Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With and Without Ribavirin in Protease-Inhibitors (PI) Failures

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of triple therapy of AbbVie adults with chronic hepatitis C virus (HCV), who have not responded to prior treatment with protease inhibitors. The Triple therapy of AbbVie attacks various sites of the viral genome, thus increasing the potential efficacy of the treatment, especially for patients who have failed PI treatment.

Detailed Description
-----------------
Patients with genotype 1 HCV, who underwent past triple therapy (Telaprevir, Boceprevir or Simeprevir with Pegylated interferon / Ribavirin) and are non-responders, partial responders or in relapse - will be screened in all research centers up to 30 days before the first treatment. At the end of the initial assessment - the recruited participants will be allocated to different treatment groups in accordance with the hepatitis virus subtype 1a, 1b and presence of cirrhosis, as follows: Group A - genotype 1b without cirrhosis - 12 weeks of treatment * Group B - genotype 1b with cirrhosis - 12 weeks of treatment Group C - genotype 1a without cirrhosis - 12 weeks of treatment Group D - genotype 1a with cirrhosis - 24 weeks of treatment (* Only this group will not get Ribavirin) During the treatment period, participants will be asked to describe the treatment's tolerability (in terms of side effects) using self-administered questionnaires: SF-36, and WPAI Hep C v2.0. The follow up will also include physical assessments, side effects documentation, blood tests, abdominal Ultrasound and Fibroscan.

Official Title
-----------------
An Open-label, Multi-center Study to Evaluate Sustained Virologic Response With Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With and Without Ribavirin in Genotype 1 Chronic Hepatitis C Virus Infected Patients With Past PI Failure

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: 12 weeks without Ribavirin
* Drug: 12 weeks with Ribavirin
* Drug: 24 weeks with Ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of hepatitis C, genotype 1A or 1B. Documentation of PI failure of treatment at least 12 months prior to study entry. Patients with cirrhosis - (only patients with cirrhosis Child A with only 5 points). Exclusion Criteria: Inability to stay in the study for 36 weeks. Diagnosis of cross-contamination by HIV or Hepatitis B virus. Renal disfunction (creatinine clearance <30 ml / min). Evidence of hepatic carcinoma. Another serious disease, which may interfere with the study. Pregnant / breast-feeding women. Men with pregnant partners. Drug or alcohol abuse in the six months preceding the study. Chronic liver disease other than hepatitis C (such as Primary biliary cirrhosis, Primary sclerosing cholangitis, Autoimmune hepatitis). Current other treatment for HCV. Past PI Failure due to adverse events. Patients with cirrhosis Child B. Patients with cirrhosis, who were at child B and improved to child A after treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genotype 1b without cirrhosis<br>12 weeks without Ribavirin | Drug: 12 weeks without Ribavirin<br>* 12 weeks Triple Therapy: Ombitasvir, Paritaprevir, Ritonavir (25/150/100 mg dose) once daily and Dasabuvir 250 mg twice daily.<br>* Other names: Triple therapy;|
| Experimental: Genotype 1b with cirrhosis<br>12 weeks with Ribavirin | Drug: 12 weeks with Ribavirin<br>* 12 weeks Triple Therapy: Ombitasvir, Paritaprevir, Ritonavir 25/150/100 mg dose once daily + Dasabuvir 250 mg twice daily + weight adjusted Ribavirin, daily dose: 1,000 mg weight <75 kg, 1,200 mg weight> 75 kg.<br>* Other names: Triple therapy;|
| Experimental: Genotype 1a without cirrhosis<br>12 weeks with Ribavirin | Drug: 12 weeks with Ribavirin<br>* 12 weeks Triple Therapy: Ombitasvir, Paritaprevir, Ritonavir 25/150/100 mg dose once daily + Dasabuvir 250 mg twice daily + weight adjusted Ribavirin, daily dose: 1,000 mg weight <75 kg, 1,200 mg weight> 75 kg.<br>* Other names: Triple therapy;|
| Experimental: Genotype 1a with cirrhosis<br>24 weeks with Ribavirin | Drug: 24 weeks with Ribavirin<br>* 24 weeks Triple Therapy: Ombitasvir, Paritaprevir, Ritonavir 25/150/100 mg dose once daily + Dasabuvir 250 mg twice daily + weight adjusted Ribavirin, daily dose: 1,000 mg weight <75 kg, 1,200 mg weight> 75 kg.<br>* Other names: Triple therapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR (sustained virologic response) rates | Sustained virologic response | 12 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SF (short-form)-36 health survey | psychometrically-based physical and mental health and a preference-based health utility index. | Day 1, weeks 4, 12, 24, 36. | 
| WPAI Hep C v2.0 questionnaire | a scoring manual for work productivity and activity impairment assessment. | Day 1, weeks 4, 12, 24, 36. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis C Virus, Triple Therapy, PI Failure, Genotype 1