Study of Nitazoxanide, Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Hepatitis C Patients (STEALTHC-3)

Phase II, Randomized, Double-blind, Placebo-controlled Study of Nitazoxanide in Combination With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Patients With Hepatitis C

The purpose of this study is to determine if nitazoxanide in combination with peginterferon alfa-2a and ribavirin is safe and effective in treating chronic hepatitis C in treatment-naive patients.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Nitazoxanide; Biological: Peginterferon alfa-2a; Drug: Ribavirin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Palo Alto VA Healthcare System
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Bay Pines, Florida, United States, 33744
      • Bay Pines VA Healthcare System
    • Largo, Florida, United States, 33777
      • Florida Center for Gastroenterology
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Gastroenterology Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10021
      • New York Presbyterian-Weill Medical College of Cornell University
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Nashville Medical Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Metropolitan Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic hepatitis C genotype 1.

Exclusion Criteria:

• Patients that have previously received treatment with any interferon or interferon-based treatment for chronic hepatitis C.
• Females of child-bearing age who are either pregnant, breast-feeding or not using birth control and are sexually active.
• Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active.
• Other causes of liver disease including autoimmune hepatitis.
• Transplant recipients receiving immune suppression therapy.
• Screening tests positive for Anti-Hepatitis A Virus Immunoglobulin M Antibody (anti-HAV IgM Ab), Hepatitis B's antigen (HBsAg), Anti-Hepatitis B core Immunoglobulin M Antibody (anti-HBc IgM Ab) or Anti-Human Immunodeficiency Virus Antibody (anti-HIV Ab).
• Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, Child-Turcotte-Pugh (CTP) score >6 or Model for End-stage Liver Disease (MELD) score >8.
• Alcohol consumption of >40 grams per day or an alcohol use pattern that will interfere with the study.
• Absolute neutrophil count <1500 cells/mm3; platelet count <135,000 cells/mm3; hemoglobin <12 g/dL for women and <13 g/dL for men; or serum creatinine concentration ≥1.5 times Upper Limit of Normal (ULN).
• Hypothyroidism or hyperthyroidism not effectively treated with medication.
• Hemoglobin A1C (HgbA1c) >7.5 or history of diabetes mellitus.
• Body Mass Index (BMI) >34.
• History or other clinical evidence of significant or unstable cardiac disease.
• History or other clinical evidence of chronic pulmonary disease associated with functional impairment.
• Serious or severe bacterial infection(s).
• Ulcerative or hemorrhagic/ischemic colitis.
• Pancreatitis.
• History of severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization.
• History of uncontrolled severe seizure disorder.
• Requires concomitant theophylline or methadone.
• History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids.
• History or other evidence of severe retinopathy or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension.
• Hemoglobinopathies.
• History of hypersensitivity or intolerance to nitazoxanide or any of the excipients comprising the nitazoxanide tablets, peginterferon alfa-2a injectable solution or ribavirin tablets.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; One nitazoxanide 500 mg tablet orally with food twice daily (b.i.d.) for 4 weeks followed by 500 mg nitazoxanide b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks.	Drug: Nitazoxanide; One nitazoxanide 500 mg tablet orally with food twice daily (b.i.d.) for 4 weeks followed by 500 mg nitazoxanide b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks.; Other Names: Alinia; Biological: Peginterferon alfa-2a; One weekly injection of 180µg of peginterferon α-2a for 48 weeks.; Other Names: PEGASYS; Drug: Ribavirin; Weight-based ribavirin for 48 weeks.; Other Names: COPEGUS
Placebo Comparator: 2; One placebo tablet orally with food twice daily (b.i.d.) for 4 weeks followed by placebo b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks.	Biological: Peginterferon alfa-2a; One weekly injection of 180µg of peginterferon α-2a for 48 weeks.; Other Names: PEGASYS; Drug: Ribavirin; Weight-based ribavirin for 48 weeks.; Other Names: COPEGUS; Drug: Placebo; One placebo tablet orally with food twice daily (b.i.d.) for 4 weeks followed by placebo b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Virologic Response (HCV RNA Below Lower Limit of Detection)	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection 24 weeks after the end of treatment. All others were considered non-responders.	24 weeks after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
End of Treatment Response (HCV RNA Below Lower Limit of Detection)	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection at the end of treatment. All others were considered non-responders.	At end of treatment
Early Virologic Response (HCV RNA Below Lower Limit of Detection)	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 12 weeks of combination therapy.	After 12 weeks combination treatment
Rapid Virologic Response (HCV RNA Below Lower Limit of Detection)	Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 4 weeks of combination therapy.	After 4 weeks combination treatment
Changes in ALT	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.	From baseline to week 8
Changes in ALT	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.	From baseline to end of treatment
Changes in ALT	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up.	From baseline to end of follow up
Changes in ALT	This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up	From baseline to week 16

Collaborators and Investigators

• Sponsor: Romark Laboratories L.C.
• Investigators: Principal Investigator: Arthur Berman, DO, Florida Center for Gastroenterology; Principal Investigator: Norman Gitlin, MD, Atlanta Gastroenterology Associates; Principal Investigator: Raymond Chung, MD, Massachusetts General Hospital; Study Director: Emmet B Keeffe, MD, MACP, Romark Laboratories L.C.; Principal Investigator: Joseph K Lim, MD, Yale University; Principal Investigator: Ira Jacobson, MD, New York Presbyterial-Weill Medical College of Cornell University; Principal Investigator: Mitchell L Shiffman, MD, McGuire Veteran's Administration Medical Center; Principal Investigator: Ronald E Pruitt, MD, Nashville Medical Research Institute; Principal Investigator: Bruce Bacon, MD, St. Louis University Medical Center; Principal Investigator: David Johnson, MD, Bay Pines VA Healthcare System; Principal Investigator: Vinod Rustgi, MD, Metropolitan Research; Principal Investigator: Aijaz Ahmed, MD, Stanford University

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: March 11, 2008
• First Submitted That Met QC Criteria: March 11, 2008
• First Posted (Estimate): March 18, 2008

Study Record Updates

• Last Update Posted (Estimate): February 10, 2014
• Last Update Submitted That Met QC Criteria: January 9, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Hepatitis C, Chronic
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antiparasitic Agents; Ribavirin; Peginterferon alfa-2a; Nitazoxanide
• Other Study ID Numbers: RM01-2026