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

An Open-Label Study to Evaluate the Safety, Antiviral Activity and Pharmacokinetics of Direct-Acting Antiviral Agent (DAA) Treatment in Combination With Peginterferon Alpha-2a and Ribavirin (pegIFN/RBV) in Chronic Hepatitis C Virus (HCV) Infected Subjects Who Have Experienced Virologic Failure in a Previous AbbVie or Abbott DAA Combination Study

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: ABT-450/r; Drug: ABT-267; Drug: pegylated interferon alpha-2a (pegIFN); Drug: Ribavirin (RBV)

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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).

Drug: ABT-450/r; ABT-450 (tablets) dosed with ritonavir (capsules or tablets); Other Names: ABT-450 also known as paritaprevir and r is also know as ritonavir; Drug: ABT-267; ABT-267 (tablets); Other Names: ABT-267 also known as ombitasvir; Drug: pegylated interferon alpha-2a (pegIFN); pegIFN alpha-2a (syringe); Drug: Ribavirin (RBV); Ribavirin (tablets)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Treatment (SVR12)	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than lower limit of quantitation [LLOQ] 12 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV).	12 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 36 weeks after subject's initial dose of study drug in Substudy 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Virologic Response 24 Weeks Post Treatment (SVR24)	SVR24 was defined as HCV RNA level less than the LLOQ 24 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV).	24 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 48 weeks after subject's initial dose of study drug in Substudy 1
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	eRVR was defined as HCV RNA level < LLOQ at Substudy 1 treatment weeks 4 through 12 without a confirmed HCV RNA >= LLOQ	Treatment weeks 4 through 12 of Substudy 1 (DAAs plus pegIFN alpha-2a and RBV)
Number of Participants With Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after initiation of study drug through 30 days post-DAA dosing. For more details on AEs, see the AE section.	From first dose of study drug through 30 days after last dose of study drug (DAAs plus pegIFN alpha-2a and RBV) (up to 28 weeks).

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2012
• Primary Completion (Actual): May 3, 2017
• Study Completion (Actual): May 3, 2017

Study Registration Dates

• First Submitted: May 30, 2012
• First Submitted That Met QC Criteria: May 30, 2012
• First Posted (Estimate): June 1, 2012

Study Record Updates

• Last Update Posted (Actual): June 19, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: HCV; Chronic Hepatitis C; Hepatitis C Genotype 1; Hepatitis C Virus (HCV)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Interferons; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2; Ritonavir
• Other Study ID Numbers: M13-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No