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)

Phase 3

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: Pegylated-interferon Alfa-2a; Drug: Ribavirin

• Registration Number: NCT00483938
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06
• Study First Submitted: 2007-06-07
• Study First Submitted QC: 2007-06-07
• Study First Posted: 2007-06-08
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2016-11
• Results First Submitted: 2016-11-25
• Results First Submitted QC: 2016-11-25
• Last Update Submitted: 2016-11-25
• Results First Posted: 2017-01-23
• Last Update Posted: 2017-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 236

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pegylated-interferon Alfa-2a + Ribavirin (Group A)	Pegylated-interferon Alfa-2a	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group B)	Pegylated-interferon Alfa-2a	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group C)	Pegylated-interferon Alfa-2a	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group E)	Pegylated-interferon Alfa-2a	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group NR)	Pegylated-interferon Alfa-2a	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group D)	Pegylated-interferon Alfa-2a	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group F)	Pegylated-interferon Alfa-2a	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group A)	Ribavirin	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group B)	Ribavirin	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group D)	Ribavirin	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group C)	Ribavirin	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group E)	Ribavirin	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group F)	Ribavirin	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.
Pegylated-interferon Alfa-2a + Ribavirin (Group NR)	Ribavirin	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B)	At 24-week untreated follow-up visit (up to 72 weeks for Group A, up to 96 weeks for Group 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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With SVR (Groups C, D, E, and F)	At 24-week untreated follow-up visit (up to 60, 72, 48, and 72 weeks for Groups C, D, E, and F, respectively)	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.
Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F)	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)	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.