Clinical trial NCT01609933: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C Virus (HCV)
Hepatitis C Genotype 1
Chronic Hepatitis C
HCV
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-06-01
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 71
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
timeFrame: 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 outcomes:
measure: Percentage of Participants Achieving Virologic Response 24 Weeks Post Treatment (SVR24)
timeFrame: 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
measure: Percentage of Participants With Extended Rapid Virologic Response (eRVR)
timeFrame: Treatment weeks 4 through 12 of Substudy 1 (DAAs plus pegIFN alpha-2a and RBV)
measure: Number of Participants With Adverse Events
timeFrame: 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).
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.