Safety, Tolerability, and Efficacy of 24 Weeks Simeprevir+Sofosbuvir for Chronic Hepatitis C Genotype 1

Study Overview
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Brief Summary
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The goal of this pilot study is to examine both efficacy and tolerability in patients with HCV genotype 1 and mild decompensation with Child-Pugh-Turcott score of 6 or lower. The CPT score is used to assess the prognosis of chronic liver diseases, as well as the required strength and treatment and necessity of liver transplantation. A higher CPT score denotes higher necessity of liver transplantation.

Detailed Description
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Key objectives of this study include: To describe efficacy (SVR) in a special population of patients with chronic hepatitis C who are not willing or not candidates for IFN-based therapy. To describe safety, tolerability, and treatment persistency in this patient population with advanced liver disease.

Official Title
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Safety, Tolerability, and Efficacy of Simeprevir 150 mg Daily Plus Sofosbuvir 400 mg Daily for 24 Weeks in Patients With Chronic Hepatitis C Genotype 1 With CPT Score of 6 or Lower Who Are IFN-Intolerant or Unwilling to be Treated With IFN

Conditions
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PT-NANBH

Intervention / Treatment
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* Drug: Simeprevir
* Drug: Sofosbuvir


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult 18-72 years Cirrhosis: defined by stage 4 on biopsy or noninvasive tests or presence of splenomegaly and platelet of 130K or lower, or presence of shrunken nodular liver on CT or MRI, or presence of varices or encephalopathy or ascites. HCV genotype 1 or indeterminate and later assessed at Screening and confirmed as genotype 1 Exclusion criteria: Uncontrolled ascites, uncontrolled hepatic encephalopathy, or uncontrolled esophageal/gastric varices Co-infection with HIV or hepatitis B (HBV) CPT 7 or above, or MELD >10 Total bilirubin 4.0 mg/dL or above CrCl (creatinine clearance) < 30 mL/min Any unstable active medical illnesses. Active use of illicit substances, alcohol, or smoking. Any malignancy within last 5 years except for basal cell skin cancer that has been adequately treated or HCC within Milan or UCSF criteria, which will be acceptable Any prior treatment with direct acting antivirals (approved or investigational), including HCV protease inhibitors, such as SMV. Patients who received prior treatment with SOF, and/or NS5A inhibitors (e.g. ledipasvir or Daclatasvir) can be included in this study Platelet < 30 K/uL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 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: Simeprevir + sofosbuvir daily, 24 weeks<br>Eligible and consenting patients will be treated with sofosbuvir (SOF) 400 mg daily and simeprevir (SMV) 150 mg daily for 24 weeks. Both drugs will be administered orally, per manufacturers' instructions. | Drug: Simeprevir<br> <br> * Other names: Olysio;Drug: Sofosbuvir<br> <br> * Other names: Sovaldi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virologic response (SVR) HCV RNA PCR <25 IU/mL 12 weeks post-treatment |  | 12 weeks after end of treatment or virologic response after liver transplantation, whichever comes first, assessed up to 12 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious adverse events, adverse events grade 3 and above |  | 24 weeks while on treatment and 24 weeks after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis C, liver transplantation, genotype 1