Taribavirin Phase 2 Dose Finding Study for the Treatment of Hepatitis C Virus (HCV)

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00446134
• Other study ID #: RNA003142-204
• Status: Completed
• Phase: Phase 2
• First received: March 8, 2007
• Last updated: June 20, 2012
• Start date: March 2007
• Est. completion date: April 2009

Study information

• Verified date: June 2012
• Source: Valeant Pharmaceuticals International, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 278
• Est. completion date: April 2009
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Taribavirin
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.
• Taribavirin
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.
• Taribavirin
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.
• Ribavirin
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.

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center, 8635 W. 3rd Street, Suite 590W	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Valeant Pharmaceuticals International, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (4)

Lawitz E, Muir A, Poordad F, et al. Treatment week 24 results of weight-based taribavirin versus weight-based ribavirin, both with peginterfon alfa-2b, in naive chronic hepatitis C, genotype 1 patients. Hepatology. 2008;48 Suppl 1:433A

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, Hassanein T, et al. Sustained virologic response results for weight-based taribavirin versus weight-based ribavirin, in naive chronic hepatitis C, genotype 1 patients. Hepatology. 2009;50 Suppl 1:334A

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	No
Secondary	Patients With Anemia (Hemoglobin <10 g/dL) Up to Follow-up Week 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	Yes
Secondary	Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24		Treatment Week Follow-Up 24	No
Secondary	Relapsers at Follow-Up Visit 24	Includes patients who had undetectable Hepatitis Virus C (HVC) Ribonucleic Acid (RNA) at their last visit on drug.	Follow-Up Week 24	No