A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Condition(s) targeted: Chronic Hepatitis C Virus Infection

Intervention: ABT-333 (Drug); Placebo for ABT-333 (Other); Pegylated interferon (Drug); Ribavirin (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: AbbVie (prior sponsor, Abbott)

Official(s) and/or principal investigator(s):
Daniel Cohen, MD, Study Director, Affiliation: AbbVie

The purpose of this study was to assess the safety, tolerability, pharmacokinetics and antiviral activity of ABT-333 (also known as dasabuvir) in treatment-naïve, hepatitis C virus (HCV)-infected participants.

Official title: A Blinded, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment

Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28

Maximum Plasma Concentration (Cmax) of ABT-333

Time to Maximum Plasma Concentration (Tmax) of ABT-333

Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC12) of ABT-333

Serum Concentrations of Pegylated Interferon (pegIFN)

Plasma Concentrations of Ribavirin (RBV)

Number of Participants Having Treatment-emergent Adverse Events (AEs)

Secondary outcome:

Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit

Percentage of Participants With at Least a 2 log10 Maximal Decrease in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Treatment

Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 25 IU/mL (the Lower Limit of Quantitation [LLOQ]) at Day 28 or Final Visit

Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 10 IU/mL (Lower Limit of Detection [LLOD]) at Day 28 or Final Visit

Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28

Number of Participants With Maximal Phenotypic Resistance to ABT-333 >10 Fold Relative to Baseline Through Day 28

Detailed description: This was a Phase 2a, blinded, randomized, placebo-controlled clinical trial in hepatitis C virus (HCV)-infected adults with 2 planned sequential evaluations, Part 1 and Part 2. The study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-333 or placebo monotherapy, followed by 26 days of ABT-333 or placebo with pegylated interferon a-2a (pegIFN) and ribavirin (RBV) combination therapy. Review of safety and efficacy in Part 1 of the study showed similar response rates across ABT-333 doses so Part 2 of the study was not performed. The study also assessed emergence of resistant HCV in conjunction with kinetics of viral load decay and rebound in treatment-naïve, HCV-infected participants.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Participant has provided written consent.

- If female, participant is postmenopausal or surgically sterile.

- If male, must be practicing two effective methods of birth control.

- Participant is hepatitis C virus (HCV) genotype 1 with HCV ribonucleic acid levels

>50,000 IU/mL.

- Participants must demonstrate chronic hepatitis C infection for at least 6 months

prior to study enrollment.

- Participants must have a liver biopsy with histology consistent with HCV-induced

liver damage, and with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV.

- Condition of general good health other then HCV infection.

- Participants with a history of thyroid disease must have a thyroid stimulating

hormone (TSH) value in the normal range. Exclusion Criteria:

- No prior history of receiving therapy for HCV infection.

- Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B

surface antigen (HBsAg), or human immunodeficiency virus antibody (HIV Ab).

- Pregnant or breastfeeding females or male partners of women who are pregnant.

- History of seizures or cancer.

- History of major depressive disorder within 2 years.

- Any current or past history of cirrhosis.

- Any cause of liver disease other than chronic HCV infection.

Site Reference ID/Investigator# 16182, Santurce 00909, Puerto Rico

Site Reference ID/Investigator# 16103, Anaheim, California 92801, United States

Site Reference ID/Investigator# 16124, Los Angeles, California 90048, United States

Site Reference ID/Investigator# 16102, Orlando, Florida 32803, United States

Site Reference ID/Investigator# 16105, Baton Rouge, Louisiana 70808, United States

Site Reference ID/Investigator# 16106, Chapel Hill, North Carolina 27599-7584, United States

Site Reference ID/Investigator# 16107, Dallas, Texas 75203, United States

Site Reference ID/Investigator# 16123, San Antonio, Texas 78215, United States

Starting date: March 2009
Last updated: December 29, 2014