Study of Nitazoxanide, Peginterferon Alfa-2a and Ribavirin for the Treatment of Hepatitis C

Chronic Hepatitis C Clinical Trial

— STEALTHC-2  

Official title:

Phase II, Randomized, Double-blind, Placebo-controlled Study of Nitazoxanide in Combination With Peginterferon Alfa-2a and Ribavirin in Patients With Hepatitis C Who Have Failed to Respond to a Prior Course of Peginterferon and Ribavirin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00495391
• Other study ID #: RM01-2025
• Status: Completed
• Phase: Phase 2
• First received: July 2, 2007
• Last updated: April 8, 2014
• Start date: July 2007
• Est. completion date: February 2010

Study information

• Verified date: April 2014
• Source: Romark Laboratories L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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 patients that have previously failed to respond to treatment with peginterferon and ribavirin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic hepatitis C genotype 1.

• Failed to respond to =12 weeks of peginterferon and ribavirin (<2 log10 drop in Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 12 or detectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 24).

Exclusion Criteria:

• 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 antigen 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) >28.

• 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Nitazoxanide
One oral 500 mg nitazoxanide tablet twice daily for 52 weeks.
• Placebo
One oral placebo tablet twice daily for 52 weeks.

Biological:
• Peginterferon alfa-2a
Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.

Drug:
• Ribavirin
1000 mg (if <75 kg body weight) or 1200 mg (if =75 kg body weight) ribavirin in divided daily doses for 48 weeks.

Locations

Country	Name	City	State
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Florida Hepatology	Gainesville	Florida
United States	Florida Center for Gastroenterology	Largo	Florida
United States	Nashville Medical Research Institute	Nashville	Tennessee
United States	Yale University Digestive Diseases	New Haven	Connecticut
United States	Weill Cornell Medical College	New York	New York
United States	VA Palo Alto Healthcare System	Palo Alto	California
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Romark Laboratories L.C.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No