A Randomized Study to Evaluate the Safety, Tolerability and Antiviral Activity of ABT-450, ABT-333 and ABT-072 (Champion2)

AbbVie

Status and phase: Completed; Phase 2

Conditions: Hepatitis C Genotype 1; Hepatitis C; HCV; Chronic Hepatitis C Infection

Treatments: Drug: ABT-450; Drug: Ribavirin; Drug: ABT-333; Drug: ABT-072; Other: Placebo; Drug: Ritonavir; Drug: Peginterferon alpha-2a

Study type: Interventional

Funder types: Industry

Identifiers

NCT01074008

M11-602

Details and patient eligibility

About

This study assessed the safety, tolerability, pharmacokinetics, and antiviral activity of multiple oral doses of ABT-450/ritonavir (r), ABT-333 (also known as dasabuvir), or ABT-072 in hepatitis C virus (HCV), genotype 1-infected, treatment-naïve adults.

Full description

This was a Phase 2a, randomized, blinded, placebo-controlled, dose-ranging study in chronically, hepatitis C virus (HCV) genotype 1-infected participants designed to explore the safety, tolerability, pharmacokinetics, antiviral activity, as well as the evolution and persistence to resistance of ABT-450/r, ABT-333, or ABT-072. Participants were treated with ABT-450/r, ABT-333, or ABT-072 monotherapy for 3 days, followed by 81 days (12 weeks minus 3 days of monotherapy) of ABT-450/r, ABT-333, or ABT-072 combined with pegylated interferon/ribavirin (pegIFN/RBV), followed by 36 weeks of pegIFN/RBV alone. Participants randomized to an ABT-450/r treatment group who achieved rapid virologic response (RVR) and had HCV ribonucleic acid (RNA) levels < 25 IU/mL at all subsequent visits were eligible to stop pegIFN/RBV therapy on or after Week 24.

Enrollment: 74 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Chronic hepatitis C virus (HCV), genotype 1 infection (HCV ribonucleic acid level greater than or equal to 100,000 IU/mL) at screening
• Liver biopsy within 3 years with histology consistent with HCV-induced liver damage, with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV
• Treatment naïve male or female between the ages of 18 and 65
• Females must be post-menopausal for more than 2 years or surgically sterile
• Negative screen for drugs and alcohol
• Negative hepatitis B surface antigen (HBsAg) and anti-human immunodeficiency virus antibodies (anti-HIV Ab)
• No use of cytochrome P450 3A (CYP3A) and cytochrome P450 2C8 (CYP2C8) enzyme inducers or inhibitors within 1 month of dosing
• Be in a condition of general good health, as perceived by the investigator, other than HCV infection

Exclusion criteria

• Significant sensitivity to any drug
• Use of herbal supplements within 2 weeks prior to study drug dosing
• History of major depression within 2 years
• Prior treatment with any investigational or commercially available anti-HCV agents
• Abnormal laboratory tests

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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74 participants in 9 patient groups, including a placebo group

ABT-450/r (50/100 mg) once daily (QD) + pegIFN/RBV

Experimental group

Description:

Participants received 50 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: Ritonavir

Drug: ABT-450

Drug: Ribavirin

Drug: Peginterferon alpha-2a

ABT-450/r (100/100 mg) once daily (QD) + pegIFN/RBV

Experimental group

Description:

Participants received 100 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: Ritonavir

Drug: ABT-450

Drug: Ribavirin

Drug: Peginterferon alpha-2a

ABT-450/r (200/100 mg) once daily (QD) + pegIFN/RBV

Experimental group

Description:

Participants received 200 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: Ritonavir

Drug: ABT-450

Drug: Ribavirin

Drug: Peginterferon alpha-2a

ABT-072 (100 mg) once daily (QD) + pegIFN/RBV

Experimental group

Description:

Participants received 100 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: ABT-072

Drug: Ribavirin

Drug: Peginterferon alpha-2a

ABT-072 (300 mg) once daily (QD) + pegIFN/RBV

Experimental group

Description:

Participants received 300 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: ABT-072

Drug: Ribavirin

Drug: Peginterferon alpha-2a

ABT-072 (600 mg) once daily (QD) + pegIFN/RBV

Experimental group

Description:

Participants received 600 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: ABT-072

Drug: Ribavirin

Drug: Peginterferon alpha-2a

ABT-333 (400 mg) twice a day (BID) + pegIFN/RBV

Experimental group

Description:

Participants received 400 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: ABT-333

Drug: Ribavirin

Drug: Peginterferon alpha-2a

ABT-333 (800 mg) twice daily (BID) + pegIFN/RBV

Experimental group

Description:

Participants received 800 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Drug: ABT-333

Drug: Ribavirin

Drug: Peginterferon alpha-2a

Placebo + pegIFN/RBV

Placebo Comparator group

Description:

Participants received matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Treatment:

Other: Placebo

Drug: Ribavirin

Drug: Peginterferon alpha-2a