An Evaluation of the Safety and Efficacy of Nitazoxanide on Collagen Turnover in NASH Patients With Fibrosis
Condition: Non-alcoholic Steatohepatitis; Fatty Liver; Fibrosis, Liver; Compensated Cirrhosis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Fibrosis
Intervention: Nitazoxanide 500mg BID
Intervention description: Patients will receive 500mg of Nitazoxanide BID daily for 24 weeks
Intervention MeSH terms: Nitazoxanide
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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).