Back to resultsThe 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) (IMPROVE)
Primary Purpose
Hepatitis C, Chronic
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pegylated-interferon Alfa-2a
Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Pegylated-interferon Alfa-2a + Ribavirin (Group A)
Pegylated-interferon Alfa-2a + Ribavirin (Group B)
Pegylated-interferon Alfa-2a + Ribavirin (Group C)
Pegylated-interferon Alfa-2a + Ribavirin (Group D)
Pegylated-interferon Alfa-2a + Ribavirin (Group E)
Pegylated-interferon Alfa-2a + Ribavirin (Group F)
Pegylated-interferon Alfa-2a + Ribavirin (Group NR)
Arm Description
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.
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.
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00483938
Brief Title
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)
Acronym
IMPROVE
Official Title
The Individualized Management With Pegasys and Ribavirin Offering Viral Eradication (IMPROVE) Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
236 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pegylated-interferon Alfa-2a + Ribavirin (Group A)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pegylated-interferon Alfa-2a + Ribavirin (Group B)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pegylated-interferon Alfa-2a + Ribavirin (Group C)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pegylated-interferon Alfa-2a + Ribavirin (Group D)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pegylated-interferon Alfa-2a + Ribavirin (Group E)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pegylated-interferon Alfa-2a + Ribavirin (Group F)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pegylated-interferon Alfa-2a + Ribavirin (Group NR)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pegylated-interferon Alfa-2a
Other Intervention Name(s)
Pegasys
Intervention Description
Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
Copegus
Intervention Description
Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B)
Description
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.
Time Frame
At 24-week untreated follow-up visit (up to 72 weeks for Group A, up to 96 weeks for Group B)
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR (Groups C, D, E, and F)
Description
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.
Time Frame
At 24-week untreated follow-up visit (up to 60, 72, 48, and 72 weeks for Groups C, D, E, and F, respectively)
Title
Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F)
Description
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.
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53210
Country
United States
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5H 4B9
Country
Canada
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2X8
Country
Canada
City
Abbotsford
State/Province
British Columbia
ZIP/Postal Code
V2S 3N5
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
City
Vernon
State/Province
British Columbia
ZIP/Postal Code
V1T 1W9
Country
Canada
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8V 3P9
Country
Canada
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
City
East York
State/Province
Ontario
ZIP/Postal Code
M4C 3E7
Country
Canada
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5G2
Country
Canada
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5M 4N4
Country
Canada
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1L7
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada
City
Woodbridge
State/Province
Ontario
ZIP/Postal Code
L4L 4Y7
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
22050141
Citation
Lee SS, Sherman M, Ramji A, Greenbloom S, Elkashab M, Pluta H, Hilzenrat N, Balshaw R, Usaty C, Myers RP. Randomised clinical trial: the efficacy of treatment, guided by a shorter duration of response, using peginterferon alfa-2a plus ribavirin for hepatitis C virus other than genotypes 2 or 3. Aliment Pharmacol Ther. 2012 Jan;35(1):37-47. doi: 10.1111/j.1365-2036.2011.04911.x. Epub 2011 Nov 2.
Results Reference
derived
Learn more about this trial
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)
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