Understanding HCV Reinfection Rates in an Incarcerated Population After Cure With Interferon Free HCV Treatment

Study Overview
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Brief Summary
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This pilot study is crucial to determining whether treating individuals who are at high risk for transmission or re-infection will impact HCV reinfection rates. It will establish the feasibility of DAA treatment in corrections facilities, as well as delineate the underlying immune basis of HCV cure and reinfection.

Official Title
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Understanding HCV Reinfection Rates in an Incarcerated Population After Cure With Interferon Free HCV Treatment: A Pilot Project

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: Paritaprevir
* Drug: Ritonavir
* Drug: Dasabuvir
* Drug: Ombitasvir
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An offender at the PEI Provincial Correction Centre during the enrollment time Male, 18 -70 years of age, inclusive, at time of screening Chronic HCV genotype 1 infection HCV infection, as demonstrated by positive HCV immunosorbant assay and detectable HCV viral load No evidence of decompensated liver disease (refractory ascites, variceal bleed within 1 year, active hepatic encephalopathy or Child-Pugh score greater than 6) HIV negative Males must be abstinent from sexual intercourse, surgically sterile or agree to practice two effective forms of birth control from those listed below, throughout the course of the study, starting with Study Day 1 and for 7 months after the last dose of study drug (or per local RBV label): Partner(s) using an IUD (intrauterine device), Partner(s) using oral, injected, or implanted methods of hormonal contraceptives, Subject and/or partner(s) using condoms, contraceptive sponge, or diaphragm with spermicidal jellies or creams. Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements Must voluntarily sign and date an informed consent form, approved by a Research Ethics Board prior to the initiation of any screening or study specific procedures Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any drug Positive test result at screening for Hepatitis B surface antigen Prior therapy with direct acting antivirals for the treatment of HCV Evidence of decompensated liver disease (current or past refractory ascites, variceal bleed within 1 year, active hepatic encephalopathy) HIV positive screening test Unwilling to follow up for 48 weeks after treatment completion Use of any herbal supplements (including milk thistle) within 2 weeks or 10 half-lives of the respective supplement, whichever is longer, prior to the first dose of study drug HCV genotype performed during screening indicating unable to genotype or co-infection with any other HCV genotype Use of any medications contraindicated for use with the study regimen Clinically significant abnormalities, other than HCV-infection, based upon the results of a medical history, physical examination, vital signs, and laboratory profile that make the subject an unsuitable candidate for this study in the opinion of the investigator Serum Alpha-Fetoprotein (AFP) > 200 ng/mL at screening Any cause of liver disease other than chronic HCV-infection, including but not limited to the following: Hemochromatosis Alpha-1 antitrypsin deficiency Wilson's disease Autoimmune hepatitis Alcoholic liver disease Nonalcoholic steatohepatitis Drug-related liver disease Screening laboratory analyses showing any of the following abnormal laboratory results: ALT > 5 × upper limit of normal (ULN) Aspartate aminotransferase (AST) > 5 × ULN Calculated creatinine clearance (using Cockcroft-Gault method) < 60 mL/min Albumin 25 g/L Prothrombin time/International normalized ratio (INR) > 2.3. Hemoglobin < LLN Platelets < 60,000 cells per mm3 Absolute neutrophil count (ANC) < 1500 cells/μL Total bilirubin ≥ 51 umol/L History of solid organ transplantation. Receipt of any investigational product within a time period equal to 10 half-lives of the product, if known, or a minimum of 6 weeks prior to study drug administration. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive paritaprevir, dasabuvir, ombitasvir, ritonavir and/or RBV. Current enrollment in another clinical study, prior enrollment in this study, or previous exposure to paritaprevir, ombitasvir, or dasabuvir. Concurrent participation in a non-interventional, epidemiologic or registry trials may be permitted with approval of the principal investigator. The use of colony stimulating factors, such as granulocyte colony stimulating factor (GCSF) or erythropoietin within 2 months of the screening period. Uncontrolled clinically significant cardiac, respiratory (except mild asthma), hepatic, gastrointestinal, hematologic or psychiatric disease or disorder, or any uncontrolled medical illness, which is unrelated to the hepatic disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Other: HCV Genotype 1, with and without cirrhosis<br> | Drug: Paritaprevir<br> <br> Drug: Ritonavir<br> <br> Drug: Dasabuvir<br> <br> Drug: Ombitasvir<br> <br> Drug: Ribavirin<br>* In genotype 1b individuals without cirrhosis, treatment will NOT include ribavirin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Re-infection rate in individuals treated with DAA therapy | This will require HCV quasispecies determination at baseline and in potentially re-infected individuals. Re-infection will require demonstration of HCV RNA above level of detection after SVR12 with a phyogenetically distinct HCV species. | 1 year following treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with sustained virologic response at 12 weeks post treatment |  | 12 Weeks post treatment | 
| Change in fibrosis measured by transient elastography |  | From day 0 to the end of follow-up | 
| Global and HCV-specific T cell function before and after treatment with DAA therapy. |  | From day 0 to end of follow-up | 
| Global and HCV-specific B cell function before and after treatment with DAA therapy. |  | From day 0 to end of follow-up | 
| Global and HCV-specific NK cell function before and after treatment with DAA therapy. |  | From day 0 to end of follow-up |