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

• End of treatment response (HCV RNA below lower limit of detection) [ Time Frame: At end of treatment ] [ Designated as safety issue: No ]
• Early virologic response (HCV RNA below lower limit of detection) [ Time Frame: After 12 weeks combination treatment ] [ Designated as safety issue: No ]
• Rapid virologic response (HCV RNA below lower limit of detection) [ Time Frame: After 4 weeks combination treatment ] [ Designated as safety issue: No ]
• Changes in ALT [ Time Frame: From baseline to weeks 8, 16, end of treatment and end of follow-up ] [ Designated as safety issue: No ]

• End of treatment response (HCV RNA below lower limit of detection) [ Time Frame: At end of treatment ]
• Early virologic response (HCV RNA below lower limit of detection) [ Time Frame: After 12 weeks combination treatment ]
• Rapid virologic response (HCV RNA below lower limit of detection) [ Time Frame: After 4 weeks combination treatment ]
• Changes in ALT [ Time Frame: From baseline to weeks 8, 16, end of treatment and end of follow-up ]

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.

• Drug: Nitazoxanide
  One oral 500 mg nitazoxanide tablet twice daily for 52 weeks.
  Other Name: Alinia
• Drug: Placebo
  One oral placebo tablet twice daily for 52 weeks.
• Biological: Peginterferon alfa-2a
  Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.
  Other Name: PEGASYS
• 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.
  Other Name: COPEGUS

• Active Comparator: 1
  Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks.
  Interventions:

  • Drug: Nitazoxanide
  • Biological: Peginterferon alfa-2a
  • Drug: Ribavirin
• Placebo Comparator: 2
  Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks.
  Interventions:

  • Drug: Placebo
  • Biological: Peginterferon alfa-2a
  • Drug: Ribavirin

Inclusion Criteria:

• Chronic hepatitis C genotype 1.
• Failed to respond to ≥12 weeks of peginterferon and ribavirin (<2 log10 drop in HCV RNA at week 12 or detectable 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-HAV IgM Ab, HBsAg, anti-HBc IgM Ab or anti-HIV Ab.
• Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, CTP score >6 or 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 ULN.
• Hypothyroidism or hyperthyroidism not effectively treated with medication.
• HgbA1c >7.5 or history of diabetes mellitus.
• 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.