A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs Compared With Telaprevir (a Licensed Product) for Treatment of Chronic Hepatitis C Infection in Treatment-experienced Adults

Phase 3

Completed

• Conditions: Chronic Hepatitis C Infection
• Interventions: Drug: ABT-450/r/ABT-267, ABT-333; Drug: Pegylated Interferon a-2a (PegINF); Drug: Ribavirin; Drug: Telaprevir

• Registration Number: NCT01854528
• Lead Sponsor: AbbVie

Brief Summary

The purpose of this study is to evaluate the safety and antiviral activity of 3 direct-acting antiviral agents (DAAs; ABT-450/ritonavir/ABT-267 \[ABT-450/r/ABT-267; ABT-267 also known as ombitasvir\] and ABT-333 \[also known as dasabuvir\]) plus ribavirin (RBV) compared with telaprevir (TPV) with pegylated interferon/ribavirin (pegIFN/RBV) in patients with chronic hepatitis C virus genotype 1 (HCV GT1) infection without cirrhosis who were previously treated with pegylated interferon/ribavirin (pegIFN/RBV).

Detailed Description

A randomized, open-label, parallel-arm, multicenter study to evaluate the safety and antiviral activity of the 3-DAA regimen (ABT-450/ritonavir/ABT-267 \[ABT-450/r/ABT-267\] and ABT-333) plus ribavirin (3-DAA/RBV) compared with the combination of telaprevir (TPV) with RBV and pegIFN (TPV/RBV) in noncirrhotic participants with chronic hepatitis C virus genotype 1 (HCV GT1) infection who were previously treated with pegylated interferon/ribavirin (pegIFN/RBV).

Participants were randomized in a 2:1 ratio to receive 3-DAA/RBV (ABT-450/r/ABT-267 and ABT-333 plus RBV for 12 weeks) or TPV/RBV (TPV co-administered with pegIFN and RBV for 12 weeks, followed by followed by pegIFN and RBV for either 12 or 36 weeks, per local prescribing information).

Study Timeline

• Study First Submitted: 2013-05-13
• Study First Submitted QC: 2013-05-14
• Study First Posted: 2013-05-15
• Study Start: 2013-06
• Primary Completion: 2014-11
• Study Completion: 2015-07
• Results First Submitted: 2015-11-24
• Results First Submitted QC: 2016-01-14
• Results First Posted: 2016-02-11
• Status Verified: 2016-06
• Last Update Submitted: 2018-05-02
• Last Update Posted: 2018-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 148

Inclusion Criteria

• Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile
• Chronic hepatitis C infection (positive for anti-HCV antibody or HCV RNA at least 6 months before screening and at the time of screening; or positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection)
• Screening laboratory result indicating HCV genotype 1 infection (HCV GT1)
• Participant must have documentation of adherence to a prior pegIFN/RBV combination therapy and meet one of the protocol definitions for treatment failure: null responder, partial responder, relapser
• No evidence of liver cirrhosis

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Exclusion Criteria

• Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody
• Positive screen for drugs or alcohol
• Significant sensitivity to any drug
• Use of contraindicated medications within 2 weeks of dosing
• Abnormal laboratory tests

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TPV/RBV	Pegylated Interferon a-2a (PegINF)	TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously \[SC\] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
3-DAA/RBV	ABT-450/r/ABT-267, ABT-333	3-DAA (ABT-450/r/ABT-267 \[150 mg/ 100 mg/ 25 mg once daily\] and ABT-333 \[250 mg twice daily\]) plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
3-DAA/RBV	Ribavirin	3-DAA (ABT-450/r/ABT-267 \[150 mg/ 100 mg/ 25 mg once daily\] and ABT-333 \[250 mg twice daily\]) plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
TPV/RBV	Ribavirin	TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously \[SC\] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
TPV/RBV	Telaprevir	TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously \[SC\] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment	12 weeks after the last dose of study drug	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline to Final Treatment Visit in the Mental Component Summary (MCS) Score of the Short-Form 36 Health Survey - Version 2 (SF-36v2)	Baseline and Final Treatment Visit (up to Week 12 for 3-DAA/RBV and up to Week 24 or 48 for TPV/RBV)	The SF-36v2 is a general health-related quality of life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises a total of 36 items (questions) targeting a participant's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Domain scores were aggregated into an MCS score (from 0 to 100; a higher score indicates better mental function and well-being).
Mean Change From Baseline to Final Treatment Visit in the Physical Component Summary (PCS) Score of the Short-Form 36 Health Survey - Version 2 (SF-36v2)	Baseline and Final Treatment Visit (up to Week 12 for 3-DAA/RBV and up to Week 24 or 48 for TPV/RBV)	The SF-36v2 is a general health-related quality of life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises a total of 36 items (questions) targeting a participant's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Domain scores were aggregated into a PCS score (range = 0 to 100; a higher score indicates better mental function and well-being).
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment	24 weeks after the last dose of study drug	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 24 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.
Percentage of Participants With Virologic Failure During Treatment	Baseline to end of treatment (12 weeks for 3-DAA/RBV and 24 or 48 weeks for TPV/RBV)	Virologic failure during treatment was defined as HCV ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (≥ LLOQ) after HCV RNA \< LLOQ during treatment or confirmed HCV RNA ≥ LLOQ at the end of treatment.
Percentage of Participants With Virologic Relapse After Treatment	Between end of treatment (Week 12 for 3-DAA/RBV and Week 24 or 48 for TPV/RBV) and Post-treatment (up to Week 12 Post-treatment)	Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (\<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period.