A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs Compared With Telaprevir (a Licensed Product) in People With Hepatitis C Virus Infection Who Have Not Had Treatment Before

Study Overview
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Brief Summary
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This is a study to evaluate the efficacy and safety of three experimental drugs compared with telaprevir (a licensed product) in people with hepatitis C virus infection who have not had treatment before.

Detailed Description
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The primary purpose of this study is to demonstrate that treatment with ABT-450/ritonavir (r)/ABT-267 and ABT-333 administered with or without ribavirin (RBV) has non-inferior efficacy compared to treatment with telaprevir and pegylated interferon alpha-2a (pegIFN) and RBV and to compare the safety of these regimens in treatment-naive hepatitis C virus (HCV) genotype (GT) 1a- and 1b-infected adults.

Official Title
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A Randomized, Open-Label Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 and ABT-333 Co-administered With and Without Ribavirin Compared to Telaprevir Co-administered With Pegylated Interferon α-2a and Ribavirin in Treatment-Naïve Adults With Chronic Hepatitis C Genotype 1 Virus Infection (MALACHITE I)

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: Telaprevir
* Drug: Pegylated Interferon alpha 2-a (PegIFN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between 18 and 65 years, inclusive, at time of Screening Females must be post-menopausal for more than 2 years or surgically sterile or practicing abstinence/specific forms of birth control Subject has never received antiviral treatment for hepatitis C infection Chronic HCV Genotype-1 infection prior to study enrollment Exclusion Criteria: Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) Females who are pregnant or plan to become pregnant, or breastfeeding Any current or past clinical evidence of cirrhosis Screening laboratory analyses that showing abnormal laboratory results Use of contraindicated medications within 2 weeks of dosing and subject with contraindication for telaprevir, pegIFN and RBV Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol Positive screen for drugs or alcohol

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: Arm A: 3-DAA + RBV in GT1a<br>ABT-450/r/ABT-267 150 mg/100 mg/25 mg once daily (QD) and ABT-333 250 mg twice daily (BID) and weight-based RBV for 12 weeks (3 direct-acting antivirals [DAAs] with RBV in GT1a) | Drug: ABT-450/r/ABT-267, ABT-333<br>* Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet<br>* Other names: Holkira Pak;Drug: Ribavirin<br>* Tablet<br>|
| Active Comparator: Arm B: TPV/PR in GT1a<br>Telaprevir (TPV) 750 mg every 8 hours (q8h) and pegIFN 180 µg/week and weight-based RBV (PR) for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight-based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1a) | Drug: Ribavirin<br>* Tablet<br>Drug: Telaprevir<br>* Film-coated tablet<br>Drug: Pegylated Interferon alpha 2-a (PegIFN)<br>* Pre-filled syringe<br>|
| Experimental: Arm C: 3-DAA + RBV in GT1b<br>ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID and weight-based RBV for 12 weeks (3 DAAs with RBV in GT1b) | Drug: ABT-450/r/ABT-267, ABT-333<br>* Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet<br>* Other names: Holkira Pak;Drug: Ribavirin<br>* Tablet<br>|
| Experimental: Arm D: 3-DAA in GT1b<br>ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID for 12 weeks (3 DAAs without RBV in GT1b) | Drug: ABT-450/r/ABT-267, ABT-333<br>* Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet<br>* Other names: Holkira Pak;|
| Active Comparator: Arm E: TPV/PR in GT1b<br>Telaprevir 750 mg q8h and pegIFN 180 µg/week and weight-based RBV for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight-based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1b) | Drug: Ribavirin<br>* Tablet<br>Drug: Telaprevir<br>* Film-coated tablet<br>Drug: Pegylated Interferon alpha 2-a (PegIFN)<br>* Pre-filled syringe<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 (SVR12) - Primary Efficacy Analyses | 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. | 12 weeks after the last actual dose of active study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) | SF-36V2 is a generic 36-item questionnaire measuring health-related quality of life (HRQoL) covering 2 summary measures: physical component summary (PCS) and MCS; it consists of 8 subscales. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have choices per item. Scoring is done for both MCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL). | From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E | 
| Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) | SF-36V2 is a generic 36-item questionnaire measuring HRQoL covering 2 summary measures: PCS and MCS; it consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, bodily pain, and general health perception. Participants self-report on items in a subscale that have choices per item. Scoring is done for both PCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL). | From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E | 
| Percentage of Participants With SVR12 - Secondary Efficacy Analyses | The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of active study drug | 
| Percentage of Participants With Virologic Failure During Treatment | Participants in Arms A, C or D demonstrating any of the following were considered virologic failures and discontinued therapy: Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV RNA measurements of >1 log10 IU/mL above nadir) at any time point during treatment Failure to achieve HCV RNA < LLOQ by Week 6 or Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point after HCV RNA < LLOQ during treatment after HCV RNA < LLOQ. Participants in Arms B and E followed virologic stopping criteria described in the TPV Summary of Product Characteristics; they were considered virologic failures and discontinued therapy as follows: HCV RNA > 1000 IU/mL at Week 4 to Week 12, discontinue TPV and pegIFN and RBV HCV RNA > 1000 IU/mL at Week 12, discontinue pegIFN and RBV Confirmed HCV RNA > lower limit of detection (LLOD) at Week 24, discontinue pegIFN and RBV Confirmed HCV RNA > LLOD at Week 36, discontinue pegIFN and RBV. | 12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E | 
| Percentage of Participants With Post-treatment Relapse | Hepatitis C virus (HCV) ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (LLOQ) between the end of treatment and 24 weeks post treatment among participants completing treatment and with HCV RNA less than the LLOQ at the end of treatment. | Within 24 weeks post treatment | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 24 weeks after the last dose of study drug. | 24 weeks after the last actual dose of active study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C, Interferon Free, Hepatitis C Treatment Naive, Hepatitis C Virus, Hepatitis C Genotype 1