SWITCH-1: Switching Regimen in Treating Cirrhotic HCV GT1b Subjects
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PR4 + LDV/SOF + ASV 4 wk 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
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.
Other Names:
|
| Experimental: PR4 + LDV/SOF + SMV 4 wk 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
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.
Other Names:
|
| Experimental: PR4 + LDV/SOF + ASV 6 wk 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
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.
Other Names:
|
| Experimental: PR4 + LDV/SOF + SMV 6 wk 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
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.
Other Names:
|
| Experimental: PR4 + LDV/SOF + ASV 8 wk 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
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.
Other Names:
|
| Experimental: PR4 + LDV/SOF + SMV 8 wk 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
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.
Other Names:
|
| Experimental: PR4 + LDV/SOF + ASV 12 wk 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
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.
Other Names:
|
| Experimental: PR4 + LDV/SOF + SMV 12 wk 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
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of participants with sustained virologic response 12 weeks (SVR12) after discontinuation of therapy [Post treatment Week 12]
SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after last dose of study drug.
- Proportion of participants with adverse events leading to permanent discontinuation of study drug(s) [Baseline up to Week 24]
Secondary Outcome Measures
- Proportion of participants with unquantifiable HCV viral load at specified time points during and after treatment [Baseline up to Week 24]
- Treatment adherence [Baseline to Week 12]
To evaluate the proportion of patients adherent to therapy (both on-treatment adherence and treatment discontinuation)
- Change in health related quality of life evaluated with questionnaires [Up to Posttreatment Week 24]
To evaluate the change in health-related quality of life during and after treatment with questionnaires
- Change in mental health evaluated with questionnaires [Up to Posttreatment Week 24]
To evaluate the change in mental health during and after treatment with questionnaires
- Liver disease progression [Up to 10 years]
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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Liver Fibrosis Diagnosis and Treatment Centre, 302 Hospital | Beijing | Beijing | China | 100039 |
| 2 | Humanity and Health GI and Liver Centre | Hong Kong | Hong Kong | China | 00852 |
Sponsors and Collaborators
- Humanity and Health Research Centre
- Beijing 302 Hospital
- Nanfang Hospital of Southern Medical University
Investigators
- Principal Investigator: George Lau, Humanity and Health GI and Liver Centre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H&H_SWITCH-1