Clinical trial NCT00446134: Taribavirin Phase 2 Dose Finding Study for the Treatment of Hepatitis C Virus (HCV)
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Keywords: Phase 2b Dose-Ranging Study
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2007-03-12
Enrollment: 278
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to select an optimal dose of taribavirin by comparing the efficacy and safety of 3 taribavirin dose levels, 20, 25, and 30 mg/kg/day, versus ribavirin 800 to 1400 mg/day based on body weight, both administered in combination with peginterferon alfa-2b to therapy-naive patients with chronic Hepatitis C Virus (HCV) genotype 1 infection.

Detailed description: The objective of the study is to select an optimal dose of taribavirin by comparing the efficacy and safety of 3 taribavirin dose levels, 20, 25, and 30 mg/kg/day, versus ribavirin 800 mg/day to 1400 mg/day based on subject body weight, with both drugs administered in combination with peginterferon alfa-2b to therapy-naive patients with chronic Hepatitis C Virus genotype 1 infection.

Eligibility criteria: Subject Inclusion Criteria

To be eligible for enrollment, patients must meet all of the following criteria:

1. At least 18 years of age
2. 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:

1. Positive HIV or HbsAg serology
2. 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)
3. 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
4. History of thalassemia or other hemoglobinopathies (even if the hemoglobin is normal)
5. Chronic hepatic disease other than hepatitis C
6. Organ or bone marrow transplant
7. 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
8. Female patients who are breast-feeding or have a positive pregnancy test at any time during the study
9. Males whose female partners are pregnant
10. 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
11. Patients who have participated in a clinical trial and have received an investigational drug within 30 days prior to screening
12. History of alcoholism or drug addiction 1 year prior to screening
13. 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
14. Chronic (\>4 weeks duration) diarrhea, including irritable bowel disease
15. Fibrosis score F4 (cirrhosis) based on Metavir or equivalent index
16. Weight \>128 kg or \<40 kg
17. Patients infected with mixed HCV genotypes

Primary outcomes:
measure: 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.
timeFrame: Treatment Week 12
Secondary outcomes:
measure: Patients With Anemia (Hemoglobin <10 g/dL) Up to Follow-up Week 24
timeFrame: Treatment Week Follow-Up 24
measure: Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24
timeFrame: Treatment Week Follow-Up 24
measure: Relapsers at Follow-Up Visit 24
timeFrame: Follow-Up Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, 8635 W. 3rd Street, Suite 590W
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Fred Poordad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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
citation: 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.