- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00446134
Taribavirin Phase 2 Dose Finding Study for the Treatment of Hepatitis C Virus (HCV)
Phase 2 Comparison of Weight-based Doses of Taribavirin Combined With Peginterferon Alfa-2b Versus Ribavirin Combined With Peginterferon Alfa-2b in Therapy-naïve Patients With Chronic Hepatitis C Virus Genotype 1 Infection
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90048
- Cedars-Sinai Medical Center, 8635 W. 3rd Street, Suite 590W
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Subject Inclusion Criteria
To be eligible for enrollment, patients must meet all of the following criteria:
- At least 18 years of age
- Diagnosed with compensated chronic HCV genotype 1 infection that has not been treated with interferon, peginterferon, ribavirin or any experimental therapy for >28 days
2a Serum HCV RNA >2000 copies/mL (780 IU/mL) 2b Liver biopsy performed within 3 years prior to screening consistent with chronic HCV infection 2c Criteria for compensated HCV infection, including normal prothrombin time, serum albumin and bilirubin levels (unless due to non-hepatitis factors) and no history or evidence of bleeding esophageal varices, ascites, or hepatic encephalopathy
3 History of alanine aminotransferase (ALT) elevation either within 6 months prior to screening, at screening, or on retest 2 weeks after a negative screening test, or histologic evidence of HCV infection and a detectable viral load
4 Platelet count ≥90,000/mm3
5 Absolute neutrophil count ≥1200/mm3
6 Hemoglobin ≥12.0 g/dL for females or ≥13.0 g/dL for males
7 Antinuclear antibody (ANA) titer ≤1:320
8 Serum creatinine <1.5 mg/dL
9 HbA1c ≤8.5% for diabetic patients
10 Normal or adequately controlled TSH on prescription medication
11 Alpha fetoprotein (AFP) <20 ng/mL or hepatocellular carcinoma ruled out (ultrasound, CT or MRI scan) within 6 months prior to the study (Patients with an AFP >20 ng/mL must have ongoing hepatocellular carcinoma screening during study as part of the patient's routine medical care)
12 All other clinical laboratory values within normal limits, unless judged not clinically significant by the investigator
13 Sterile or infertile (defined as vasectomy, tubal ligation, postmenopausal, or hysterectomy), or willing to use an approved method of double-barrier contraception (hormonal plus barrier or barrier plus barrier, eg, diaphragm plus condom) from the time of first dose administration until 6 months after the last dose
14 Capable of understanding instructions, adhering to study schedules and requirements, and willing to provided informed consent
Subject Exclusion Criteria
Patients who have any of the following during the screening or Day 1 visit are not eligible for enrollment in this study:
- Positive HIV or HbsAg serology
- Severe psychiatric or neuropsychiatric disorders including severe depression, history of suicidal ideations or suicide attempt(s). (This would include patients with a history of suicidal ideations or suicide attempt(s) that occurred when the patient was a minor or many years ago; if the event occurred while under the influence of alcohol or drugs; if the suicidal ideations or suicide attempt(s) were connected to a traumatic event; if the patient was not hospitalized or treated; if the patient has obtained psychiatric clearance for treatment)
- History or clinical manifestations of significant metabolic, hematological, pulmonary, ischemic or unstable heart disease, gastrointestinal, neurological, renal, urological, endocrine, ophthalmologic (including severe retinopathy), or immune mediated disease
- History of thalassemia or other hemoglobinopathies (even if the hemoglobin is normal)
- Chronic hepatic disease other than hepatitis C
- Organ or bone marrow transplant
- Chronic (greater than 30 days) use of immunosuppressive medications including steroids in doses equivalent to 10 mg of prednisone or higher, 30 days prior to and anytime during the course of the study
- Female patients who are breast-feeding or have a positive pregnancy test at any time during the study
- Males whose female partners are pregnant
- Patients who have had a malignancy diagnosed and/or treated within the past 5 years, except for localized squamous or basal cell cancers treated by local excision
- Patients who have participated in a clinical trial and have received an investigational drug within 30 days prior to screening
- History of alcoholism or drug addiction 1 year prior to screening
- The use of methadone, buprenorphine or any similar drug, regardless of the prescribed indication or the length of time the patient has been on the drug
- Chronic (>4 weeks duration) diarrhea, including irritable bowel disease
- Fibrosis score F4 (cirrhosis) based on Metavir or equivalent index
- Weight >128 kg or <40 kg
- Patients infected with mixed HCV genotypes
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1: Drug
Oral taribavirin tablet 20 mg/kg/day (Actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
|
Oral (200 mg) Tablet: 20mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
Oral (200 mg) Tablet: 25mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
Oral (200mg)Tablet: 30mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
|
Experimental: Group 2: Drug
Oral taribavirin tablet 25 mg/kg/day (Actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
|
Oral (200 mg) Tablet: 20mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
Oral (200 mg) Tablet: 25mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
Oral (200mg)Tablet: 30mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
|
Experimental: Group 3: Drug
Oral taribavirin 30 mg/kg/day (Actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
|
Oral (200 mg) Tablet: 20mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
Oral (200 mg) Tablet: 25mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
Oral (200mg)Tablet: 30mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
|
Active Comparator: Group 4: Drug
Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
|
Oral (200mg)Tablet: 800 mg/day, 1000 mg/day, 1200 mg/day, or 1400 mg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection.
Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12.
Time Frame: Treatment Week 12
|
The primary efficacy endpoint was the numbers of responders at Treatment Week (TW) 12. Responders are defined as patients achieving either viral negativity or a partial response (PR).
Viral negativity is defined as <100 copies/mL serum HCV RNA.
A PR is defined as < 100 copies/mL serum HCV RNA and at least a 2-log decrease from baseline in serum HCV RNA levels.
Responder rates with corresponding 95% confidence intervals were estimated for each treatment group.
|
Treatment Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patients With Anemia (Hemoglobin <10 g/dL) Up to Follow-up Week 24
Time Frame: Treatment Week Follow-Up 24
|
The primary safety endpoint will be the numbers of patients with hemoglobin <10 g/dL (anemia) at any time during the treatment period.
The comparison of anemia rates between taribavirin and ribavirin groups will be carried out using the Fisher's exact test or Chi-square test.
The 95% confidence interval of the difference in proportion will be analyzed.
|
Treatment Week Follow-Up 24
|
Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24
Time Frame: Treatment Week Follow-Up 24
|
Treatment Week Follow-Up 24
|
|
Relapsers at Follow-Up Visit 24
Time Frame: Follow-Up Week 24
|
Includes patients who had undetectable Hepatitis Virus C (HVC) Ribonucleic Acid (RNA) at their last visit on drug.
|
Follow-Up Week 24
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Fred Poordad, MD, Cedars-Sinai Medical Center
Publications and helpful links
General Publications
- Poordad F, Lawitz E, Pozza R, et al. Efficacy and safety of weight-based regimens of taribavirin or ribavirin, given with peginterferon alfa-2b, 12 weeks after treatment (SVR12) in naive patients with genotype 1 hepatitis C. J Hepatol. 2009;50 Suppl 1:S8
- Poordad F, Lawitz E, Chun E, Hammond J. Treatment week 12 results of weight-based taribavirin versus weight-based ribavirin, both with peginterferon alfa-2b, in naive chronic hepatitis C, genotype 1 patients. J Hepatol. 2008;48 Suppl 2:S373
- Poordad F, Lawitz E, Shiffman ML, Hassanein T, Muir AJ, Bacon BR, Heise J, Halliman D, Chun E, Hammond J. Virologic response rates of weight-based taribavirin versus ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C. Hepatology. 2010 Oct;52(4):1208-15. doi: 10.1002/hep.23827.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- Hepatitis A
- Hepatitis C
- Hepatitis, Chronic
- Hepatitis C, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Ribavirin
- Taribavirin
Other Study ID Numbers
- RNA003142-204
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Hepatitis C
-
Hospices Civils de LyonCompleted
-
Sohag UniversityRecruiting
-
Beni-Suef UniversityCompletedChronic Hepatitis C Virus InfectionEgypt
-
Humanity and Health Research CentreBeijing 302 HospitalCompletedChronic Hepatitis C InfectionChina
-
Hadassah Medical OrganizationXTL BiopharmaceuticalsWithdrawnChronic Hepatitis C Virus InfectionIsrael
-
Hadassah Medical OrganizationUnknownChronic Hepatitis C Virus InfectionIsrael
-
AbbVie (prior sponsor, Abbott)CompletedHepatitis C | Chronic Hepatitis C Infection | HCV | Hepatitis C Genotype 1United States, Puerto Rico
-
Beni-Suef UniversityCompletedChronic Hepatitis C Virus Infection
-
Humanity and Health Research CentreBeijing 302 HospitalCompletedChronic Hepatitis C InfectionChina
Clinical Trials on Taribavirin
-
Bausch Health Americas, Inc.TerminatedHepatitis C, ChronicUnited States
-
Bausch Health Americas, Inc.Completed
-
Bausch Health Americas, Inc.CompletedChronic Hepatitis CUnited States, Spain, Italy, Australia, Canada, Poland, Puerto Rico, Russian Federation, Argentina, France, Israel, United Kingdom