A Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/r With or Without Dasabuvir and With or Without Ribavirin in Chronic Hepatitis C Virus Genotype 1 or 4 Infected Adults With Successfully Treated Early Stage Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r), with or without dasabuvir (DSV) coadministered with or without ribavirin (RBV) for 12 or 24 weeks in adult patients with genotype 1 or genotype 4 chronic HCV infection and treated early stage Hepatocellular Carcinoma with compensated cirrhosis.

Official Title
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Open-label Study to Evaluate the Safety and Efficacy of the Combination of Ombitasvir, Paritaprevir/r ± Dasabuvir With or Without Ribavirin (RBV) in Adult Patients With GT1 or GT4 Chronic HCV Infection and Response to Prior Treatment of Early Stage Hepatocellular Carcinoma (GEODE - I)

Conditions
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Chronic Hepatitis C Infection

Intervention / Treatment
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* Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir
* Drug: ombitasvir/paritaprevir/ritonavir
* Drug: ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, at least 18 years of age at time of screening Chronic hepatitis C virus (HCV) infection prior to study enrollment with screening laboratory results indicating HCV genotype 1 or 4 infection Early stage hepatocellular carcinoma (HCC) diagnosed based on the typical hallmark of HCC (hypervascular in the arterial phase with washout in the portal venous or delayed phases) Compensated cirrhosis defined as a Child-Pugh score of 5 or 6 at Screening • A minimal rim of ascites if detected at imaging is acceptable. Exclude ascites that requires the need to apply diuretic treatment to control ascites Documented complete response to HCC treatment. Females must be post-menopausal for more than 2 years or surgically sterile or practicing acceptable forms of birth control. Exclusion Criteria: Use of known strong or moderate inducers of cytochrome P450 3A (CYP3A) in participants receiving ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) with and without dasabuvir (DSV), strong inducers and inhibitors (e.g., gemfibrozil) of cytochrome P450 2C8 (CYP2C8) in participants receiving OBV/PTV/r with DSV, medications contraindicated for ritonavir or RBV (for those that receive RBV) within 2 weeks or 10 half-lives (if known), whichever is longer, prior to study drug . For medications contraindicated with AbbVie's 2-direct-acting antiviral agent (2-DAA) and 3-DAA regimen, refer to the recommended prescribing information section of the approved local product labels. Positive test result for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab). Patients regardless of eligibility to liver transplant, who have a comorbid disease that might preclude completion of study follow-up. Clinically significant abnormalities, other than HCV infection, in a participant with HCC based upon the medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG) that make the participant an unsuitable candidate for this study in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OBV/PTV/r ± DSV ± RBV for 12 or 24 weeks<br>OBV/PTV/r (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily]) with or without dasabuvir (250 mg twice daily) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks, dosed as per label based on HCV genotype/subtype and presence of cirrhosis. | Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir<br>* Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet<br>* Other names: dasabuvir also known as ABT-333;Drug: ombitasvir/paritaprevir/ritonavir<br>* Tablet; ombitasvir coformulated with paritaprevir and ritonavir<br>* Other names: ombitasvir also known as ABT-267;Drug: ribavirin<br>* 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 Post-treatment (SVR12) | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug. Participants with missing data after flanking imputation were imputed as nonresponders. | 12 weeks after the last actual dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ throughout treatment with at least 6 weeks of treatment. | Baseline (Day 1) and Treatment Weeks 2, 4, 8, 12 (end of treatment for 12-week treatment), 16, 20 and 24 (end of treatment for 12-week treatment) | 
| Percentage of Participants With Post-treatment Relapse | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment. | From the end of treatment through 12 weeks after the last dose of study drug | 
| Percentage of Participants With Long Term Clinical Outcomes | The percentage of participants with long term clinical outcomes (de novo hepatocellular carcinoma (HCC) lesions, liver decompensation, unexpected liver transplant, liver related death, or any of the above) from first dose of study drug through 24 weeks post-treatment follow-up. | up to 48 weeks | 
| Percentage of Participants With Recurrent HCV Infection Post Liver Transplant | The percentage of participants with recurrent HCV infection post liver transplant out of all participants with liver transplant during the study. | from liver transplant to 24 weeks post-treatment (up to 48 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C Infection, Early Stage Hepatocellular Carcinoma