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

NCT00495391 | Completed Phase 2 Results DMC

• 1 other identifier: RM01-2025
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Chronic Hepatitis C

Keywords

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• End of Treatment Response (HCV RNA Below Lower Limit of Detection)

  At end of treatment

• Early Virologic Response (HCV RNA Below Lower Limit of Detection)

  After 12 weeks combination treatment

• Rapid Virologic Response (HCV RNA Below Lower Limit of Detection)

  After 4 weeks combination treatment

• Changes in ALT

  From baseline to week 8

• Changes in ALT

  From baseline to week 16

Study Arms (2)

1

ACTIVE COMPARATOR

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.

Drug: Nitazoxanide; Biological: Peginterferon alfa-2a; Drug: Ribavirin

2

PLACEBO COMPARATOR

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.

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

Interventions

Nitazoxanide DRUG

One oral 500 mg nitazoxanide tablet twice daily for 52 weeks.

Also known as: Alinia

1

Placebo DRUG

One oral placebo tablet twice daily for 52 weeks.

2

Peginterferon alfa-2a BIOLOGICAL

Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.

Also known as: PEGASYS

1; 2

Ribavirin DRUG

1000 mg (if \<75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks.

Also known as: COPEGUS

1; 2

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Romark Laboratories L.C.: lead

Study Sites (10)

VA Palo Alto Healthcare System

Palo Alto, California, 94304, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Yale University Digestive Diseases

New Haven, Connecticut, 06520, United States

Location

University of Florida Hepatology

Gainesville, Florida, 32610, United States

Location

Florida Center for Gastroenterology

Largo, Florida, 33777, United States

Location

Atlanta Gastroenterology Associates

Atlanta, Georgia, 30308, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Nashville Medical Research Institute

Nashville, Tennessee, 37205, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

nitazoxanide; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Marc Ayers
• Organization: Romark Laboratories, L.C.

Marc.Ayers@romark.com

813-282-8544

Study Officials

• David Nelson, MD

  University of Florida Hepatology

  PRINCIPAL INVESTIGATOR

• Stephen Harrison, MD

  Brooke Army Medical Center

  PRINCIPAL INVESTIGATOR

• Arthur Berman, DO

  Florida Center for Gastroenterology

  PRINCIPAL INVESTIGATOR

• Ronald Pruitt, MD

  Nashville Medical Research Institute

  PRINCIPAL INVESTIGATOR

• Ahmed Aijaz, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Ramsey Cheung, MD

  VA Palo Alto Health Care System

  PRINCIPAL INVESTIGATOR

• Ira Jacobson, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• Mitchell Shiffman, MD

  McGuire VA Medical Center

  PRINCIPAL INVESTIGATOR

• Joseph Lim, MD

  Yale University Digestive Diseases

  PRINCIPAL INVESTIGATOR

• Norman Gitlin, MD

  Atlanta Gastroenterology Associates

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2007
• First Posted: July 3, 2007
• Study Start: July 1, 2007
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: May 8, 2014
• Results First Posted: January 6, 2014

Record last verified: 2014-04

Locations

US (10)