A Study to Evaluate the Safety and Effect of Treatment With Experimental Antiviral Drugs in Combination With Peginterferon Alpha-2a and Ribavirin in People With Hepatitis C Virus Who Did Not Respond to Treatment in a Previous AbbVie/Abbott Combination Study

AbbVie

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C

Treatments: Drug: Ribavirin (RBV); Drug: pegylated interferon alpha-2a (pegIFN); Drug: ABT-450/r; Drug: ABT-267

Study type: Interventional

Funder types: Industry

Identifiers

NCT01609933

M13-101

Details and patient eligibility

About

A study to evaluate the safety and effect of treatment with experimental antiviral drugs in combination with peginterferon alpha-2a and ribavirin in people with hepatitis C virus who did not respond to treatment in a previous AbbVie/Abbott combination study.

Enrollment: 32 patients

Sex: All

Ages: 18 to 71 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Main Inclusion: To be enrolled in this protocol, subjects must meet all of the following inclusion criteria:

• Subject must have experienced virologic failure as defined in a previous AbbVie/Abbott direct-acting antiviral (DAA) combination trial.
• Female subjects of childbearing potential must be willing to use two effective forms of birth control (not including oral contraceptives or contraceptives containing ethinyl estradiol) while receiving study drug and for 7 months (or per local ribavirin label) after stopping study drug.
• Males must be surgically sterile or have male partners only or agree to practice two effective forms of birth control throughout the course of the study, starting with Study Day 1 and for 7 months (or per local ribavirin label) after the last dose of study drug, unless abstinent from sexual intercourse.
• Subject must be considered an appropriate candidate for peginterferon (pegIFN) alpha-2a, ribavirin (RBV), ABT-450/ritonavir (r) and ABT-267 therapy in the opinion of the investigator.
• Subject is infected with hepatitis C virus (HCV) genotype 1 at screening.

Subjects diagnosed with cirrhosis must also meet the following criteria:

• Compensated cirrhosis defined as Child-Pugh score of ≤ 6 at Screening.
• Absence of hepatocellular carcinoma based on a negative ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months prior to Screening or during the Screening period.

Exclusion criteria

• In subjects with a prior null or partial response to pegIFN/RBV treatment at any time prior to pre-screening for this study or any prior failure with pegIFN/RBV plus telaprevir, the presence of variants relative to the appropriate prototypic reference sequence (H77 for 1a or Con1 for 1b) at any of the following positions: NS3 155, 156, or 168; or NS5A 28, 29, 30, 31, 32, 58, or 93.
• Females who are pregnant or plan to become pregnant, or breast-feeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of RBV.
• Use of known strong inducers (e.g., phenobarbital, rifampin, carbamazepine, St. John's Wort) of Cytochrome P450 3A (CYP3A) within 2 weeks prior to study drug administration.
• Use of any medications contraindicated for use with pegIFN alpha-2a, RBV or ritonavir within 2 weeks prior to study drug administration. Prior to entering the study, subjects must be able to safely discontinue the contraindicated medication or switch to an acceptable alternative under supervision of the investigator.
• Discontinuation of antiviral therapy due to intolerance or a DAA- or RBV-associated adverse event in a previous AbbVie/Abbott DAA combination study.

Subjects with compensated cirrhosis must also not meet the following criteria:

• Any current or past clinical evidence of Child-Pugh B or C Classification or clinical history of liver decompensation such as ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy.
• Serum Alpha-Fetoprotein (sAFP) > 100 ng/mL at Screening.
• A screening ultrasound suspicious for hepatocellular carcinoma and confirmed with a subsequent CT scan or MRI during the screening period.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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32 participants in 1 patient group

2-DAA + PegIFN/RBV

Experimental group

Description:

2-direct-acting antiviral (2-DAA: ABT-450 \[paritaprevir\] 200 mg once daily \[QD\], ritonavir 100 mg QD, ABT-267 \[ombitasvir\] 25 mg QD) plus pegylated interferon alpha-2a (pegIFN) 180 mcg once weekly and Ribavirin (RBV) weight-based dosing, 1000 to 1200 mg divided twice daily (BID) for 24 weeks (Substudy 1) and followed by pegIFN and RBV alone for an additional 24 weeks (Substudy 2).

Treatment:

Drug: Ribavirin (RBV)

Drug: pegylated interferon alpha-2a (pegIFN)

Drug: ABT-267

Drug: ABT-450/r