A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)

AbbVie

Status and phase: Completed; Phase 2

Conditions: Hepatitis C, Chronic

Treatments: Drug: ABT-267; Drug: ABT-450/r; Drug: Ribavirin (RBV)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01685203

2011-005762-38 (EudraCT Number)

M13-393

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.

Full description

This was a Phase 2, randomized, open-label, combination treatment study of the 2-DAA regimen (ABT-450 150 mg QD + ritonavir 100 mg QD + ABT-267 25 mg QD) in adult HCV GT1b-infected treatment-naïve and Pegylated-interferon/ribavirin (pegIFN/RBV) treatment-experienced participants without cirrhosis and with compensated cirrhosis, and in adult GT4-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis. Treatment Group 5 was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher sustained virologic response (SVR) rates among participants receiving the 2-DAA regimen with RBV. All other groups completed the study.

Enrollment: 316 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile

• Subjects must meet one of the following:

  • Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR
  • Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV);

• Body mass index (BMI) is ≥ 18 to < 38 kg/m^2.

• Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening.

• Subject has plasma HCV RNA level > 10,000 IU/mL at Screening

Exclusion criteria

• History of severe, life-threatening or other significant sensitivity to any drug.
• Females who were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV.
• Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
• Positive test result for hepatitis B surface antigen or anti-Human Immunodeficiency Virus (HIV) antibodies.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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316 participants in 8 patient groups

Group 1

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants

Treatment:

Drug: ABT-450/r

Drug: ABT-267

Group 2

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants

Treatment:

Drug: ABT-450/r

Drug: ABT-267

Group 3

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants

Treatment:

Drug: ABT-450/r

Drug: ABT-267

Group 4

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if \< 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants

Treatment:

Drug: Ribavirin (RBV)

Drug: ABT-450/r

Drug: ABT-267

Group 5

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants

Treatment:

Drug: ABT-450/r

Drug: ABT-267

Group 6

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if \< 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants

Treatment:

Drug: Ribavirin (RBV)

Drug: ABT-450/r

Drug: ABT-267

Group 7

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis

Treatment:

Drug: ABT-450/r

Drug: ABT-267

Group 8

Experimental group

Description:

ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis

Treatment:

Drug: ABT-450/r

Drug: ABT-267