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

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Randomized, Open-Labeled Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 and ABT-333 Co-administered With Ribavirin Compared to Telaprevir Co-administered With Pegylated Interferon a-2a and Ribavirin in Treatment-Experienced Adults With Chronic Hepatitis C Genotype 1 Virus Infection (MALACHITE-II)

Conditions
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Chronic Hepatitis C Infection

Intervention / Treatment
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* Drug: ABT-450/r/ABT-267, ABT-333
* Drug: Ribavirin
* Drug: Pegylated Interferon a-2a (PegINF)
* Drug: Telaprevir


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3-DAA/RBV<br>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. | Drug: ABT-450/r/ABT-267, ABT-333<br>* Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet<br>* Other names: Viekira PAK;Drug: Ribavirin<br>* Tablet<br>|
| Active Comparator: TPV/RBV<br>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. | Drug: Ribavirin<br>* Tablet<br>Drug: Pegylated Interferon a-2a (PegINF)<br>* Pre-filled syringe<br>Drug: Telaprevir<br>* Film-coated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment | 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. | 12 weeks after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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). | Baseline and Final Treatment Visit (up to Week 12 for 3-DAA/RBV and up to Week 24 or 48 for TPV/RBV) | 
| 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) | 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). | Baseline and Final Treatment Visit (up to Week 12 for 3-DAA/RBV and up to Week 24 or 48 for TPV/RBV) | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment | 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. | 24 weeks after the last dose of study drug | 
| Percentage of Participants With Virologic Failure During Treatment | 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. | Baseline to end of treatment (12 weeks for 3-DAA/RBV and 24 or 48 weeks for TPV/RBV) | 
| Percentage of Participants With Virologic Relapse After 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. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapser, Partial responder, Interferon free, Treatment-experienced, Hepatitis C Virus, Null responder, Hepatitis C Genotype 1, paritaprevir, ombitasvir, dasabuvir, ribavirin, Viekira PAK, Chronic hepatitis C