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

NCT ID: NCT01609933

Last Updated: 2018-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-18
• Study Completion Date: 2017-05-03

Brief Summary

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.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

2-DAA + PegIFN/RBV

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).

Group Type: EXPERIMENTAL

ABT-450/r

Intervention Type: DRUG

ABT-450 (tablets) dosed with ritonavir (capsules or tablets)

ABT-267

Intervention Type: DRUG

ABT-267 (tablets)

pegylated interferon alpha-2a (pegIFN)

Intervention Type: DRUG

pegIFN alpha-2a (syringe)

Ribavirin (RBV)

Intervention Type: DRUG

Ribavirin (tablets)

Interventions

ABT-450/r

ABT-450 (tablets) dosed with ritonavir (capsules or tablets)

Intervention Type: DRUG

ABT-267

ABT-267 (tablets)

Intervention Type: DRUG

pegylated interferon alpha-2a (pegIFN)

pegIFN alpha-2a (syringe)

Intervention Type: DRUG

Ribavirin (RBV)

Ribavirin (tablets)

Intervention Type: DRUG

Other Intervention Names

ABT-450 also known as paritaprevir and r is also know as ritonavir; ABT-267 also known as ombitasvir

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 71 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

References

Bernstein D, Tripathi R, Cohen DE. Ombitasvir, paritaprevir, and ritonavir with peginterferon-alpha2a plus ribavirin in treatment-experienced patients with chronic hepatitis C virus genotype 1 infection. Hepat Med. 2019 Feb 13;11:35-40. doi: 10.2147/HMER.S189158. eCollection 2019.

Reference Type: DERIVED

PMID: 30858739 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

M13-101

Identifier Type: -

Identifier Source: org_study_id