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CompletedNCT03656068Updated Jun 30, 2022Results posted

An Evaluation of the Safety and Efficacy of Nitazoxanide on Collagen Turnover in NASH Patients With Fibrosis

A Phase 2 interventional study of Nitazoxanide 500mg BID in Non-alcoholic Steatohepatitis, Fatty Liver and Fibrosis, Liver, sponsored by Pinnacle Clinical Research, PLLC. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2022-06-30.

Sponsored by Pinnacle Clinical Research, PLLC · Phase 2, Interventional, and Basic science

Phase
Phase 2
Study type
Interventional
Enrollment
21
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study 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

Read the 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®.

02

Conditions studied

  • Non-alcoholic Steatohepatitis
  • Fatty Liver
  • Fibrosis, Liver
  • Compensated Cirrhosis
03

In context

Fatty Liver

1,451 studies on the registry are indexed under Fatty Liver; 292 are open to participants now.

This study's enrollment of 21 is below the median of 60 across 1,003 interventional studies indexed under Fatty Liver.

Browse Fatty Liver studies →

Lead sponsor

This is the only study on the registry with Pinnacle Clinical Research, PLLC as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts 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

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).
05

Study design

Phase
Phase 2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    Open label NTZ

    Open label. All patients will receive study drug

    Drug: Nitazoxanide 500mg BID

Interventions

  • DrugNitazoxanide 500mg BID

    Patients will receive 500mg of Nitazoxanide BID daily for 24 weeks

    Also known as: NTZ

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Change in Alpha-2 Macroglobulin From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  14. Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  15. Change in Alpha-2 Macroglobulin From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  16. 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

  17. Change in Fibroblast Growth Factor 19 From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  18. 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

  19. 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

  20. 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

  21. Change in Fibroblast Growth Factor 21 From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. Change in Hyaluronic Acid From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  30. Percent Change in Hyaluronic Acid From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  31. Change in Hyaluronic Acid From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  32. Percent Change in Hyaluronic Acid From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  33. 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

  34. 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

  35. 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

  36. 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

  37. Change in M30 From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  38. Percent Change in M30 Biomarker From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  39. Change in M30 Biomarker From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  40. Percent Change in M30 Biomarker From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  41. Change in M65 Biomarker From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  42. Percent Change in M65 Biomarker From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  43. Change in M65 Biomarker From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  44. Percent Change in M65 Biomarker From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  45. Change in miR34a Fold From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  46. Percent Change in miR34a Fold From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  47. Change in miR34a Fold From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  48. Percent Change in miR34a Fold From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  49. Change in Pro-C3 From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  50. 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

  51. Change in Pro-C3 From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  52. Percent Change in Pro-C3 From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  53. Change in Pro-C6 From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  54. Percent Change in Pro-C6 From Baseline to Week 12

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 12 weeks

  55. Change in Pro-C6 From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  56. Percent Change in Pro-C6 From Baseline to End of Treatment

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

    Time frame: 24 weeks

  57. 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

  58. 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

  59. 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

  60. 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

  61. 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

  62. 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

  63. 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

  64. 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

  65. 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

  66. 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

  67. 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

  68. 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

  69. 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

  70. 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

  71. 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

  72. 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

07

Results

Posted Jun 30, 2022

Participant flow

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.

Participant flow — Overall Study
MilestoneNTZ 500 mg BID
Started21
Completed16
Not completed5
Withdrew: Withdrawal by subject4
Withdrew: Adverse event1

Outcome measures

PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE)
ParticipantsNTZ 500 mg BID
No of participants with at least one TEAE20
TEAE maximum severity: Grade 1 (mild)7
TEAE maximum severity: Grade 2 (moderate)10
TEAE maximum severity: Grade 3 (severe)3
TEAE maximum severity: Grade 4 (life-threatening)0
TEAE maximum severity: Grade 5 (death)0
No of participants with no TEAE1
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE
ParticipantsNTZ 500 mg BID
No of participants with at least 1 treatment-related TEAE18
TEAE maximum severity: Grade 1 (mild)10
TEAE maximum severity: Grade 2 (moderate)8
TEAE maximum severity: Grade 3 (severe)0
TEAE maximum severity: Grade 4 (life-threatening)0
TEAE maximum severity: Grade 5 (death)0
No of participants with no study drug-related TEAE3
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting Any SAE
ParticipantsNTZ 500 mg BID
At least one SAE4
No SAE17
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting Study Drug-Related SAE
ParticipantsNTZ 500 mg BID
At least one study-drug related SAE0
No study-drug related SAE21
PrimaryDeaths 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
Reported as:
Count of participants · Participants
Deaths Due to AE
ParticipantsNTZ 500 mg BID
Yes0
No21
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug
ParticipantsNTZ 500 mg BID
At least one AE leading to withdrawal1
No AE leading to withdrawal20
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug
ParticipantsNTZ 500 mg BID
At least one study drug-related AE leading to withdrawal0
No study drug-related AE leading to withdrawal21
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations
ParticipantsNTZ 500 mg BID
At least one CS change0
No CS change21
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs
ParticipantsNTZ 500 mg BID
At least one CS change0
No CS change21
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters
ParticipantsNTZ 500 mg BID
At least one CS change0
No CS change21
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations
ParticipantsNTZ 500 mg BID
At least one CS change0
No CS change21
SecondaryChange 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)
Reported as:
Mean · pools per day
Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment
pools per dayNTZ 500 mg BID
Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment0.0046 ± 0.00924
Statistical analysis
  • NTZ 500 mg BID · Sign test · p = 0.0039 (p-value for testing median = 0) · Median difference (net): 0.0030
SecondaryPercent 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)
Reported as:
Mean · percentage of change
Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment15.46 ± 22.507
Statistical analysis
  • NTZ 500 mg BID · Sign test · p = 0.0026 (p-value for testing median = 0) · Median difference (net): 10.00
SecondaryChange 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)
Reported as:
Mean · pools per day
Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment
pools per dayNTZ 500 mg BID
Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment0.0014 ± 0.01124
Statistical analysis
  • NTZ 500 mg BID · Sign test · p = 0.5555 (p-value for testing median = 0) · Median difference (net): 0.0020
SecondaryPercent 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)
Reported as:
Mean · percentage of change
Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment3.20 ± 12.619
Statistical analysis
  • NTZ 500 mg BID · Sign test · p = 0.3778 (p-value for testing median = 0) · Median difference (net): 1.72
SecondaryChange 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
Reported as:
Mean · dB/m
Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®
dB/mNTZ 500 mg BID
Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®-8.1 ± 44.59
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.4638 (p-value for testing mean = 0) · Mean difference (net): -8.1 · 95% CI -31.0 to 14.8
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®
percentage of changeNTZ 500 mg BID
Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®-1.65 ± 14.818
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.6532 (p-value for testing mean = 0) · Mean difference (net): -1.65 · 95% CI -9.26 to 5.97
SecondaryChange 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
Reported as:
Mean · kPa
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®
kPaNTZ 500 mg BID
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®0.38 ± 4.341
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.7254 (p-value for testing mean = 0) · Mean difference (net): 0.38 · 95% CI -1.86 to 2.61
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®
percentage of changeNTZ 500 mg BID
Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®8.77 ± 39.828
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3772 (p-value for testing mean = 0) · Mean difference (net): 8.77 · 95% CI -11.70 to 29.25
SecondaryChange 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
Reported as:
Mean · kPa
Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
kPaNTZ 500 mg BID
Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)-0.12 ± 0.731
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.5799 (p-value for testing mean = 0) · Mean difference (net): -0.12 · 95% CI -0.56 to 0.33
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
percentage of changeNTZ 500 mg BID
Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)-1.89 ± 17.807
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.7088 (p-value for testing mean = 0) · Mean difference (net): -1.89 · 95% CI -12.65 to 8.87
SecondaryChange 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
Reported as:
Mean · kPa
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
kPaNTZ 500 mg BID
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)-0.35 ± 0.581
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0609 (p-value for testing mean = 0) · Mean difference (net): -0.35 · 95% CI -0.72 to 0.02
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
percentage of changeNTZ 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 ± 15.029
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1556 (p-value for testing mean = 0) · Mean difference (net): -6.61 · 95% CI -16.16 to 2.94
SecondaryChange in Alpha-2 Macroglobulin From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · mg/dL
Change in Alpha-2 Macroglobulin From Baseline to Week 12
mg/dLNTZ 500 mg BID
Change in Alpha-2 Macroglobulin From Baseline to Week 12-11.0 (-94 to 56)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0709 (p-value for testing mean = 0) · Mean difference (net): -14.6 · 95% CI -30.6 to 1.4
SecondaryPercent Change in Alpha-2 Macroglobulin From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12-5.64 (-20.0 to 27.3)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1799 (p-value for testing mean = 0) · Mean difference (net): -3.61 · 95% CI -9.02 to 1.81
SecondaryChange in Alpha-2 Macroglobulin From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · mg/dL
Change in Alpha-2 Macroglobulin From Baseline to End of Treatment
mg/dLNTZ 500 mg BID
Change in Alpha-2 Macroglobulin From Baseline to End of Treatment-9.0 (-70 to 42)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3306 (p-value for testing mean = 0) · Mean difference (net): -6.8 · 95% CI -21.2 to 7.6
SecondaryPercent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · percentage of change
Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment-4.85 (-16.0 to 22.6)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.4504 (p-value for testing mean = 0) · Mean difference (net): -1.94 · 95% CI -7.25 to 3.37
SecondaryChange in Fibroblast Growth Factor 19 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · ng/L
Change in Fibroblast Growth Factor 19 From Baseline to Week 12
ng/LNTZ 500 mg BID
Change in Fibroblast Growth Factor 19 From Baseline to Week 1228.0 (-155 to 282)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1349 (p-value for testing mean = 0) · Mean difference (net): 33.8 · 95% CI -11.5 to 79.0
SecondaryPercent Change in Fibroblast Growth Factor 19 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 1238.74 (-68.9 to 361.1)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0117 (p-value for testing mean = 0) · Mean difference (net): 76.24 · 95% CI 19.04 to 133.43
SecondaryChange in Fibroblast Growth Factor 19 From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · ng/L
Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment
ng/LNTZ 500 mg BID
Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment24.0 (-377 to 290)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.4281 (p-value for testing mean = 0) · Mean difference (net): 31.3 · 95% CI -50.3 to 112.9
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment42.11 (-81.1 to 637.8)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0407 (p-value for testing mean = 0) · Mean difference (net): 117.37 · 95% CI 5.60 to 229.14
SecondaryChange in Fibroblast Growth Factor 21 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · ng/L
Change in Fibroblast Growth Factor 21 From Baseline to Week 12
ng/LNTZ 500 mg BID
Change in Fibroblast Growth Factor 21 From Baseline to Week 122.40 (-1609.8 to 1009.8)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.7065 (p-value for testing mean = 0) · Mean difference (net): 47.28 · 95% CI -210.90 to 305.46
SecondaryPercent Change in Fibroblast Growth Factor 21 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 120.36 (-68.6 to 504.6)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1693 (p-value for testing mean = 0) · Mean difference (net): 43.11 · 95% CI -19.95 to 106.17
SecondaryChange in Fibroblast Growth Factor 21 From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · ng/L
Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment
ng/LNTZ 500 mg BID
Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment-102.90 (-1728.6 to 928.9)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.7099 (p-value for testing mean = 0) · Mean difference (net): -48.14 · 95% CI -317.64 to 221.36
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment-15.36 (-56.8 to 511.8)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3597 (p-value for testing mean = 0) · Mean difference (net): 30.03 · 95% CI -37.48 to 97.55
SecondaryChange in Human Chitinase 3-like 1 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · ng/L
Change in Human Chitinase 3-like 1 From Baseline to Week 12
ng/LNTZ 500 mg BID
Change in Human Chitinase 3-like 1 From Baseline to Week 125423.0 (-180529 to 91341)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.9893 (p-value for testing mean = 0) · Mean difference (net): 169.0 · 95% CI -25908.2 to 26246.2
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Human Chitinase 3-like 1 From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Human Chitinase 3-like 1 From Baseline to Week 128.90 (-54.0 to 106.6)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1454 (p-value for testing mean = 0) · Mean difference (net): 13.82 · 95% CI -5.21 to 32.85
SecondaryChange 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
Reported as:
Median · ng/L
Change in Human Chitinase 3-like 1 From Baseline to End of Treatment
ng/LNTZ 500 mg BID
Change in Human Chitinase 3-like 1 From Baseline to End of Treatment5338.0 (-102066 to 121135)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.8089 (p-value for testing mean = 0) · Mean difference (net): 3016.8 · 95% CI -22996.2 to 29029.7
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment8.76 (-36.8 to 74.9)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1365 (p-value for testing mean = 0) · Mean difference (net): 12.78 · 95% CI -4.50 to 30.06
SecondaryChange in Hyaluronic Acid From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · µg/L
Change in Hyaluronic Acid From Baseline to Week 12
µg/LNTZ 500 mg BID
Change in Hyaluronic Acid From Baseline to Week 126.210 (-22.12 to 323.24)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1322 (p-value for testing mean = 0) · Mean difference (net): 28.954 · 95% CI -9.525 to 67.433
SecondaryPercent Change in Hyaluronic Acid From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in Hyaluronic Acid From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Hyaluronic Acid From Baseline to Week 1210.93 (-41.1 to 199.3)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1062 · Mean difference (net): 23.99 · 95% CI -5.59 to 53.57p-value for testing mean = 0
SecondaryChange in Hyaluronic Acid From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · µg/L
Change in Hyaluronic Acid From Baseline to End of Treatment
µg/LNTZ 500 mg BID
Change in Hyaluronic Acid From Baseline to End of Treatment6.100 (-26.83 to 235.19)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0831 (p-value for testing mean = 0) · Mean difference (net): 28.311 · 95% CI -4.151 to 60.774
SecondaryPercent Change in Hyaluronic Acid From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · percentage of change
Percent Change in Hyaluronic Acid From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Hyaluronic Acid From Baseline to End of Treatment6.99 (-46.2 to 202.2)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0543 (p-value for testing mean = 0) · Mean difference (net): 32.72 · 95% CI -0.69 to 66.13
SecondaryChange 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
Reported as:
Median · score
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12
scoreNTZ 500 mg BID
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12-0.160 (-0.67 to 1.25)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.6325 (p-value for testing mean = 0) · Mean difference (net): 0.056 · 95% CI -0.185 to 0.298
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12-1.64 (-7.3 to 11.5)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.6925 (p-value for testing mean = 0) · Mean difference (net): 0.46 · 95% CI -1.94 to 2.87
SecondaryChange 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
Reported as:
Median · score
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment
scoreNTZ 500 mg BID
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment0.090 (-0.89 to 1.32)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.2733 · Mean difference (net): 0.161 · 95% CI -0.140 to 0.462
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment0.90 (-9.7 to 12.0)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3288 (p-value for testing mean = 0) · Mean difference (net): 1.47 · 95% CI -1.63 to 4.56
SecondaryChange in M30 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · U/L
Change in M30 From Baseline to Week 12
U/LNTZ 500 mg BID
Change in M30 From Baseline to Week 120.000 (-500.92 to 740.29)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.9271 (p-value for testing mean = 0) · Mean difference (net): 5.649 · 95% CI -121.923 to 133.220
SecondaryPercent Change in M30 Biomarker From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in M30 Biomarker From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in M30 Biomarker From Baseline to Week 120.00 (-59.7 to 89.2)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.9244 (p-value for testing mean = 0) · Mean difference (net): 0.89 · 95% CI -18.58 to 20.37
SecondaryChange in M30 Biomarker From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · U/L
Change in M30 Biomarker From Baseline to End of Treatment
U/LNTZ 500 mg BID
Change in M30 Biomarker From Baseline to End of Treatment-34.920 (-602.50 to 853.74)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.7288 (p-value for testing mean = 0) · Mean difference (net): -30.244 · 95% CI -211.930 to 151.441
SecondaryPercent Change in M30 Biomarker From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · percentage of change
Percent Change in M30 Biomarker From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in M30 Biomarker From Baseline to End of Treatment-5.48 (-63.9 to 113.0)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.7824 (p-value for testing mean = 0) · Mean difference (net): 3.34 · 95% CI -21.85 to 28.52
SecondaryChange in M65 Biomarker From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · U/L
Change in M65 Biomarker From Baseline to Week 12
U/LNTZ 500 mg BID
Change in M65 Biomarker From Baseline to Week 12-15.605 (-1100.35 to 801.43)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.6448 (p-value for testing mean = 0) · Mean difference (net): -47.629 · 95% CI -260.433 to 165.176
SecondaryPercent Change in M65 Biomarker From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in M65 Biomarker From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in M65 Biomarker From Baseline to Week 12-3.52 (-90.7 to 144.2)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.9806 (p-value for testing mean = 0) · Mean difference (net): 0.38 · 95% CI -32.04 to 32.80
SecondaryChange in M65 Biomarker From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · U/L
Change in M65 Biomarker From Baseline to End of Treatment
U/LNTZ 500 mg BID
Change in M65 Biomarker From Baseline to End of Treatment-58.970 (-1098.60 to 839.44)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3256 (p-value for testing mean = 0) · Mean difference (net): -113.616 · 95% CI -351.124 to 123.891
SecondaryPercent Change in M65 Biomarker From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · percentage of change
Percent Change in M65 Biomarker From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in M65 Biomarker From Baseline to End of Treatment-11.56 (-84.6 to 213.2)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.6582 (p-value for testing mean = 0) · Mean difference (net): 8.78 · 95% CI -32.52 to 50.09
SecondaryChange in miR34a Fold From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · fold change
Change in miR34a Fold From Baseline to Week 12
fold changeNTZ 500 mg BID
Change in miR34a Fold From Baseline to Week 12-0.0991 (-4.331 to 2.033)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.5459 (p-value for testing mean = 0) · Mean difference (net): -0.2438 · 95% CI -1.0847 to 0.5972
SecondaryPercent Change in miR34a Fold From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in miR34a Fold From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in miR34a Fold From Baseline to Week 12-7.42 (-66.3 to 213.8)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.2860 · Mean difference (net): 23.91 · 95% CI -22.15 to 69.97
SecondaryChange in miR34a Fold From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · fold change
Change in miR34a Fold From Baseline to End of Treatment
fold changeNTZ 500 mg BID
Change in miR34a Fold From Baseline to End of Treatment-0.5019 (-3.561 to 3.181)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.4887 (p-value for testing mean = 0) · Mean difference (net): -0.2893 · 95% CI -1.1580 to 0.5794
SecondaryPercent Change in miR34a Fold From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · percentage of change
Percent Change in miR34a Fold From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in miR34a Fold From Baseline to End of Treatment-24.90 (-78.1 to 308.4)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3610 (p-value for testing mean = 0) · Mean difference (net): 30.27 · 95% CI -38.21 to 98.75
SecondaryChange in Pro-C3 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · µg/L
Change in Pro-C3 From Baseline to Week 12
µg/LNTZ 500 mg BID
Change in Pro-C3 From Baseline to Week 12-0.80 (-8.0 to 10.8)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.4945 (p-value for testing mean = 0) · Mean difference (net): -0.63 · 95% CI -2.51 to 1.26
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Pro-C3 From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Pro-C3 From Baseline to Week 12-2.80 (-28.7 to 59.3)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.8191 (p-value for testing mean = 0) · Mean difference (net): -0.99 · 95% CI -9.94 to 7.95
SecondaryChange in Pro-C3 From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · µg/L
Change in Pro-C3 From Baseline to End of Treatment
µg/LNTZ 500 mg BID
Change in Pro-C3 From Baseline to End of Treatment-2.60 (-14.8 to 6.3)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0243 (p-value for testing mean = 0) · Mean difference (net): -3.22 · 95% CI -5.96 to -0.47
SecondaryPercent Change in Pro-C3 From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · percentage of change
Percent Change in Pro-C3 From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Pro-C3 From Baseline to End of Treatment-12.70 (-42.5 to 34.6)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0493 (p-value for testing mean = 0) · Mean difference (net): -9.94 · 95% CI -19.84 to -0.04
SecondaryChange in Pro-C6 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · µg/L
Change in Pro-C6 From Baseline to Week 12
µg/LNTZ 500 mg BID
Change in Pro-C6 From Baseline to Week 120.40 (-2.6 to 9.6)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3066 (p-value for testing mean = 0) · Mean difference (net): 0.60 · 95% CI -0.59 to 1.79
SecondaryPercent Change in Pro-C6 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · percentage of change
Percent Change in Pro-C6 From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Pro-C6 From Baseline to Week 121.98 (-14.4 to 36.2)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.2671 (p-value for testing mean = 0) · Mean difference (net): 3.40 · 95% CI -2.82 to 9.63
SecondaryChange in Pro-C6 From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · µg/L
Change in Pro-C6 From Baseline to End of Treatment
µg/LNTZ 500 mg BID
Change in Pro-C6 From Baseline to End of Treatment-0.20 (-4.4 to 3.9)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.8241 (p-value for testing mean = 0) · Mean difference (net): 0.11 · 95% CI -0.94 to 1.16
SecondaryPercent Change in Pro-C6 From Baseline to End of Treatment

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
24 weeks
Reported as:
Median · percentage of change
Percent Change in Pro-C6 From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Pro-C6 From Baseline to End of Treatment-0.75 (-24.3 to 24.5)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.7587 (p-value for testing mean = 0) · Mean difference (net): 1.10 · 95% CI -6.37 to 8.57
SecondaryChange 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
Reported as:
Median · µg/L
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12
µg/LNTZ 500 mg BID
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12-1.560 (-4.46 to 5.38)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3784 (p-value for testing mean = 0) · Mean difference (net): -0.567 · 95% CI -1.880 to 0.746
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12-9.73 (-33.5 to 34.9)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3526 (p-value for testing mean = 0) · Mean difference (net): -4.64 · 95% CI -14.80 to 5.53
SecondaryChange 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
Reported as:
Median · µg/L
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment
µg/LNTZ 500 mg BID
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment0.180 (-5.22 to 11.83)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.9218 (p-value for testing mean = 0) · Mean difference (net): 0.098 · 95% CI -1.978 to 2.173
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment1.22 (-42.9 to 59.1)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.9833 (p-value for testing mean = 0) · Mean difference (net): 0.15 · 95% CI -14.71 to 15.01
SecondaryChange in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Time frame:
12 weeks
Reported as:
Median · µg/L
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12
µg/LNTZ 500 mg BID
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 1210.50 (-133.2 to 177.5)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3957 (p-value for testing mean = 0) · Mean difference (net): 12.68 · 95% CI -17.79 to 43.16
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 123.53 (-21.1 to 38.0)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3440 (p-value for testing mean = 0) · Mean difference (net): 3.81 · 95% CI -4.39 to 12.01
SecondaryChange 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
Reported as:
Median · µg/L
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment
µg/LNTZ 500 mg BID
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment13.40 (-36.6 to 67.4)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0607 (p-value for testing mean = 0) · Mean difference (net): 15.22 · 95% CI -0.77 to 31.21
SecondaryPercent 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
Reported as:
Median · percentage of change
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment3.78 (-16.6 to 27.6)
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0644 (p-value for testing mean = 0) · Mean difference (net): 5.83 · 95% CI -0.39 to 12.05
SecondaryChange 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
Reported as:
Mean · score
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12
scoreNTZ 500 mg BID
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12-0.3665 ± 0.77812
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.0487 (p-value for testing mean = 0) · Mean difference (net): -0.3665 · 95% CI -0.7306 to -0.0023
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 1216.64 ± 136.529
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.5919 (p-value for testing mean = 0) · Mean difference (net): 16.64 · 95% CI -47.25 to 80.54
SecondaryChange 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
Reported as:
Mean · score
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment
scoreNTZ 500 mg BID
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment-0.2679 ± 0.43795
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1272 (p-value for testing mean = 0) · Mean difference (net): -0.2679 · 95% CI -0.6340 to 0.0983
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment15.02 ± 74.847
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.5881 (p-value for testing mean = 0) · Mean difference (net): 15.02 · 95% CI -47.55 to 77.59
SecondaryChange 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
Reported as:
Mean · score
Change in Fibrosis-4 Score From Baseline to Week 12
scoreNTZ 500 mg BID
Change in Fibrosis-4 Score From Baseline to Week 12-0.18 ± 0.516
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1458 · Mean difference (net): -0.18 · 95% CI -0.42 to 0.07
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Fibrosis-4 Score From Baseline to Week 12
percentage of changeNTZ 500 mg BID
Percent Change in Fibrosis-4 Score From Baseline to Week 12-11.53 ± 34.342
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.1495 (p-value for testing mean = 0) · Mean difference (net): -11.53 · 95% CI -27.61 to 4.54
SecondaryChange 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
Reported as:
Mean · score
Change in Fibrosis-4 Score From Baseline to End of Treatment
scoreNTZ 500 mg BID
Change in Fibrosis-4 Score From Baseline to End of Treatment-0.12 ± 0.328
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.3174 (p-value for testing mean = 0) · Mean difference (net): -0.12 · 95% CI -0.40 to 0.15
SecondaryPercent 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
Reported as:
Mean · percentage of change
Percent Change in Fibrosis-4 Score From Baseline to End of Treatment
percentage of changeNTZ 500 mg BID
Percent Change in Fibrosis-4 Score From Baseline to End of Treatment-8.02 ± 17.754
Statistical analysis
  • NTZ 500 mg BID · t-test, 2 sided · p = 0.2420 (p-value for testing mean = 0) · Mean difference (net): -8.02 · 95% CI -22.86 to 6.82

Adverse events

Collected over from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
NTZ 500 mg BID0/21 (0%)4/21 (19%)20/21 (95.2%)
Most frequent serious events
Most frequent serious events
EventNTZ 500 mg BID
NephrolithiasisRenal and urinary disorders1/21
MenometrorrhagiaReproductive system and breast disorders1/21
Lumbar Spinal StenosisMusculoskeletal and connective tissue disorders1/21
Atrial FibrillationCardiac disorders1/21
Angina UnstableCardiac disorders1/21
Coronary Artery DiseaseCardiac disorders1/21
cardiac failureCardiac disorders1/21
Most frequent other events
Showing 10 of 63
Most frequent other events
EventNTZ 500 mg BID
ChromaturiaRenal and urinary disorders7/21
DiarrhoeaGastrointestinal disorders5/21
Urinary tract infectionInfections and infestations5/21
Abdominal painGastrointestinal disorders3/21
NauseaGastrointestinal disorders3/21
fallInjury, poisoning and procedural complications3/21
Abdominal pain upperGastrointestinal disorders2/21
ConstipationGastrointestinal disorders2/21
Gastric ulcerGastrointestinal disorders2/21
Gastroenteritis viralInfections and infestations2/21

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)NTZ 500 mg BID
<=18 years0
Between 18 and 65 years17
>=65 years4
Age, Continuous
Age, Continuous(years)NTZ 500 mg BID
Mean55.2 ± 11.80
Sex: Female, Male
Sex: Female, Male(Participants)NTZ 500 mg BID
Female16
Male5
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)NTZ 500 mg BID
Hispanic or Latino13
Not Hispanic or Latino8
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)NTZ 500 mg BID
American Indian or Alaska Native1
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White19
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)NTZ 500 mg BID
United States21
Height at Screening
Height at Screening(cm)NTZ 500 mg BID
Mean164.4 ± 9.17
Baseline weight
Baseline weight(kg)NTZ 500 mg BID
Mean94.14 ± 17.793

1 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Pinnacle Clinical Research
    San Antonio, Texas 78229, United States
09

References and documents

Study documents

  • Study protocol · Aug 27, 2018
  • Study protocol · Oct 21, 2018
  • Study protocol · Mar 2, 2019
  • Study protocol · Aug 24, 2019
  • Study protocol · Feb 26, 2020
  • Study protocol · Apr 15, 2020
  • Statistical analysis plan · Apr 30, 2019
  • Statistical analysis plan · Apr 9, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 30, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03656068
Lead sponsor
Pinnacle Clinical Research, PLLC
Responsible party
Stephen A. Harrison (Principal Investigator, Pinnacle Clinical Research, PLLC) — Principal investigator
First posted
Sep 4, 2018
Start date
Dec 4, 2018
Primary completion
Nov 25, 2020
Completion
Nov 25, 2020
Results posted
Jun 30, 2022
Last update
Jun 30, 2022

Study contacts

Stephen Harrison, MD
principal investigator · Pinnacle Clinical Research

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.

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