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

NCT03656068 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NTZ-218-1
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of Nitazoxanide (NTZ) 500mg Twice Daily (BID) after 24 weeks of treatment in patients with NASH induced Stage 2 or Stage 3 fibrosis

Conditions

Non-alcoholic Steatohepatitis; Fatty Liver; Fibrosis, Liver; Compensated Cirrhosis

Outcome Measures

Primary Outcomes (11)

• 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).

  28 weeks

• 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).

  28 weeks

• 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).

  28 weeks

• 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).

  28 weeks

• 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).

  28 weeks

• 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.

  28 weeks

• 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

  28 weeks

• 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.

  28 weeks

• 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

  28 weeks

• 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.

  28 weeks

• 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.

  28 weeks

Secondary Outcomes (72)

• Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment

  From baseline to end of treatment (Visit 10, Week 24 or early termination)

• Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment

  From baseline to end of treatment (Visit 10, Week 24 or early termination)

• Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment

  From baseline to end of treatment (Visit 10, Week 24 or early termination)

• Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment

  From baseline to end of treatment (Visit 10, Week 24 or early termination)

• Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®

  24 weeks

Study Arms (1)

Open label NTZ

EXPERIMENTAL

Open label. All patients will receive study drug

Drug: Nitazoxanide 500mg BID

Interventions

Nitazoxanide 500mg BID DRUG

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

Also known as: NTZ

Open label NTZ

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged from 18 to 75 years inclusive the Screening Visit.
• Must provide signed written informed consent and agree to comply with the study protocol.
• Females participating in this study must be of non-childbearing potential or using highly efficient contraception for the full duration of the study
• 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).
• 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).
• 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.

You may not qualify if:

• History of efficient bariatric surgery within 5 years prior to Screening, or planned bariatric surgery in the course of the study.
• 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).
• Weight loss of more than 10% within 6 months prior to Randomization.
• Patient with any history or presence of decompensated cirrhosis.
• 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.
• Current or history of other substance abuse within 1 year prior to screening.
• Pregnant or lactating females or females planning to become pregnant during the study period.
• Other well documented causes of chronic liver disease according to standard diagnostic procedures including, but not restricted to:
• Positive hepatitis B surface antigen (HBsAg)
• Positive Hepatitis C virus (HCV) RNA, (tested for in case of known cured HCV infection, or positive HCV Ab at Screening)
• Suspicion of drug-induced liver disease
• Alcoholic liver disease
• Autoimmune hepatitis
• Wilson's disease
• Primary biliary cirrhosis, primary sclerosing cholangitis

Sponsors & Collaborators

• Pinnacle Clinical Research, PLLC: lead

Study Sites (1)

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver; Liver Cirrhosis

Interventions

nitazoxanide; BID protein, human

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Stephen Harrison, MD
• Organization: Pinnacle Clinical Research

stephenharrison87@gmail.com

210-982-0320

Study Officials

• Stephen Harrison, MD

  Pinnacle Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: September 4, 2018
• Study Start: December 4, 2018
• Primary Completion: November 25, 2020
• Study Completion: November 25, 2020
• Last Updated: June 30, 2022
• Results First Posted: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)