78 cm | Standard Deviation 6.124 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Baseline (Month 24) | 33.02 cm | Standard Deviation 5.561 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Baseline (Month 15) | 32.91 cm | Standard Deviation 5.662 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.02 cm | Standard Deviation 4.709 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.01 cm | Standard Deviation 5.052 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Change from Baseline to Month 24 | -0.64 cm | Standard Deviation 4.408 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 15, 18 and 24 | Baseline (Month 18) | 32.87 cm | Standard Deviation 5.696 |
Secondary
Change From Baseline in Forearm Circumference at Months 3, 6 and 12
A negative change from Baseline represents decreased forearm circumference.
Time frame: Baseline (Day 1) to Months 3, 6 and 12
Population: Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Baseline (Month 3) | 32.95 cm | Standard Deviation 7.346 |
| Placebo | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.97 cm | Standard Deviation 6.023 |
| Placebo | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.82 cm | Standard Deviation 6.748 |
| Placebo | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Baseline (Month 12) | 32.51 cm | Standard Deviation 7.277 |
| Placebo | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.83 cm | Standard Deviation 6.656 |
| Placebo | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Baseline (Month 6) | 32.70 cm | Standard Deviation 7.29 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.43 cm | Standard Deviation 3.516 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Baseline (Month 3) | 33.38 cm | Standard Deviation 4.835 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Baseline (Month 12) | 33.09 cm | Standard Deviation 4.771 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.10 cm | Standard Deviation 6.486 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Baseline (Month 6) | 33.25 cm | Standard Deviation 4.734 |
| CVC 150 mg | Change From Baseline in Forearm Circumference at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.01 cm | Standard Deviation 3.447 |
Secondary
Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1
The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 1. A positive change from Baseline indicates worsening.
Time frame: Baseline (Day 1) to Year 1
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1 | Baseline | 2.41 percentage of α-SMA positive cells/area | Standard Deviation 2.264 |
| Placebo | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1 | Change from Baseline to Year 1 | 0.77 percentage of α-SMA positive cells/area | Standard Deviation 3.529 |
| CVC 150 mg | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1 | Baseline | 2.49 percentage of α-SMA positive cells/area | Standard Deviation 2.885 |
| CVC 150 mg | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1 | Change from Baseline to Year 1 | 0.79 percentage of α-SMA positive cells/area | Standard Deviation 3.861 |
Secondary
Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2
The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 2. A positive change from Baseline indicates worsening.
Time frame: Baseline (Day 1) to Year 2
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 | Baseline | 2.47 percentage of α-SMA positive cells/area | Standard Deviation 2.679 |
| Placebo | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 | Change from Baseline to Year 2 | 2.10 percentage of α-SMA positive cells/area | Standard Deviation 4.533 |
| CVC 150 mg | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 | Baseline | 2.44 percentage of α-SMA positive cells/area | Standard Deviation 2.505 |
| CVC 150 mg | Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 | Change from Baseline to Year 2 | 1.38 percentage of α-SMA positive cells/area | Standard Deviation 3.793 |
Secondary
Change From Baseline in Hip Circumference at Months 15, 18 and 24
A negative change from Baseline represents decreased hip circumference.
Time frame: Baseline (Day 1) to Months 15, 18 and 24
Population: Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Baseline (Month 15) | 114.56 cm | Standard Deviation 17.5 |
| Placebo | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Change from Baseline to Month 15 | -0.06 cm | Standard Deviation 5.361 |
| Placebo | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Baseline (Month 18) | 114.28 cm | Standard Deviation 17.871 |
| Placebo | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.55 cm | Standard Deviation 7.791 |
| Placebo | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Baseline (Month 24) | 114.34 cm | Standard Deviation 17.408 |
| Placebo | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Change from Baseline to Month 24 | -0.95 cm | Standard Deviation 7.7 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Baseline (Month 24) | 112.88 cm | Standard Deviation 14.225 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Baseline (Month 15) | 113.00 cm | Standard Deviation 14.183 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Change from Baseline to Month 18 | -0.90 cm | Standard Deviation 6.066 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Change from Baseline to Month 15 | -0.83 cm | Standard Deviation 7.05 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Change from Baseline to Month 24 | -1.21 cm | Standard Deviation 6.677 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 15, 18 and 24 | Baseline (Month 18) | 112.70 cm | Standard Deviation 14.168 |
Secondary
Change From Baseline in Hip Circumference at Months 3, 6 and 12
A negative change from Baseline represents decreased hip circumference.
Time frame: Baseline (Day 1) to Months 3, 6 and 12
Population: Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Baseline (Month 3) | 114.92 cm | Standard Deviation 16.15 |
| Placebo | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.30 cm | Standard Deviation 4.921 |
| Placebo | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Baseline (Month 6) | 115.09 cm | Standard Deviation 16.27 |
| Placebo | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.84 cm | Standard Deviation 4.396 |
| Placebo | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Baseline (Month 12) | 114.46 cm | Standard Deviation 15.97 |
| Placebo | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.25 cm | Standard Deviation 5.876 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Baseline (Month 12) | 111.66 cm | Standard Deviation 13.376 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Baseline (Month 3) | 112.35 cm | Standard Deviation 13.802 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.18 cm | Standard Deviation 5.715 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.11 cm | Standard Deviation 6.475 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.08 cm | Standard Deviation 7.474 |
| CVC 150 mg | Change From Baseline in Hip Circumference at Months 3, 6 and 12 | Baseline (Month 6) | 112.16 cm | Standard Deviation 13.32 |
Secondary
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1
The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A positive change from Baseline indicates worsening.
Time frame: Baseline (Day 1) to Year 1
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Baseline (NASH CRN Fibrosis Stage) | 2.1 score on a scale | Standard Deviation 0.86 |
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Change from Baseline (NASH CRN Fibrosis Stage) | 0.2 score on a scale | Standard Deviation 0.92 |
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Baseline (Ishak Fibrosis Stage) | 2.2 score on a scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Change from Baseline (Ishak Fibrosis Stage) | 0.2 score on a scale | Standard Deviation 1.1 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Change from Baseline (Ishak Fibrosis Stage) | 0.0 score on a scale | Standard Deviation 1.2 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Baseline (NASH CRN Fibrosis Stage) | 2.0 score on a scale | Standard Deviation 0.85 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Baseline (Ishak Fibrosis Stage) | 2.2 score on a scale | Standard Deviation 1.05 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 | Change from Baseline (NASH CRN Fibrosis Stage) | 0.0 score on a scale | Standard Deviation 1 |
Secondary
Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2
The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) to Year 2
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Baseline (NASH CRN Fibrosis Stage) | 2.0 score on a scale | Standard Deviation 0.88 |
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Change from Baseline (NASH CRN Fibrosis Stage) | 0.0 score on a scale | Standard Deviation 0.89 |
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Baseline (Ishak Fibrosis Stage) | 2.1 score on a scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Change from Baseline (Ishak Fibrosis Stage) | 0.1 score on a scale | Standard Deviation 1.21 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Change from Baseline (Ishak Fibrosis Stage) | 0.0 score on a scale | Standard Deviation 1.26 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Baseline (NASH CRN Fibrosis Stage) | 2.1 score on a scale | Standard Deviation 0.85 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Baseline (Ishak Fibrosis Stage) | 2.2 score on a scale | Standard Deviation 1.04 |
| CVC 150 mg | Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 | Change from Baseline (NASH CRN Fibrosis Stage) | 0.0 score on a scale | Standard Deviation 1.08 |
Secondary
Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1
The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 1. A negative change from Baseline indicates improvement.
Time frame: Year 1
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1 | Baseline | 2.49 percent collagen area | Standard Deviation 2.004 |
| Placebo | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1 | Change from Baseline to Year 1 | -0.14 percent collagen area | Standard Deviation 2.389 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1 | Baseline | 2.37 percent collagen area | Standard Deviation 1.827 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1 | Change from Baseline to Year 1 | 0.02 percent collagen area | Standard Deviation 2.357 |
Secondary
Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2
The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 2. A negative change from Baseline indicates improvement.
Time frame: Year 2
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2 | Baseline | 2.57 percent collagen area | Standard Deviation 2.156 |
| Placebo | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2 | Change from Baseline to Year 2 | -0.17 percent collagen area | Standard Deviation 2.576 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2 | Baseline | 2.48 percent collagen area | Standard Deviation 1.892 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2 | Change from Baseline to Year 2 | -0.09 percent collagen area | Standard Deviation 2.16 |
Secondary
Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1
The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 1. A negative change from Baseline indicates improvement.
Time frame: Year 1
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1 | Baseline | 22.42 percent fat area | Standard Deviation 10.016 |
| Placebo | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1 | Change from Baseline to Year 1 | -3.39 percent fat area | Standard Deviation 9.12 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1 | Baseline | 21.58 percent fat area | Standard Deviation 8.74 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1 | Change from Baseline to Year 1 | -2.79 percent fat area | Standard Deviation 8.127 |
Secondary
Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2
The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 2. A negative change from Baseline indicates improvement.
Time frame: Year 2
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2 | Baseline | 23.30 percent fat area | Standard Deviation 10.3 |
| Placebo | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2 | Change from Baseline to Year 2 | -5.06 percent fat area | Standard Deviation 9.739 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2 | Baseline | 21.62 percent fat area | Standard Deviation 9.575 |
| CVC 150 mg | Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2 | Change from Baseline to Year 2 | -2.96 percent fat area | Standard Deviation 9.23 |
Secondary
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24
APRI is the ratio of aspartate aminotransferase (AST) to platelet count. It is calculated using formula, APRI = (AST level \[/ULN\] / platelet counts \[10\^9/L\]) \* 100. An APRI index of \<=0.50 indicated the absence of significant fibrosis and an index of \> 1.50 indicated the presence of significant fibrosis. A negative change from Baseline indicates decreased fibrosis.
Time frame: Baseline (Month 0) to Months 15, 18 and 24
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Baseline (Month 15) | 0.619 ratio | Standard Deviation 0.3157 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.002 ratio | Standard Deviation 0.3422 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Baseline (Month 18) | 0.620 ratio | Standard Deviation 0.3305 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.038 ratio | Standard Deviation 0.4033 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Baseline (Month 24) | 0.633 ratio | Standard Deviation 0.3156 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Change from Baseline to Month 24 | -0.020 ratio | Standard Deviation 0.4721 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Baseline (Month 24) | 0.584 ratio | Standard Deviation 0.3617 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Baseline (Month 15) | 0.584 ratio | Standard Deviation 0.3572 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.133 ratio | Standard Deviation 0.4269 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.118 ratio | Standard Deviation 0.4095 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Change from Baseline to Month 24 | 0.086 ratio | Standard Deviation 0.4153 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 | Baseline (Month 18) | 0.586 ratio | Standard Deviation 0.3612 |
Secondary
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12
APRI is the ratio of aspartate aminotransferase (AST) to platelet count. It is calculated using formula, APRI = (AST level \[/ULN\] / platelet counts \[10\^9/L\]) \* 100. An APRI index of \<=0.50 indicated the absence of significant fibrosis and an index of \> 1.50 indicated the presence of significant fibrosis. A negative change from Baseline indicates decreased fibrosis.
Time frame: Baseline (Month 0) to Months 3, 6 and 12
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Baseline (Month 12) | 0.662 ratio | Standard Deviation 0.3915 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.005 ratio | Standard Deviation 0.3012 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Baseline (Month 6) | 0.663 ratio | Standard Deviation 0.3811 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.009 ratio | Standard Deviation 0.3968 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.066 ratio | Standard Deviation 0.5572 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Baseline (Month 3) | 0.649 ratio | Standard Deviation 0.3661 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.093 ratio | Standard Deviation 0.3852 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Baseline (Month 3) | 0.596 ratio | Standard Deviation 0.4089 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.102 ratio | Standard Deviation 0.4536 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.065 ratio | Standard Deviation 0.3152 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Baseline (Month 12) | 0.580 ratio | Standard Deviation 0.3939 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 | Baseline (Month 6) | 0.578 ratio | Standard Deviation 0.3794 |
Secondary
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24
Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.
Time frame: Baseline (Month 0) to Months 15, 18 and 24
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Baseline (Month 15) | 1.409 ratio | Standard Deviation 0.6706 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.075 ratio | Standard Deviation 0.5982 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Baseline (Month 18) | 1.389 ratio | Standard Deviation 0.6699 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.094 ratio | Standard Deviation 0.5891 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Baseline (Month 24) | 1.426 ratio | Standard Deviation 0.6841 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Change from Baseline to Month 24 | 0.064 ratio | Standard Deviation 0.8103 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Baseline (Month 24) | 1.444 ratio | Standard Deviation 0.6838 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Baseline (Month 15) | 1.440 ratio | Standard Deviation 0.6714 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.219 ratio | Standard Deviation 0.5559 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.213 ratio | Standard Deviation 0.6462 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Change from Baseline to Month 24 | 0.166 ratio | Standard Deviation 0.6086 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 | Baseline (Month 18) | 1.440 ratio | Standard Deviation 0.6895 |
Secondary
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12
Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.
Time frame: Baseline (Month 0) to Months 3, 6 and 12
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Baseline (Month 6) | 1.500 ratio | Standard Deviation 0.7268 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Baseline (Month 12) | 1.503 ratio | Standard Deviation 0.7442 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.021 ratio | Standard Deviation 0.4236 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.106 ratio | Standard Deviation 0.6876 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.015 ratio | Standard Deviation 0.4591 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Baseline (Month 3) | 1.444 ratio | Standard Deviation 0.6753 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.099 ratio | Standard Deviation 0.5246 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.071 ratio | Standard Deviation 0.4209 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Baseline (Month 6) | 1.388 ratio | Standard Deviation 0.6771 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Baseline (Month 3) | 1.417 ratio | Standard Deviation 0.6893 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Baseline (Month 12) | 1.398 ratio | Standard Deviation 0.6834 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.117 ratio | Standard Deviation 0.5069 |
Secondary
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24
Hyaluronic acid is a non-invasive hepatic fibrosis marker. A positive change from Baseline indicates increased fibrosis.
Time frame: Baseline (Month 0) to Months 18 and 24
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Baseline (Month 18) | 46.4 ng/mL | Standard Deviation 32.67 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Change from Baseline to Month 18 | 5.7 ng/mL | Standard Deviation 34.66 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Baseline (Month 24) | 46.6 ng/mL | Standard Deviation 32.91 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Change from Baseline to Month 24 | 19.3 ng/mL | Standard Deviation 70.64 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Change from Baseline to Month 24 | 13.0 ng/mL | Standard Deviation 95 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Baseline (Month 18) | 79.6 ng/mL | Standard Deviation 111.36 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Baseline (Month 24) | 79.7 ng/mL | Standard Deviation 112.46 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 | Change from Baseline to Month 18 | 1.4 ng/mL | Standard Deviation 81.2 |
Secondary
Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12
Hyaluronic acid is a non-invasive hepatic fibrosis marker. A negative change from Baseline indicates decreased fibrosis.
Time frame: Baseline (Month 0) to Months 6 and 12
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Baseline (Month 6) | 68.7 ng/mL | Standard Deviation 107.63 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Change from Baseline to Month 6 | -2.4 ng/mL | Standard Deviation 75.03 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Baseline (Month 12) | 70.7 ng/mL | Standard Deviation 110.49 |
| Placebo | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Change from Baseline to Month 12 | -0.2 ng/mL | Standard Deviation 81.3 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Change from Baseline to Month 12 | 10.9 ng/mL | Standard Deviation 58.46 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Baseline (Month 6) | 68.2 ng/mL | Standard Deviation 78.88 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Baseline (Month 12) | 69.5 ng/mL | Standard Deviation 80.56 |
| CVC 150 mg | Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 | Change from Baseline to Month 6 | 10.7 ng/mL | Standard Deviation 79.58 |
Secondary
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24
The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF 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.
Time frame: Baseline (Month 0) to Months 18 and 24
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Baseline (Month 18) | -0.931 ng/mL | Standard Deviation 0.6387 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Change from Baseline to Month 18 | -0.129 ng/mL | Standard Deviation 0.6606 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Baseline (Month 24) | -0.940 ng/mL | Standard Deviation 0.6587 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Change from Baseline to Month 24 | -0.024 ng/mL | Standard Deviation 0.7375 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Change from Baseline to Month 24 | 0.096 ng/mL | Standard Deviation 0.6437 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Baseline (Month 18) | -0.758 ng/mL | Standard Deviation 0.7307 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Baseline (Month 24) | -0.765 ng/mL | Standard Deviation 0.7127 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 | Change from Baseline to Month 18 | -0.087 ng/mL | Standard Deviation 0.6113 |
Secondary
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12
The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF 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.
Time frame: Baseline (Month 0) to Months 6 and 12
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Baseline (Month 6) | -0.786 ng/mL | Standard Deviation 0.7179 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Change from Baseline to Month 6 | -0.022 ng/mL | Standard Deviation 0.4901 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Baseline (Month 12) | -0.795 ng/mL | Standard Deviation 0.7435 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Change from Baseline to Month 12 | -0.064 ng/mL | Standard Deviation 0.5602 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Change from Baseline to Month 12 | 0.041 ng/mL | Standard Deviation 0.5727 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Baseline (Month 6) | -0.837 ng/mL | Standard Deviation 0.7238 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Baseline (Month 12) | -0.801 ng/mL | Standard Deviation 0.7162 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 | Change from Baseline to Month 6 | 0.060 ng/mL | Standard Deviation 0.5228 |
Secondary
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24
NFS is calculated using formula: NFS = -1.675 + 0.037 \* age (years) + 0.094 \* Body mass index (BMI) (kg/m\^2) + 1.13 \* Impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 \* Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio - 0.013 × platelet (\*10\^9/L) - 0.66 \* albumin (g/dL). A negative change from Baseline indicates decreased fibrosis.
Time frame: Baseline (Month 0) to Months 15, 18 and 24
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Change from Baseline to Month 24 | 0.046 ng/mL | Standard Deviation 0.6188 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.057 ng/mL | Standard Deviation 0.5981 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Baseline (Month 18) | -1.284 ng/mL | Standard Deviation 1.491 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.046 ng/mL | Standard Deviation 0.5809 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Baseline (Month 24) | -1.245 ng/mL | Standard Deviation 1.4778 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Baseline (Month 15) | -1.252 ng/mL | Standard Deviation 1.4602 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Baseline (Month 24) | -1.100 ng/mL | Standard Deviation 1.3228 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Baseline (Month 15) | -1.051 ng/mL | Standard Deviation 1.341 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.196 ng/mL | Standard Deviation 0.5583 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.225 ng/mL | Standard Deviation 0.5654 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Change from Baseline to Month 24 | 0.185 ng/mL | Standard Deviation 0.6184 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 | Baseline (Month 18) | -1.057 ng/mL | Standard Deviation 1.3309 |
Secondary
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12
NFS is calculated using formula: NFS = -1.675 + 0.037 \* age (years) + 0.094 \* Body mass index (BMI) (kg/m\^2) + 1.13 \* Impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 \* Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio - 0.013 × platelet (\*10\^9/L) - 0.66 \* albumin (g/dL). A negative change from Baseline indicates decreased fibrosis.
Time frame: Baseline (Month 0) to Months 3, 6 and 12
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Baseline (Month 3) | -1.227 ng/mL | Standard Deviation 1.5255 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.029 ng/mL | Standard Deviation 0.515 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Baseline (Month 6) | -1.119 ng/mL | Standard Deviation 1.4935 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.051 ng/mL | Standard Deviation 0.4747 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Baseline (Month 12) | -1.132 ng/mL | Standard Deviation 1.4609 |
| Placebo | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.121 ng/mL | Standard Deviation 0.5117 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Baseline (Month 12) | -1.040 ng/mL | Standard Deviation 1.1393 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Baseline (Month 3) | -1.012 ng/mL | Standard Deviation 1.2558 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.094 ng/mL | Standard Deviation 0.546 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.087 ng/mL | Standard Deviation 0.4608 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.139 ng/mL | Standard Deviation 0.5016 |
| CVC 150 mg | Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 | Baseline (Month 6) | -1.064 ng/mL | Standard Deviation 1.2403 |
Secondary
Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1
Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.
Time frame: Baseline (Day 1) to Year 1
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 | Baseline | 1.6 score on a scale | Standard Deviation 0.63 |
| Placebo | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 | Change from Baseline to Year 1 | 0.0 score on a scale | Standard Deviation 0.76 |
| CVC 150 mg | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 | Baseline | 1.5 score on a scale | Standard Deviation 0.64 |
| CVC 150 mg | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 | Change from Baseline to Year 1 | 0.2 score on a scale | Standard Deviation 0.74 |
Secondary
Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2
Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.
Time frame: Baseline (Day 1) to Year 2
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 | Baseline | 1.5 score on a scale | Standard Deviation 0.64 |
| Placebo | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 | Change from Baseline to Year 1 | 0.1 score on a scale | Standard Deviation 0.75 |
| CVC 150 mg | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 | Baseline | 1.6 score on a scale | Standard Deviation 0.67 |
| CVC 150 mg | Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 | Change from Baseline to Year 1 | 0.2 score on a scale | Standard Deviation 0.72 |
Secondary
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1
NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= \<5%, 1= 5 - 33%, 2= \>33 - 66%, and 3= \>66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= \< 2 foci/200x, 2= 2-4 foci/200x, and 3= \> 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement.
Time frame: Year 1
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Baseline (Steatosis) | 1.4 score on a scale | Standard Deviation 0.55 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Change from Baseline (Steatosis) | -0.1 score on a scale | Standard Deviation 0.66 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Baseline (Lobular Inflammation) | 2.5 score on a scale | Standard Deviation 0.56 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Change from Baseline (Lobular Inflammation) | -0.1 score on a scale | Standard Deviation 0.79 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Baseline (Hepatocellular Ballooning) | 1.5 score on a scale | Standard Deviation 0.5 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Change from Baseline (Hepatocellular Ballooning) | -0.2 score on a scale | Standard Deviation 0.75 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Baseline (Hepatocellular Ballooning) | 1.5 score on a scale | Standard Deviation 0.5 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Baseline (Steatosis) | 1.3 score on a scale | Standard Deviation 0.57 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Change from Baseline (Lobular Inflammation) | -0.1 score on a scale | Standard Deviation 0.88 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Change from Baseline (Steatosis) | -0.2 score on a scale | Standard Deviation 0.56 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Change from Baseline (Hepatocellular Ballooning) | -0.1 score on a scale | Standard Deviation 0.75 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1 | Baseline (Lobular Inflammation) | 2.4 score on a scale | Standard Deviation 0.58 |
Secondary
Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2
NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= \<5%, 1= 5 - 33%, 2= \>33 - 66%, and 3= \>66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= \< 2 foci/200x, 2= 2-4 foci/200x, and 3= \> 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement.
Time frame: Year 2
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Baseline (Steatosis) | 1.5 score on a scale | Standard Deviation 0.54 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Change from Baseline (Steatosis) | -0.4 score on a scale | Standard Deviation 0.56 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Baseline (Lobular Inflammation) | 2.4 score on a scale | Standard Deviation 0.63 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Change from Baseline (Lobular Inflammation) | 0.1 score on a scale | Standard Deviation 0.72 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Baseline (Hepatocellular Ballooning) | 1.5 score on a scale | Standard Deviation 0.5 |
| Placebo | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Change from Baseline (Hepatocellular Ballooning) | -0.1 score on a scale | Standard Deviation 0.68 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Baseline (Hepatocellular Ballooning) | 1.5 score on a scale | Standard Deviation 0.5 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Baseline (Steatosis) | 1.3 score on a scale | Standard Deviation 0.52 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Change from Baseline (Lobular Inflammation) | 0.0 score on a scale | Standard Deviation 0.84 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Change from Baseline (Steatosis) | -0.2 score on a scale | Standard Deviation 0.5 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Change from Baseline (Hepatocellular Ballooning) | 0.0 score on a scale | Standard Deviation 0.83 |
| CVC 150 mg | Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2 | Baseline (Lobular Inflammation) | 2.4 score on a scale | Standard Deviation 0.54 |
Secondary
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24
A negative change from Baseline represents decreased Tricep Skinfold Thickness.
Time frame: Baseline (Day 1) to Months 15, 18 and 24
Population: Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Baseline (Month 15) | 29.84 mm | Standard Deviation 14.422 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Change from Baseline to Month 15 | -1.45 mm | Standard Deviation 9.364 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Baseline (Month 18) | 29.84 mm | Standard Deviation 14.655 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Change from Baseline to Month 18 | -2.27 mm | Standard Deviation 8.854 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Baseline (Month 24) | 29.91 mm | Standard Deviation 14.532 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Change from Baseline to Month 24 | -3.11 mm | Standard Deviation 8.553 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Change from Baseline to Month 18 | -2.64 mm | Standard Deviation 8.864 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Baseline (Month 15) | 25.41 mm | Standard Deviation 13.212 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Change from Baseline to Month 24 | -1.33 mm | Standard Deviation 10.521 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Change from Baseline to Month 15 | -1.59 mm | Standard Deviation 8.918 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Baseline (Month 24) | 24.82 mm | Standard Deviation 13.025 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 | Baseline (Month 18) | 25.07 mm | Standard Deviation 12.856 |
Secondary
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12
A negative change from Baseline represents decreased Tricep Skinfold Thickness.
Time frame: Baseline (Day 1) to Months 3, 6 and 12
Population: Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Baseline (Month 3) | 28.32 mm | Standard Deviation 13.677 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Change from Baseline to Month 3 | -1.21 mm | Standard Deviation 6.548 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Baseline (Month 6) | 28.53 mm | Standard Deviation 13.763 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Change from Baseline to Month 6 | -2.72 mm | Standard Deviation 8.091 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Baseline (Month 12) | 28.54 mm | Standard Deviation 13.981 |
| Placebo | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Change from Baseline to Month 12 | -1.34 mm | Standard Deviation 9.389 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Baseline (Month 12) | 25.14 mm | Standard Deviation 12.969 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Baseline (Month 3) | 25.41 mm | Standard Deviation 12.593 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Change from Baseline to Month 6 | -1.52 mm | Standard Deviation 9.287 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.62 mm | Standard Deviation 8.704 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.26 mm | Standard Deviation 10.653 |
| CVC 150 mg | Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 | Baseline (Month 6) | 25.38 mm | Standard Deviation 12.769 |
Secondary
Change From Baseline in Waist Circumference at Months 15, 18 and 24
A negative change from Baseline represents decreased in waist circumference.
Time frame: Baseline (Day 1) to Months 15, 18 and 24
Population: Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Baseline (Month 15) | 110.19 cm | Standard Deviation 14.36 |
| Placebo | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.52 cm | Standard Deviation 5.52 |
| Placebo | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Baseline (Month 18) | 109.48 cm | Standard Deviation 12.703 |
| Placebo | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Change from Baseline to Month 18 | 1.36 cm | Standard Deviation 7.966 |
| Placebo | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Baseline (Month 24) | 109.36 cm | Standard Deviation 12.608 |
| Placebo | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Change from Baseline to Month 24 | 0.11 cm | Standard Deviation 7.907 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Baseline (Month 24) | 110.08 cm | Standard Deviation 14.606 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Baseline (Month 15) | 110.26 cm | Standard Deviation 14.486 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Change from Baseline to Month 18 | -0.21 cm | Standard Deviation 6.578 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Change from Baseline to Month 15 | -0.18 cm | Standard Deviation 6.28 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Change from Baseline to Month 24 | -1.00 cm | Standard Deviation 6.503 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 15, 18 and 24 | Baseline (Month 18) | 110.25 cm | Standard Deviation 14.517 |
Secondary
Change From Baseline in Waist Circumference at Months 3, 6 and 12
A negative change from Baseline represents decreased in waist circumference.
Time frame: Baseline (Day 1) to Months 3, 6 and 12
Population: Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Baseline (Month 3) | 110.35 cm | Standard Deviation 14.866 |
| Placebo | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.07 cm | Standard Deviation 5.147 |
| Placebo | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Baseline (Month 6) | 110.42 cm | Standard Deviation 14.986 |
| Placebo | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Change from Baseline to Month 6 | 0.42 cm | Standard Deviation 8.827 |
| Placebo | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Baseline (Month 12) | 109.77 cm | Standard Deviation 14.617 |
| Placebo | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Change from Baseline to Month 12 | 0.44 cm | Standard Deviation 6.584 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Baseline (Month 12) | 110.02 cm | Standard Deviation 13.711 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Baseline (Month 3) | 110.25 cm | Standard Deviation 13.406 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.54 cm | Standard Deviation 5.876 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Change from Baseline to Month 3 | 0.05 cm | Standard Deviation 5.396 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Change from Baseline to Month 12 | -1.10 cm | Standard Deviation 6.255 |
| CVC 150 mg | Change From Baseline in Waist Circumference at Months 3, 6 and 12 | Baseline (Month 6) | 110.12 cm | Standard Deviation 13.561 |
Secondary
Change From Baseline in Weight at Months 15, 18 and 24
A negative change from Baseline represents decreased weight.
Time frame: Baseline (Day 1) to Months 15, 18 and 24
Population: Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Weight at Months 15, 18 and 24 | Baseline (Month 15) | 98.25 kg | Standard Deviation 24.087 |
| Placebo | Change From Baseline in Weight at Months 15, 18 and 24 | Change from Baseline to Month 15 | 0.15 kg | Standard Deviation 3.448 |
| Placebo | Change From Baseline in Weight at Months 15, 18 and 24 | Baseline (Month 18) | 96.98 kg | Standard Deviation 22.21 |
| Placebo | Change From Baseline in Weight at Months 15, 18 and 24 | Change from Baseline to Month 18 | 0.05 kg | Standard Deviation 4.194 |
| Placebo | Change From Baseline in Weight at Months 15, 18 and 24 | Baseline (Month 24) | 96.98 kg | Standard Deviation 22.21 |
| Placebo | Change From Baseline in Weight at Months 15, 18 and 24 | Change from Baseline to Month 24 | -0.91 kg | Standard Deviation 5.649 |
| CVC 150 mg | Change From Baseline in Weight at Months 15, 18 and 24 | Baseline (Month 24) | 95.19 kg | Standard Deviation 20.972 |
| CVC 150 mg | Change From Baseline in Weight at Months 15, 18 and 24 | Baseline (Month 15) | 95.32 kg | Standard Deviation 20.749 |
| CVC 150 mg | Change From Baseline in Weight at Months 15, 18 and 24 | Change from Baseline to Month 18 | -0.16 kg | Standard Deviation 4.458 |
| CVC 150 mg | Change From Baseline in Weight at Months 15, 18 and 24 | Change from Baseline to Month 15 | -0.44 kg | Standard Deviation 4.257 |
| CVC 150 mg | Change From Baseline in Weight at Months 15, 18 and 24 | Change from Baseline to Month 24 | -0.56 kg | Standard Deviation 5.081 |
| CVC 150 mg | Change From Baseline in Weight at Months 15, 18 and 24 | Baseline (Month 18) | 95.23 kg | Standard Deviation 20.823 |
Secondary
Change From Baseline in Weight at Months 3, 6 and 12
A negative change from Baseline represents decreased weight.
Time frame: Baseline (Day 1) to Months 3, 6 and 12
Population: Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Weight at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.50 kg | Standard Deviation 2.652 |
| Placebo | Change From Baseline in Weight at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.55 kg | Standard Deviation 3.319 |
| Placebo | Change From Baseline in Weight at Months 3, 6 and 12 | Baseline (Month 3) | 97.21 kg | Standard Deviation 22.368 |
| Placebo | Change From Baseline in Weight at Months 3, 6 and 12 | Baseline (Month 12) | 96.63 kg | Standard Deviation 22.139 |
| Placebo | Change From Baseline in Weight at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.08 kg | Standard Deviation 4.301 |
| Placebo | Change From Baseline in Weight at Months 3, 6 and 12 | Baseline (Month 6) | 97.18 kg | Standard Deviation 22.224 |
| CVC 150 mg | Change From Baseline in Weight at Months 3, 6 and 12 | Change from Baseline to Month 12 | -0.28 kg | Standard Deviation 4.166 |
| CVC 150 mg | Change From Baseline in Weight at Months 3, 6 and 12 | Baseline (Month 3) | 95.59 kg | Standard Deviation 20.59 |
| CVC 150 mg | Change From Baseline in Weight at Months 3, 6 and 12 | Change from Baseline to Month 3 | -0.63 kg | Standard Deviation 2.632 |
| CVC 150 mg | Change From Baseline in Weight at Months 3, 6 and 12 | Baseline (Month 6) | 95.18 kg | Standard Deviation 20.386 |
| CVC 150 mg | Change From Baseline in Weight at Months 3, 6 and 12 | Change from Baseline to Month 6 | -0.47 kg | Standard Deviation 3.466 |
| CVC 150 mg | Change From Baseline in Weight at Months 3, 6 and 12 | Baseline (Month 12) | 95.06 kg | Standard Deviation 20.651 |
Secondary
Number of Participants With Clinical Laboratory Abnormalities
Grade 3-4 abnormal clinical laboratory values that occurred in ≥2% participants were reported. Criteria used for various parameters was:Fasting glucose Grade3:\>250 - 500 mg/dL and Grade4: \>500 mg/dL; Alanine aminotransferase(ALT)Grade3:\>5.0 - 20.0 ×Upper Limit of Normal(ULN)and Grade4:\>20.0 ×ULN; Aspartate aminotransferase(AST)Grade3: \>5.0 - 20.0 ×ULN and Grade4: \>20.0 ×ULN; Activated partial thromboplastin(APT)/Partial thromboplastin time(PTT)Grade3: \>2.5×ULN; Triglycerides Grade3 \>500 - 1000 mg/dL and Grade4: \>1000 mg/dL; Gamma-glutamyl transferase(GGT)Grade3: \>5.0 - 20.0 ×ULN and Grade4: \>20.0 ×ULN; Creatine kinase Grade 3: \>5.0 - 10.0 ×ULN and Grade4: \>10.0 ×ULN; Uric acid Grade3:(ULN - 10 mg/dL; ULN - 0.59 mmol/L) and Grade4: \>10 mg/dL; Amylase Grade3: \>2.0 - 5.0 ×ULN and Grade4: \>5.0 ×ULN; Lipase Grade3: \>2.0 - 5.0 xULN and Grade4: \>5.0 xULN; Phosphorus Grade3: \<2.0 - 1.0 mg/dL and Grade4: \<1.0 mg/dL and Absolute neutrophil Grade3: \<1.0 - 0.5 × 109/L and Grade4: \<0.5 × 109/L.
Time frame: Years 1 and 2
Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 3) | 8 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 3) | 17 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 3) | 6 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 4) | 1 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 4) | 11 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 3) | 6 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 3) | 9 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 4) | 2 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 4) | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 3) | 2 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 3) | 7 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 4) | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 4) | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 4) | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 3) | 5 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | APT/PTT (Grade 3) | 4 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 4) | 5 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 3) | 5 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 4) | 2 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 3) | 4 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 4) | 3 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 4) | 3 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 3) | 17 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 3) | 7 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 3) | 2 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 3) | 7 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 4) | 6 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 4) | 0 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 4) | 1 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 3) | 17 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 4) | 0 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 3) | 8 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 4) | 3 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 3) | 7 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 3) | 1 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 4) | 0 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 4) | 1 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 3) | 3 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | APT/PTT (Grade 3) | 2 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 4) | 0 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 4) | 2 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 3) | 13 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 4) | 0 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 4) | 0 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 3) | 10 Participants |
| CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 3) | 2 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 3) | 4 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 3) | 10 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 4) | 0 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 3) | 4 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 4) | 0 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 3) | 1 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 4) | 0 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | APT/PTT (Grade 3) | 1 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 3) | 6 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 4) | 2 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 3) | 8 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 4) | 1 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 3) | 1 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 3) | 4 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 4) | 5 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 4) | 2 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 3) | 3 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 4) | 3 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 3) | 2 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 4) | 0 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 3) | 3 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 4) | 1 Participants |
| Placebo/Placebo | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 4) | 3 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 4) | 1 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 3) | 2 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 3) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 4) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 4) | 1 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 4) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 3) | 5 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 3) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | APT/PTT (Grade 3) | 1 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 4) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 4) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 4) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 3) | 1 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 3) | 3 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 3) | 6 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 4) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 4) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 4) | 1 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 3) | 0 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 3) | 3 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 3) | 2 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 3) | 3 Participants |
| Placebo Then CVC 150 mg | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 4) | 6 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 3) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 4) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 3) | 4 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 3) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Triglycerides (Grade 3) | 2 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 3) | 2 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | GGT (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Amylase (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Phosphorus (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | APT/PTT (Grade 3) | 2 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 4) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 3) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | ALT (Grade 3) | 2 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Creatine kinase (Grade 4) | 0 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Uric acid (Grade 3) | 2 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Lipase (Grade 4) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Absolute neutrophil (Grade 3) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | AST (Grade 3) | 1 Participants |
| Placebo Then Placebo | Number of Participants With Clinical Laboratory Abnormalities | Fasting glucose (Grade 3) | 5 Participants |
Secondary
Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings
A 12-lead ECG was performed. ECG results were reviewed by the Investigator for clinically notable abnormalities.
Time frame: Years 1 and 2
Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings | 0 Participants |
| CVC 150 mg | Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo/Placebo | Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs included blood pressure, temperature, heart rate, and respiration rate. Vital signs were reviewed by the Investigator for clinically significant changes.
Time frame: Years 1 and 2
Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| CVC 150 mg | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo/Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1
Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
Time frame: Year 1
Population: ITT population included all randomized participants regardless of starting treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1 | 4 Participants |
| CVC 150 mg | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1 | 7 Participants |
p-value: 0.038895% CI: [1.035, 3.614]Regression, Logistic
Secondary
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2
Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
Time frame: Year 2
Population: ITT population Year 2 included all participants who had an evaluable year 1 biopsy and received at least 1 dose of study drug during Year 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2 | 2 Participants |
| CVC 150 mg | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2 | 5 Participants |
p-value: 0.59295% CI: [0.553, 2.821]Regression, Logistic
Secondary
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1
Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
Time frame: Year 1
Population: ITT population included all randomized participants regardless of starting treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1 | 8 Participants |
| CVC 150 mg | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1 | 11 Participants |
p-value: 0.494195% CI: [0.537, 3.628]Regression, Logistic
Secondary
Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2
Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
Time frame: Year 2
Population: ITT population Year 2 included all participants who had an evaluable year 1 biopsy and received at least 1 dose of study drug during Year 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2 | 3 Participants |
| CVC 150 mg | Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2 | 11 Participants |
p-value: 0.843495% CI: [0.305, 4.277]Regression, Logistic
Secondary
Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation
A TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 30 days after the discontinuation of the study medication. An SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life threatening, requires hospitalization or results in prolongation of existing hospitalization, results in disability/incapacity, or was a congenital anomaly/birth defect.
Time frame: Years 1 and 2
Population: Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | Deaths | 0 Participants |
| Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | TEAEs | 137 Participants |
| Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | SAEs | 25 Participants |
| Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | TEAEs Leading Study Drug to Discontinuation | 14 Participants |
| CVC 150 mg | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | TEAEs Leading Study Drug to Discontinuation | 8 Participants |
| CVC 150 mg | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | Deaths | 0 Participants |
| CVC 150 mg | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | SAEs | 8 Participants |
| CVC 150 mg | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | TEAEs | 68 Participants |
| Placebo/Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | TEAEs Leading Study Drug to Discontinuation | 5 Participants |
| Placebo/Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | TEAEs | 70 Participants |
| Placebo/Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | SAEs | 12 Participants |
| Placebo/Placebo | Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation | Deaths | 0 Participants |
Secondary
Number of Participants With Hepatic Histological Improvement in NAS at Year 2
Hepatic histological improvement in NAS at Year 2 was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease.
Time frame: Year 2
Population: Full Analysis Set (FAS) in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Hepatic Histological Improvement in NAS at Year 2 | 7 Participants |
| CVC 150 mg | Number of Participants With Hepatic Histological Improvement in NAS at Year 2 | 24 Participants |
Secondary
Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-Point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1
Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either steatosis, lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Worsening was defined as progression of NASH CRN fibrosis stage.
Time frame: Year 1
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-Point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1 | 24 Participants |
| CVC 150 mg | Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-Point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1 | 22 Participants |
Secondary
Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2
Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either steatosis, lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Worsening was defined as progression of NASH CRN fibrosis stage.
Time frame: Year 2
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2 | 6 Participants |
| CVC 150 mg | Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2 | 20 Participants |
Secondary
Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1
The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade.
Time frame: Year 1
Population: ITT population included all randomized participants regardless of starting treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1 | 15 Participants |
| CVC 150 mg | Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1 | 29 Participants |
p-value: 0.023495% CI: [1.113, 4.352]Regression, Logistic
Secondary
Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2
The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade.
Time frame: Year 2
Population: ITT analysis set Year 2 included all participants who have an evaluable year 1 biopsy and who received at least one dose of study drug during Year 2 (after the 1 year biopsy).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2 | 8 Participants |
| CVC 150 mg | Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2 | 27 Participants |
p-value: 0.747495% CI: [0.484, 2.752]Regression, Logistic
Secondary
Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1
Resolution of NASH was defined as having no hepatocellular ballooning (grade 0) and minimal to no lobular inflammation (grade 1 or 0) with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH CRN fibrosis stage).
Time frame: Year 1
Population: FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1 | 7 Participants |
| CVC 150 mg | Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1 | 6 Participants |
Secondary
Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2
Resolution of NASH was defined as having no hepatocellular ballooning (grade 0) and minimal to no lobular inflammation (grade 1 or 0) with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH CRN fibrosis stage).
Time frame: Year 2
Population: FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2 | 1 Participants |
| CVC 150 mg | Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2 | 9 Participants |