SMV + SOF With/Without RBV for IFN-II Patients With CHC

Study Overview
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Brief Summary
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Prior trials have shown that many G1 CHC patients are ineligible or intolerant to pegylated (PEG)-based regimens due to prior severe side effects, worsening of cytopenias, exacerbation of underlying psychiatric disorders, or autoimmune disorders. These patients will not be candidates for treatment with the approvals of SMV and SOF in early 2014 due to the combination with PEG-regimens. Results of the COSMOS study suggest that these patients are likely to have excellent responses to SMV+SOF with or without RBV with 12 weeks of therapy, and that 24 weeks are unnecessary. This trial is designed to rapidly enroll and be completed in order to confirm this hypothesis.

Official Title
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Simeprevir (SMV) + Sofosbuvir (SOF) With or Without Ribavirin (RBV) for Interferon-intolerant or Ineligible (IFN-II) Patients With Chronic Hepatitis C (CHC)

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Simeprevir
* Drug: Sofosbuvir
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Targeted at least 20% enrollment of patients with cirrhosis Adults >/= age 18 years. Active infection with hepatitis C virus (HCV) genotype 1 Must have health insurance that covers therapy with SOF+RBV Female patients of childbearing age must have a negative pregnancy test prior to initiating therapy, use at least two effective methods of contraception during treatment, and undergo monthly pregnancy tests. Patients must be either IFN-ineligible due to psychiatric, autoimmune, neurological, or other causes that are confirmed appropriate by the PI; OR, IFN-intolerant due to flu-like symptoms, psychiatric problems, cytopenia or other causes deemed appropriate by the PI. Exclusion Criteria: Presence of HIV co-infection Presence of hepatocellular carcinoma (HCC) Prior organ transplantation Any history of hepatic decompensation Patients taking any of the following medications: Anticonvulsants- Carbamazepine, Oxcarbazepine, Phenobarbital, or Phenytoin. Anti-infectives-erythromycin, clarithromycin, or telithromycin. Antifungals- systemic itraconazole, ketoconazole, posaconazole, fluconazole, or voriconazole. Antimycobacterials- rifampin, rifabutin or rifapentine. Corticosteroids- systemic dexamethasone. Propulsives- Cisapride. Herbals- Milk thistle or St. John's Wart. Patients that have been exposed to direct acting anti-viral agents Patients with severe renal impairment (estimated Glomerular Filtration Rate (eGFR) <50 mL/min/1.73m2) or with end stage renal disease (ESRD). Patients with platelet count <50 x109/L, Hemoglobin <10 g/dL, or Neutrophils <0.5 x109/L. Women who are pregnant. Men whose partners are pregnant or plan on becoming pregnant.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SMV+SOF<br>IFN-II patients will receive 12 weeks of OLYSIO (Simeprevir) (150mg QD) + SOVALDI (Sofosbuvir) (400mg QD) | Drug: Simeprevir<br> <br> Drug: Sofosbuvir<br> <br> |
| Active Comparator: SMV+SOF+RBV<br>IFN-II patients will receive 12 weeks of OLYSIO (Simeprevir) (150mg QD) + SOVALDI (Sofosbuvir) (400mg QD) + weight-based Ribavirin 1000-1200 mg/day | Drug: Simeprevir<br> <br> Drug: Sofosbuvir<br> <br> Drug: Ribavirin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Viral Response | Comparison of sustained virologic response at 12 weeks post-treatment (SVR12) in 2 arms of IFN-II patients: one receiving 12 weeks of simeprevir (SMV) (150mg QD)+ sofosbuvir (SOF) (400mg QD) and the second receiving to SMV (150mg QD)+SOF (400mg QD)+weight-based ribavirin (RBV) 1000-1200 mg/day. SVR12 is defined as a patient having undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels 12 weeks post-treatment. Achieving SVR12 is generally indicative of hepatitis C infection being cured. | 12 weeks |