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

AbbVie

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C Virus Infection

Treatments: Drug: ABT-333; Drug: Ribavirin; Drug: Pegylated interferon; Other: Placebo for ABT-333

Study type: Interventional

Funder types: Industry

Identifiers

NCT00851890

M10-380

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

30 participants in 4 patient groups, including a placebo group

ABT-333 (300 mg) twice daily (BID) + pegIFN/RBV

Experimental group

Description:

Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: Ribavirin

Drug: ABT-333

Drug: Pegylated interferon

ABT-333 (600 mg) twice daily (BID) + pegIFN/RBV

Experimental group

Description:

Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: Ribavirin

Drug: ABT-333

Drug: Pegylated interferon

ABT-333 (1200 mg) once daily (QD) + pegIFN/RBV

Experimental group

Description:

Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: Ribavirin

Drug: ABT-333

Drug: Pegylated interferon

Placebo + pegIFN/RBV

Placebo Comparator group

Description:

Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: Ribavirin

Drug: Pegylated interferon

Other: Placebo for ABT-333