The Individualized Management With Pegylated-interferon Alfa-2a (Pegasys) and Ribavirin (Copegus) Offering Viral Eradication: A Study of Pegylated-interferon Alfa-2a Plus Ribavirin in Participants With Chronic Hepatitis C (CHC) Non-genotype 2/3 (IMPROVE)

Study Overview
=================
Brief Summary
-----------------
This study will compare the efficacy and safety of treatment with pegylated-interferon alfa-2a plus ribavirin in participants with non-genotype 2/3 CHC who, after 12 weeks of study treatment, have undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or a greater than or equal to (>=) 2 log10 drop in HCV-RNA. Participants will be randomized to receive pegylated-interferon alfa-2a 180 micrograms subcutaneously weekly plus ribavirin (1000-1400 milligram [mg]) orally daily for the specified duration, followed by 24 weeks of treatment-free follow-up. Participants with detectable HCV-RNA and less than (<) 2 log10 drop in HCV-RNA at week 12 will discontinue therapy.

Official Title
-----------------
The Individualized Management With Pegasys and Ribavirin Offering Viral Eradication (IMPROVE) Trial

Conditions
-----------------
Hepatitis C, Chronic

Intervention / Treatment
-----------------
* Drug: Pegylated-interferon Alfa-2a
* Drug: Ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: evidence of CHC; evidence of hepatitis C non-genotype 2 or 3; compensated liver disease. Exclusion Criteria: infection with HCV genotype 2 or 3; history of having received systemic antiviral therapy with activity against CHC <=3 months prior to start of study; hepatitis A, hepatitis B or human immunodeficiency virus (HIV) infection; history or evidence of a medical condition associated with chronic liver disease other than CHC.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegylated-interferon Alfa-2a + Ribavirin (Group A)<br>Participants with HCV RNA levels greater than (>) 15 international units per milliliter (IU/mL) at Week 4, HCV RNA greater than or equal to (>=) 15 IU/mL at Week 8, and either HCV RNA less than (<) 15 IU/mL or >=2 times logarithmic (2 log10) drop at Week 12, will receive pegylated-interferon alfa-2a (Pegasys) 180 micrograms (mcg) subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 milligrams (mg) orally daily for 48 weeks. | Drug: Pegylated-interferon Alfa-2a<br>* Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.<br>* Other names: Copegus;|
| Experimental: Pegylated-interferon Alfa-2a + Ribavirin (Group B)<br>Participants with HCV RNA levels >15 IU/mL at Week 4, HCV RNA >=15 IU/mL at Week 8, and either HCV RNA <15 IU/mL or >=2 log10 drop at Week 12, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 72 weeks, and ribavirin 1000 to 1400 mg orally daily for 72 weeks. | Drug: Pegylated-interferon Alfa-2a<br>* Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.<br>* Other names: Copegus;|
| Experimental: Pegylated-interferon Alfa-2a + Ribavirin (Group C)<br>Participants with HCV-RNA levels >15 IU/mL at Week 4, and HCV-RNA <15 IU/mL at Week 8, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 36 weeks, and ribavirin 1000 to 1400 mg orally daily for 36 weeks. | Drug: Pegylated-interferon Alfa-2a<br>* Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.<br>* Other names: Copegus;|
| Experimental: Pegylated-interferon Alfa-2a + Ribavirin (Group D)<br>Participants with HCV-RNA levels >15 IU/mL at Week 4, and HCV-RNA <15 IU/mL at Week 8, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. | Drug: Pegylated-interferon Alfa-2a<br>* Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.<br>* Other names: Copegus;|
| Experimental: Pegylated-interferon Alfa-2a + Ribavirin (Group E)<br>Participants with HCV-RNA levels <15 IU/mL at Week 4, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 24 weeks, and ribavirin 1000 to 1400 mg orally daily for 24 weeks. | Drug: Pegylated-interferon Alfa-2a<br>* Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.<br>* Other names: Copegus;|
| Experimental: Pegylated-interferon Alfa-2a + Ribavirin (Group F)<br>Participants with HCV-RNA levels <15 IU/mL at Week 4, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. | Drug: Pegylated-interferon Alfa-2a<br>* Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.<br>* Other names: Copegus;|
| Experimental: Pegylated-interferon Alfa-2a + Ribavirin (Group NR)<br>Participants who do not have any change in HCV-RNA levels at Weeks 4, 8, and 12 will not be randomized (NR) to any of the other groups. Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. | Drug: Pegylated-interferon Alfa-2a<br>* Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.<br>* Other names: Copegus;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B) | SVR was defined as success if the participant had HCV RNA levels <15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups A and B was reported in this analysis. | At 24-week untreated follow-up visit (up to 72 weeks for Group A, up to 96 weeks for Group B) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR (Groups C, D, E, and F) | SVR was defined as success if the participant had HCV RNA levels <15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups C, D, E, and F was reported in this analysis. | At 24-week untreated follow-up visit (up to 60, 72, 48, and 72 weeks for Groups C, D, E, and F, respectively) | 
| Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | End of treatment response (ETR) was defined as Success if the HCV-RNA levels were <15 IU/mL at the end of treatment. Early virological response (EVR) was defined as >=2 log10 decrease in serum HCV RNA or undetectable serum HCV RNA (<15 IU/mL) at Week 12. Complete EVR was defined as Success, if the HCV-RNA levels were <15 IU/mL at Week 12. Partial EVR was defined as Success, if there was a >=2 log10 drop in HCV-RNA at Week 12 compared to baseline but with a level that was still >=15 IU/mL at that time point. | Week 12 (Groups C, D, E, and F), and end of treatment (Weeks 48, 72, 36, 48, 24, and 48 for Groups A, B, C, D, E, and F, respectively) |