Non-alcoholic Steatohepatitis, Fatty Liver, Fibrosis, Liver, Compensated Cirrhosis
Conditions
Brief summary
To evaluate the safety and tolerability of Nitazoxanide (NTZ) 500mg Twice Daily (BID) after 24 weeks of treatment in patients with NASH induced Stage 2 or Stage 3 fibrosis
Detailed description
Based on the anti-fibrotic properties demonstrated in the animal models of fibrosis, this proof of concept clinical study aims at evaluating NTZ in patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage 2 and 3. Although NTZ has been evaluated in liver disease populations up to 60 weeks, this is the first study evaluating NTZ treatment in a population with NASH induced stage 2 and 3 fibrosis. The aim of this study is to evaluate the safety and tolerability of NTZ 500 mg BID after 24 weeks of treatment in this population. This proof of concept study will also evaluate the anti-fibrotic effect of NTZ as a secondary objective. The methods of evaluation of fibrosis will include an innovative method of metabolic labeling.This approach is based on the concept that liver status can be determined by measuring the ratio of newly synthesized/pre-existing proteins.The turn-over rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients will be given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry is used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results are expressed as fractional synthesis rate of these proteins (FSR). This method has been previously published (Decaris et al, 2017). Other non-invasive methods will be used to evaluate the liver stiffness changes after NTZ treatment: Magnetic Resonance Elastography (MRE) and FibroScan®.
Interventions
Patients will receive 500mg of Nitazoxanide BID daily for 24 weeks
Sponsors
Pinnacle Clinical Research, PLLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females aged from 18 to 75 years inclusive the Screening Visit. 2. Must provide signed written informed consent and agree to comply with the study protocol. 3. Females participating in this study must be of non-childbearing potential or using highly efficient contraception for the full duration of the study 4. Histological confirmation of steatohepatitis on a diagnostic liver biopsy (biopsy obtained within 6 months prior to Screening or during the Screening Period) with at least 1 in each component of the NAS (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3). 5. Fibrosis stage of 2 or 3, according to the NASH Clinical Research Network fibrosis staging system on a diagnostic liver biopsy (biopsy obtained within 6 months prior to Screening or during the Screening Period). 6. Two assessments of ALT, AST, Total bilirubin, Alkaline phosphatase (ALP), Creatine phosphokinase (CPK) will be collected during screening at least 4 weeks apart. To be eligible the second value cannot be ≥2x the first value.
Exclusion criteria
1. History of efficient bariatric surgery within 5 years prior to Screening, or planned bariatric surgery in the course of the study. 2. Patients with HbA1c \>10.0%. If abnormal at the first Screening Visit, the HbA1c measurement can be repeated. A repeated abnormal HbA1c (HbA1c \>10.0%) leads to exclusion. 3. Patients with a history of clinically significant acute cardiac event within 6 months prior to Screening such as: stroke, transient ischemic attack, or coronary heart disease (angina pectoris, myocardial infarction, revascularization procedures). 4. Weight loss of more than 10% within 6 months prior to Randomization. 5. Patient with any history or presence of decompensated cirrhosis. 6. Current or recent history (\<1 year) of significant alcohol consumption. For men, significant consumption is typically defined as higher than 30 g pure alcohol per day. For women, it is typically defined as higher than 20 g pure alcohol per day. 7. Current or history of other substance abuse within 1 year prior to screening. 8. Pregnant or lactating females or females planning to become pregnant during the study period. 9. Other well documented causes of chronic liver disease according to standard diagnostic procedures including, but not restricted to: 1. Positive hepatitis B surface antigen (HBsAg) 2. Positive Hepatitis C virus (HCV) RNA, (tested for in case of known cured HCV infection, or positive HCV Ab at Screening) 3. Suspicion of drug-induced liver disease 4. Alcoholic liver disease 5. Autoimmune hepatitis 6. Wilson's disease 7. Primary biliary cirrhosis, primary sclerosing cholangitis 8. Genetic homozygous hemochromatosis 9. Known or suspected Hepatocellular Carcinoma 10. History or planned liver transplant, or current Model for End-Stage Liver Disease score \>15. 10. Patients who cannot be contacted in case of emergency. 11. Known hypersensitivity to the investigation product or any of its formulation excipients. 12. Patients who are taking warfarin or other highly plasma protein-bound drugs with narrow therapeutic indices. 13. Patients who are currently participating in, plan to participate in, or have participated in an investigational drug trial or medical device trial containing active substance within 30 days or five half-lives, whichever is longer, prior to Screening. 14. Evidence of any other unstable or, untreated clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic, or psychiatric disease. 15. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain. 16. History of noncompliance with medical regimens, or patients who are considered to be unreliable. 17. Positive anti-human immunodeficiency virus (HIV) antibody. 18. AST and/or ALT \>10 x upper limit of normal (ULN). 19. Total bilirubin \>1.3 mg/dL due to altered hepatic function. 20. Direct bilirubin \> ULN Note: Gilbert Disease patients are allowed into the study. 21. International Normalized Ratio \>1.2 in the absence of anticoagulant therapy. 22. Platelet count \<150,000/mm3 in the context of portal hypertension. 23. Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney damage or estimated glomerular filtration rate of less than 60 ml/min/1.73 m2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of treatment-emergent adverse events (TEAEs). |
| Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related treatment-emergent adverse events (TEAEs). |
| Number of NTZ Treated Participants Presenting Any SAE | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of serious adverse events (SAEs). |
| Number of NTZ Treated Participants Presenting Study Drug-Related SAE | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related serious adverse events (SAEs). |
| Deaths Due to AE | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of deaths due to adverse events (AEs). |
| Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of adverse events (AEs) leading to withdrawal from study or study drug. |
| Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related adverse events (AEs) leading to withdrawal from study or study drug |
| Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by performing clinical laboratory evaluations. Changes in clinical laboratory evaluations were considered clinically significant or not as per Investigator judgment. |
| Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by measuring vital signs. Changes in vital signs were considered clinically significant or not as per Investigator judgement |
| Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by performing electrocardiograms (ECGs). Changes in ECGs parameters were considered clinically significant or not as per Investigator judgement. |
| Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations | 28 weeks | To assess the safety and tolerability of NTZ after 24 weeks of treatment by conducting physical examinations. Changes in physical examinations were considered clinically significant or not as per Investigator judgement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Pro-C6 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment | From baseline to end of treatment (Visit 10, Week 24 or early termination) | Change in Lumican Fractional Synthesis Rate (FSR) from baseline to end of treatment evaluated through the use of deuterated water. Lumican is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. |
| Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment | From baseline to end of treatment (Visit 10, Week 24 or early termination) | Percent Change in Lumican FSR from baseline to end of treatment evaluated through the use of deuterated water. Lumican is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. |
| Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment | From baseline to end of treatment (Visit 10, Week 24 or early termination) | Change in transforming growth factor beta-induced-protein (TGFBI) Fractional Synthesis Rate (FSR) from baseline to end of treatment evaluated through the use of deuterated water. TGFBI is a marker indicative of hepatic fibrogenesis with its turnover assessed by FSR. This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results were expressed as FSR of these proteins. |
| Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment | From baseline to end of treatment (Visit 10, Week 24 or early termination) | Percent Change in transforming growth factor beta-induced protein (TGFBI) FSR from baseline to end of treatment evaluated through the use of deuterated water. TGFBI is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results were expressed as FSR of these proteins. |
| Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan® | 24 weeks | FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The CAP score is a measurement of fatty change in the liver, naming the steatosis grade. The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m. 100 to 237 dB/M indicates no hepatic steatosis, 238 to 260 dB/m indicates mild hepatic steatosis (steatosis S1), 260 to 290 dB/m indicates moderate steatosis (steatosis S2), and a CAP score greater than 290 dB/m indicates severe steatosis (steatosis S3). |
| Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan® | 24 weeks | FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The CAP score is a measurement of fatty change in the liver, naming the steatosis grade.The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m. 100 to 237 dB/M indicates no hepatic steatosis, 238 to 260 dB/m indicates mild hepatic steatosis (steatosis S1), 260 to 290 dB/m indicates moderate steatosis (steatosis S2), and a CAP score greater than 290 dB/m indicates severe steatosis (steatosis S3). |
| Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan® | 24 weeks | FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa indicating the abscence of abscence of fibrosis (F0) or a potential fibrosis of stage 1 (F1). The highest possible result is 75 kPa indicating advanced liver fibrosis of stage 4 (F4). |
| Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan® | 24 weeks | FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa indicating the abscence of abscence of fibrosis (F0) or a potential fibrosis of stage 1 (F1). The highest possible result is 75 kPa indicating advanced liver fibrosis of stage 4 (F4). |
| Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | 12 weeks | Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit. |
| Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | 12 weeks | Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit. |
| Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | 24 weeks | Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit. |
| Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk. |
| Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk. |
| Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | 24 weeks | Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit. |
| Change in Alpha-2 Macroglobulin From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Alpha-2 Macroglobulin From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Fibroblast Growth Factor 19 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Fibroblast Growth Factor 21 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Human Chitinase 3-like 1 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Human Chitinase 3-like 1 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Human Chitinase 3-like 1 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Hyaluronic Acid From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Hyaluronic Acid From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Hyaluronic Acid From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Hyaluronic Acid From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk |
| Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk. |
| Change in M30 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in M30 Biomarker From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in M30 Biomarker From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in M30 Biomarker From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in M65 Biomarker From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in M65 Biomarker From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in M65 Biomarker From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in M65 Biomarker From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in miR34a Fold From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in miR34a Fold From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in miR34a Fold From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in miR34a Fold From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Pro-C3 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Pro-C3 From Baseline to Week 12 | 12 weeks | The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). |
| Change in Pro-C3 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Pro-C3 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Pro-C6 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Pro-C6 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Pro-C6 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12 | 12 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment | 24 weeks | Non-invasive Fibrosis Biomarkers were assessed in blood samples. |
| Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12 | 12 weeks | NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis. |
| Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12 | 12 weeks | NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis. |
| Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment | 24 weeks | NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis. |
| Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment | 24 weeks | NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis. |
| Change in Fibrosis-4 Score From Baseline to Week 12 | 12 weeks | Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6. |
| Percent Change in Fibrosis-4 Score From Baseline to Week 12 | 12 weeks | Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6. |
| Change in Fibrosis-4 Score From Baseline to End of Treatment | 24 weeks | Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6. |
| Percent Change in Fibrosis-4 Score From Baseline to End of Treatment | 24 weeks | Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6. |
Countries
United States
Participant flow
Recruitment details
Male and female patients aged from 18 to 75 years, inclusive, at the Screening Visit, with histologically confirmed NASH and fibrosis Stage 2 or 3 were enrolled in the study at a single research center in the United States, at Pinnacle Clinical Research, 5109 Medical Drive, Suite 200 San Antonio, TX 78229.
Pre-assignment details
Potential Subjects who completed all of the Screening Visit assessments and who continued to be eligible for the study, returned to the research center to complete a deuterated water Run-In period. The visit was done on Day -14 +/- 3 days, provided that the subject completed 7 consecutive days of deuterated water administration. Patients returned at Day-11, Day-7 (+/- 1 day) and Day 1 for blood sampling (labelled D2O).
Participants by arm
| Arm | Count |
|---|---|
| NTZ 500 mg BID Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | NTZ 500 mg BID |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 55.2 years STANDARD_DEVIATION 11.8 |
| Baseline body mass index | 34.64 kg/m² STANDARD_DEVIATION 4.638 |
| Baseline weight | 94.14 kg STANDARD_DEVIATION 17.793 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height at Screening | 164.4 cm STANDARD_DEVIATION 9.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 20 / 21 |
| serious Total, serious adverse events | 4 / 21 |
Outcome results
Primary
Deaths Due to AE
To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of deaths due to adverse events (AEs).
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Deaths Due to AE | Yes | 0 Participants |
| NTZ 500 mg BID | Deaths Due to AE | No | 21 Participants |
Primary
Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug
To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of adverse events (AEs) leading to withdrawal from study or study drug.
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug | At least one AE leading to withdrawal | 1 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug | No AE leading to withdrawal | 20 Participants |
Primary
Number of NTZ Treated Participants Presenting Any SAE
To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of serious adverse events (SAEs).
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any SAE | At least one SAE | 4 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any SAE | No SAE | 17 Participants |
Primary
Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug
To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related adverse events (AEs) leading to withdrawal from study or study drug
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug | At least one study drug-related AE leading to withdrawal | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug | No study drug-related AE leading to withdrawal | 21 Participants |
Primary
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE
To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related treatment-emergent adverse events (TEAEs).
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | No of participants with at least 1 treatment-related TEAE | 18 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | TEAE maximum severity: Grade 1 (mild) | 10 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | TEAE maximum severity: Grade 2 (moderate) | 8 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | TEAE maximum severity: Grade 3 (severe) | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | TEAE maximum severity: Grade 4 (life-threatening) | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | TEAE maximum severity: Grade 5 (death) | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE | No of participants with no study drug-related TEAE | 3 Participants |
Primary
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE)
To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of treatment-emergent adverse events (TEAEs).
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | No of participants with at least one TEAE | 20 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | TEAE maximum severity: Grade 1 (mild) | 7 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | TEAE maximum severity: Grade 2 (moderate) | 10 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | TEAE maximum severity: Grade 3 (severe) | 3 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | TEAE maximum severity: Grade 4 (life-threatening) | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | TEAE maximum severity: Grade 5 (death) | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) | No of participants with no TEAE | 1 Participants |
Primary
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations
To assess the safety and tolerability of NTZ after 24 weeks of treatment by performing clinical laboratory evaluations. Changes in clinical laboratory evaluations were considered clinically significant or not as per Investigator judgment.
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations | No CS change | 21 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations | At least one CS change | 0 Participants |
Primary
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters
To assess the safety and tolerability of NTZ after 24 weeks of treatment by performing electrocardiograms (ECGs). Changes in ECGs parameters were considered clinically significant or not as per Investigator judgement.
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters | At least one CS change | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters | No CS change | 21 Participants |
Primary
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations
To assess the safety and tolerability of NTZ after 24 weeks of treatment by conducting physical examinations. Changes in physical examinations were considered clinically significant or not as per Investigator judgement.
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations | At least one CS change | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations | No CS change | 21 Participants |
Primary
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs
To assess the safety and tolerability of NTZ after 24 weeks of treatment by measuring vital signs. Changes in vital signs were considered clinically significant or not as per Investigator judgement
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs | At least one CS change | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs | No CS change | 21 Participants |
Primary
Number of NTZ Treated Participants Presenting Study Drug-Related SAE
To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related serious adverse events (SAEs).
Time frame: 28 weeks
Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Study Drug-Related SAE | At least one study-drug related SAE | 0 Participants |
| NTZ 500 mg BID | Number of NTZ Treated Participants Presenting Study Drug-Related SAE | No study-drug related SAE | 21 Participants |
Secondary
Change in Alpha-2 Macroglobulin From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Alpha-2 Macroglobulin From Baseline to End of Treatment | -9.0 mg/dL |
p-value: 0.330695% CI: [-21.2, 7.6]t-test, 2 sided
Secondary
Change in Alpha-2 Macroglobulin From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Alpha-2 Macroglobulin From Baseline to Week 12 | -11.0 mg/dL |
p-value: 0.070995% CI: [-30.6, 1.4]t-test, 2 sided
Secondary
Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®
FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The CAP score is a measurement of fatty change in the liver, naming the steatosis grade. The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m. 100 to 237 dB/M indicates no hepatic steatosis, 238 to 260 dB/m indicates mild hepatic steatosis (steatosis S1), 260 to 290 dB/m indicates moderate steatosis (steatosis S2), and a CAP score greater than 290 dB/m indicates severe steatosis (steatosis S3).
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan® | -8.1 dB/m | Standard Deviation 44.59 |
p-value: 0.463895% CI: [-31, 14.8]t-test, 2 sided
Secondary
Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment | 24.0 ng/L |
p-value: 0.428195% CI: [-50.3, 112.9]t-test, 2 sided
Secondary
Change in Fibroblast Growth Factor 19 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Fibroblast Growth Factor 19 From Baseline to Week 12 | 28.0 ng/L |
p-value: 0.134995% CI: [-11.5, 79]t-test, 2 sided
Secondary
Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment | -102.90 ng/L |
p-value: 0.709995% CI: [-317.64, 221.36]t-test, 2 sided
Secondary
Change in Fibroblast Growth Factor 21 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Fibroblast Growth Factor 21 From Baseline to Week 12 | 2.40 ng/L |
p-value: 0.706595% CI: [-210.9, 305.46]t-test, 2 sided
Secondary
Change in Fibrosis-4 Score From Baseline to End of Treatment
Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Fibrosis-4 Score From Baseline to End of Treatment | -0.12 score | Standard Deviation 0.328 |
p-value: 0.317495% CI: [-0.4, 0.15]t-test, 2 sided
Secondary
Change in Fibrosis-4 Score From Baseline to Week 12
Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Fibrosis-4 Score From Baseline to Week 12 | -0.18 score | Standard Deviation 0.516 |
p-value: 0.145895% CI: [-0.42, 0.07]t-test, 2 sided
Secondary
Change in Human Chitinase 3-like 1 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Human Chitinase 3-like 1 From Baseline to End of Treatment | 5338.0 ng/L |
p-value: 0.808995% CI: [-22996.2, 29029.7]t-test, 2 sided
Secondary
Change in Human Chitinase 3-like 1 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Human Chitinase 3-like 1 From Baseline to Week 12 | 5423.0 ng/L |
p-value: 0.989395% CI: [-25908.2, 26246.2]t-test, 2 sided
Secondary
Change in Hyaluronic Acid From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Hyaluronic Acid From Baseline to End of Treatment | 6.100 µg/L |
p-value: 0.083195% CI: [-4.151, 60.774]t-test, 2 sided
Secondary
Change in Hyaluronic Acid From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Hyaluronic Acid From Baseline to Week 12 | 6.210 µg/L |
p-value: 0.132295% CI: [-9.525, 67.433]t-test, 2 sided
Secondary
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment | 0.090 score |
p-value: 0.273395% CI: [-0.14, 0.462]t-test, 2 sided
Secondary
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12 | -0.160 score |
p-value: 0.632595% CI: [-0.185, 0.298]t-test, 2 sided
Secondary
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®
FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa indicating the abscence of abscence of fibrosis (F0) or a potential fibrosis of stage 1 (F1). The highest possible result is 75 kPa indicating advanced liver fibrosis of stage 4 (F4).
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan® | 0.38 kPa | Standard Deviation 4.341 |
p-value: 0.725495% CI: [-1.86, 2.61]t-test, 2 sided
Secondary
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 12 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | -0.35 kPa | Standard Deviation 0.581 |
p-value: 0.060995% CI: [-0.72, 0.02]t-test, 2 sided
Secondary
Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 13 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | -0.12 kPa | Standard Deviation 0.731 |
p-value: 0.579995% CI: [-0.56, 0.33]t-test, 2 sided
Secondary
Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment
Change in Lumican Fractional Synthesis Rate (FSR) from baseline to end of treatment evaluated through the use of deuterated water. Lumican is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein.
Time frame: From baseline to end of treatment (Visit 10, Week 24 or early termination)
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment | 0.0046 pools per day | Standard Deviation 0.00924 |
p-value: 0.0039Sign test
Secondary
Change in M30 Biomarker From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in M30 Biomarker From Baseline to End of Treatment | -34.920 U/L |
p-value: 0.728895% CI: [-211.93, 151.441]t-test, 2 sided
Secondary
Change in M30 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in M30 From Baseline to Week 12 | 0.000 U/L |
p-value: 0.927195% CI: [-121.923, 133.22]t-test, 2 sided
Secondary
Change in M65 Biomarker From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in M65 Biomarker From Baseline to End of Treatment | -58.970 U/L |
p-value: 0.325695% CI: [-351.124, 123.891]t-test, 2 sided
Secondary
Change in M65 Biomarker From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in M65 Biomarker From Baseline to Week 12 | -15.605 U/L |
p-value: 0.644895% CI: [-260.433, 165.176]t-test, 2 sided
Secondary
Change in miR34a Fold From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in miR34a Fold From Baseline to End of Treatment | -0.5019 fold change |
p-value: 0.488795% CI: [-1.158, 0.5794]t-test, 2 sided
Secondary
Change in miR34a Fold From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in miR34a Fold From Baseline to Week 12 | -0.0991 fold change |
p-value: 0.545995% CI: [-1.0847, 0.5972]t-test, 2 sided
Secondary
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment
NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment | -0.2679 score | Standard Deviation 0.43795 |
p-value: 0.127295% CI: [-0.634, 0.0983]t-test, 2 sided
Secondary
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12
NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12 | -0.3665 score | Standard Deviation 0.77812 |
p-value: 0.048795% CI: [-0.7306, -0.0023]t-test, 2 sided
Secondary
Change in Pro-C3 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Pro-C3 From Baseline to End of Treatment | -2.60 µg/L |
p-value: 0.024395% CI: [-5.96, -0.47]t-test, 2 sided
Secondary
Change in Pro-C3 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Pro-C3 From Baseline to Week 12 | -0.80 µg/L |
p-value: 0.494595% CI: [-2.51, 1.26]t-test, 2 sided
Secondary
Change in Pro-C6 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Pro-C6 From Baseline to End of Treatment | -0.20 µg/L |
p-value: 0.824195% CI: [-0.94, 1.16]t-test, 2 sided
Secondary
Change in Pro-C6 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Pro-C6 From Baseline to Week 12 | 0.40 µg/L |
p-value: 0.306695% CI: [-0.59, 1.79]t-test, 2 sided
Secondary
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment | 0.180 µg/L |
p-value: 0.921895% CI: [-1.978, 2.173]t-test, 2 sided
Secondary
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12 | -1.560 µg/L |
p-value: 0.378495% CI: [-1.88, 0.746]t-test, 2 sided
Secondary
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment | 13.40 µg/L |
p-value: 0.060795% CI: [-0.77, 31.21]t-test, 2 sided
Secondary
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12 | 10.50 µg/L |
p-value: 0.395795% CI: [-17.79, 43.16]t-test, 2 sided
Secondary
Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment
Change in transforming growth factor beta-induced-protein (TGFBI) Fractional Synthesis Rate (FSR) from baseline to end of treatment evaluated through the use of deuterated water. TGFBI is a marker indicative of hepatic fibrogenesis with its turnover assessed by FSR. This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results were expressed as FSR of these proteins.
Time frame: From baseline to end of treatment (Visit 10, Week 24 or early termination)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment | 0.0014 pools per day | Standard Deviation 0.01124 |
p-value: 0.5555Sign test
Secondary
Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment | -4.85 percentage of change |
p-value: 0.450495% CI: [-7.25, 3.37]t-test, 2 sided
Secondary
Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12 | -5.64 percentage of change |
p-value: 0.179995% CI: [-9.02, 1.81]t-test, 2 sided
Secondary
Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®
FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The CAP score is a measurement of fatty change in the liver, naming the steatosis grade.The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m. 100 to 237 dB/M indicates no hepatic steatosis, 238 to 260 dB/m indicates mild hepatic steatosis (steatosis S1), 260 to 290 dB/m indicates moderate steatosis (steatosis S2), and a CAP score greater than 290 dB/m indicates severe steatosis (steatosis S3).
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan® | -1.65 percentage of change | Standard Deviation 14.818 |
p-value: 0.653295% CI: [-9.26, 5.97]t-test, 2 sided
Secondary
Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment | 42.11 percentage of change |
p-value: 0.040795% CI: [5.6, 229.14]t-test, 2 sided
Secondary
Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 12 | 38.74 percentage of change |
p-value: 0.011795% CI: [19.04, 133.43]t-test, 2 sided
Secondary
Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment | -15.36 percentage of change |
p-value: 0.359795% CI: [-37.48, 97.55]t-test, 2 sided
Secondary
Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 12 | 0.36 percentage of change |
p-value: 0.169395% CI: [-19.95, 106.17]t-test, 2 sided
Secondary
Percent Change in Fibrosis-4 Score From Baseline to End of Treatment
Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Fibrosis-4 Score From Baseline to End of Treatment | -8.02 percentage of change | Standard Deviation 17.754 |
p-value: 0.24295% CI: [-22.86, 6.82]t-test, 2 sided
Secondary
Percent Change in Fibrosis-4 Score From Baseline to Week 12
Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Fibrosis-4 Score From Baseline to Week 12 | -11.53 percentage of change | Standard Deviation 34.342 |
p-value: 0.149595% CI: [-27.61, 4.54]t-test, 2 sided
Secondary
Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment | 8.76 percentage of change |
p-value: 0.136595% CI: [-4.5, 30.06]t-test, 2 sided
Secondary
Percent Change in Human Chitinase 3-like 1 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Human Chitinase 3-like 1 From Baseline to Week 12 | 8.90 percentage of change |
p-value: 0.145495% CI: [-5.21, 32.85]t-test, 2 sided
Secondary
Percent Change in Hyaluronic Acid From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Hyaluronic Acid From Baseline to End of Treatment | 6.99 percentage of change |
p-value: 0.054395% CI: [-0.69, 66.13]t-test, 2 sided
Secondary
Percent Change in Hyaluronic Acid From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Hyaluronic Acid From Baseline to Week 12 | 10.93 percentage of change |
p-value: 0.106295% CI: [-5.59, 53.57]t-test, 2 sided
Secondary
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment | 0.90 percentage of change |
p-value: 0.328895% CI: [-1.63, 4.56]t-test, 2 sided
Secondary
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12 | -1.64 percentage of change |
p-value: 0.692595% CI: [-1.94, 2.87]t-test, 2 sided
Secondary
Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®
FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa indicating the abscence of abscence of fibrosis (F0) or a potential fibrosis of stage 1 (F1). The highest possible result is 75 kPa indicating advanced liver fibrosis of stage 4 (F4).
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan® | 8.77 percentage of change | Standard Deviation 39.828 |
p-value: 0.377295% CI: [-11.7, 29.25]t-test, 2 sided
Secondary
Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 12 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | -6.61 percentage of change | Standard Deviation 15.029 |
p-value: 0.155695% CI: [-16.16, 2.94]t-test, 2 sided
Secondary
Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 13 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE) | -1.89 percentage of change | Standard Deviation 17.807 |
p-value: 0.708895% CI: [-12.65, 8.87]t-test, 2 sided
Secondary
Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment
Percent Change in Lumican FSR from baseline to end of treatment evaluated through the use of deuterated water. Lumican is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein.
Time frame: From baseline to end of treatment (Visit 10, Week 24 or early termination)
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment | 15.46 percentage of change | Standard Deviation 22.507 |
p-value: 0.0026Sign test
Secondary
Percent Change in M30 Biomarker From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in M30 Biomarker From Baseline to End of Treatment | -5.48 percentage of change |
p-value: 0.782495% CI: [-21.85, 28.52]t-test, 2 sided
Secondary
Percent Change in M30 Biomarker From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in M30 Biomarker From Baseline to Week 12 | 0.00 percentage of change |
p-value: 0.924495% CI: [-18.58, 20.37]t-test, 2 sided
Secondary
Percent Change in M65 Biomarker From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in M65 Biomarker From Baseline to End of Treatment | -11.56 percentage of change |
p-value: 0.658295% CI: [-32.52, 50.09]t-test, 2 sided
Secondary
Percent Change in M65 Biomarker From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in M65 Biomarker From Baseline to Week 12 | -3.52 percentage of change |
p-value: 0.980695% CI: [-32.04, 32.8]t-test, 2 sided
Secondary
Percent Change in miR34a Fold From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in miR34a Fold From Baseline to End of Treatment | -24.90 percentage of change |
p-value: 0.36195% CI: [-38.21, 98.75]t-test, 2 sided
Secondary
Percent Change in miR34a Fold From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in miR34a Fold From Baseline to Week 12 | -7.42 percentage of change |
p-value: 0.28695% CI: [-22.15, 69.97]t-test, 2 sided
Secondary
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment
NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment | 15.02 percentage of change | Standard Deviation 74.847 |
p-value: 0.588195% CI: [-47.55, 77.59]t-test, 2 sided
Secondary
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12
NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12 | 16.64 percentage of change | Standard Deviation 136.529 |
p-value: 0.591995% CI: [-47.25, 80.54]t-test, 2 sided
Secondary
Percent Change in Pro-C3 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Pro-C3 From Baseline to End of Treatment | -12.70 percentage of change |
p-value: 0.049395% CI: [-19.84, -0.04]t-test, 2 sided
Secondary
Percent Change in Pro-C3 From Baseline to Week 12
The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Pro-C3 From Baseline to Week 12 | -2.80 percentage of change |
p-value: 0.819195% CI: [-9.94, 7.95]t-test, 2 sided
Secondary
Percent Change in Pro-C6 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Pro-C6 From Baseline to End of Treatment | -0.75 percentage of change |
p-value: 0.758795% CI: [-6.37, 8.57]t-test, 2 sided
Secondary
Percent Change in Pro-C6 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Pro-C6 From Baseline to Week 12 | 1.98 percentage of change |
p-value: 0.267195% CI: [-2.82, 9.63]t-test, 2 sided
Secondary
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment | 1.22 percentage of change |
p-value: 0.983395% CI: [-14.71, 15.01]t-test, 2 sided
Secondary
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12 | -9.73 percentage of change |
p-value: 0.352695% CI: [-14.8, 5.53]t-test, 2 sided
Secondary
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 24 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment | 3.78 percentage of change |
p-value: 0.064495% CI: [-0.39, 12.05]t-test, 2 sided
Secondary
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12
Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time frame: 12 weeks
Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).~21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NTZ 500 mg BID | Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12 | 3.53 percentage of change |
p-value: 0.34495% CI: [-4.39, 12.01]t-test, 2 sided
Secondary
Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment
Percent Change in transforming growth factor beta-induced protein (TGFBI) FSR from baseline to end of treatment evaluated through the use of deuterated water. TGFBI is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given heavy water to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results were expressed as FSR of these proteins.
Time frame: From baseline to end of treatment (Visit 10, Week 24 or early termination)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTZ 500 mg BID | Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment | 3.20 percentage of change | Standard Deviation 12.619 |
p-value: 0.3778Sign test