Switching Regimen in Treating Cirrhotic HCV GT1b Subjects

Study Overview
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Brief Summary
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This is a prospective, randomized study to evaluate the efficacy and safety of switching treatment from Peg-interferon and Ribavirin to direct-acting antiviral agents in Chinese with CHC genotype 1b infection, who are interferon/ribavirin-intolerant.

Official Title
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Efficacy and Safety of Switching From Pegylated Interferon/Ribavirin (PR) to Direct-acting Antiviral Agents (DAAs) for Chinese With CHC Genotype 1b Infection (SWITCH-1)

Conditions
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Chronic Hepatitis C Infection

Intervention / Treatment
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* Drug: PR4 + LDV/SOF + ASV 4 wk
* Drug: PR4 + LDV/SOF + SMV 4 wk
* Drug: PR4 + LDV/SOF + ASV 6 wk
* Drug: PR4 + LDV/SOF + SMV 6 wk
* Drug: PR4 + LDV/SOF + ASV 8 wk
* Drug: PR4 + LDV/SOF + SMV 8 wk
* Drug: PR4 + LDV/SOF + ASV 12 wk
* Drug: PR4 + LDV/SOF + SMV 12 wk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with chronic HCV GT1b infection; HCV RNA ≥ 10000 IU/mL at screening; Received 4 weeks pegylated interferon plus ribavirin (PR4) therapy and are intolerant to PR4; Cirrhosis determination; a liver biopsy may be required; Use of highly effective contraception methods if female of childbearing potential or sexually active male; Exclusion Criteria: Pregnant or nursing female or male with pregnant female partner; HIV or HBV co-infection; Hematologic or biochemical parameters at Screening outside the protocol- specified requirements; Active or recent history (≤ 1 year) of drug or alcohol abuse; History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: PR4 + LDV/SOF + ASV 4 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA <25 IU/ml by week 2 will receive LDV/SOF + ASV for 4 weeks. | Drug: PR4 + LDV/SOF + ASV 4 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Asunaprevir (ASV) 200mg administered orally twice daily.<br>* Other names: Sunvepra®;|
| Experimental: PR4 + LDV/SOF + SMV 4 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA <25 IU/ml by week 2 will receive LDV/SOF + SMV for 4 weeks. | Drug: PR4 + LDV/SOF + SMV 4 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Simeprevir (SMV) 150 mg tablet orally once daily.<br>* Other names: OLYSIO®;|
| Experimental: PR4 + LDV/SOF + ASV 6 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA <25 IU/ml by week 4 will receive LDV/SOF + ASV for 6 weeks. | Drug: PR4 + LDV/SOF + ASV 6 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Asunaprevir (ASV) 200mg administered orally twice daily.<br>* Other names: Sunvepra®;|
| Experimental: PR4 + LDV/SOF + SMV 6 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA <25 IU/ml by week 4 will receive LDV/SOF + SMV for 6 weeks. | Drug: PR4 + LDV/SOF + SMV 6 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Simeprevir (SMV) 150 mg tablet orally once daily.<br>* Other names: OLYSIO®;|
| Experimental: PR4 + LDV/SOF + ASV 8 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA > 2 log drop but ≥25 IU/ml by week 4 will receive LDV/SOF + ASV for 8 weeks. | Drug: PR4 + LDV/SOF + ASV 8 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Asunaprevir (ASV) 200mg administered orally twice daily.<br>* Other names: Sunvepra®;|
| Experimental: PR4 + LDV/SOF + SMV 8 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA > 2 log drop but ≥25 IU/ml by week 4 will receive LDV/SOF + SMV for 8 weeks. | Drug: PR4 + LDV/SOF + SMV 8 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Simeprevir (SMV) 150 mg tablet orally once daily.<br>* Other names: OLYSIO®;|
| Experimental: PR4 + LDV/SOF + ASV 12 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA <2 log drop by week 4 will receive LDV/SOF + ASV for 12 weeks. | Drug: PR4 + LDV/SOF + ASV 12 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Asunaprevir (ASV) 200mg administered orally twice daily.<br>* Other names: Sunvepra®;|
| Experimental: PR4 + LDV/SOF + SMV 12 wk<br>Participants treated with 4 weeks pegylated interferon and ribavirin and plasma HCV RNA <2 log drop by week 4 will receive LDV/SOF + SMV for 12 weeks. | Drug: PR4 + LDV/SOF + SMV 12 wk<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Ribavirin (RBV) administered as a tablet orally according to body weight (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Ledipasvir/sofosbuvir (LDV/SOF) 90 mg/400 mg fixed dose combination (FDC) tablet administered orally once daily; Simeprevir (SMV) 150 mg tablet orally once daily.<br>* Other names: OLYSIO®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with sustained virologic response 12 weeks (SVR12) after discontinuation of therapy | SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after last dose of study drug. | Post treatment Week 12 | 
| Proportion of participants with adverse events leading to permanent discontinuation of study drug(s) |  | Baseline up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with unquantifiable HCV viral load at specified time points during and after treatment |  | Baseline up to Week 24 | 
| Treatment adherence | To evaluate the proportion of patients adherent to therapy (both on-treatment adherence and treatment discontinuation) | Baseline to Week 12 | 
| Change in health related quality of life evaluated with questionnaires | To evaluate the change in health-related quality of life during and after treatment with questionnaires | Up to Posttreatment Week 24 | 
| Change in mental health evaluated with questionnaires | To evaluate the change in mental health during and after treatment with questionnaires | Up to Posttreatment Week 24 | 
| Liver disease progression | Liver disease progression is a composite endpoint measured by laboratory parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin, platelets, prothrombin time (PT) and α-fetoprotein) and observed or reported clinical signs and symptoms. | Up to 10 years |