Trial Outcomes & Findings for Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected With HCV Genotype 2 or 3 (NCT NCT00056862)
NCT ID: NCT00056862
Last Updated: 2013-12-06
Results Overview
Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
58 participants
Primary outcome timeframe
6 months after stopping therapy
Results posted on
2013-12-06
Participant Flow
Between Dec 2003 and Dec 2004, 31 patients were enrolled into the low-dose group and were treated with peginterferon alfa-2a 90ug/week and ribavirin 400 mg/twice daily for 24 week. From Feb 2005, all subsequent patients were enrolled into a standard-dose group and treated for 24 weeks with the doses of the approved regimen.
Participant milestones
| Measure |
Low Dose Group
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
27
|
|
Overall Study
COMPLETED
|
30
|
27
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Low Dose Group
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected With HCV Genotype 2 or 3
Baseline characteristics by cohort
| Measure |
Low Dose Group
n=30 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=27 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
Total
n=57 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
48 years
n=93 Participants
|
47 years
n=4 Participants
|
48 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
26 participants
n=93 Participants
|
20 participants
n=4 Participants
|
46 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 participants
n=93 Participants
|
5 participants
n=4 Participants
|
7 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
African-American
|
1 participants
n=93 Participants
|
2 participants
n=4 Participants
|
3 participants
n=27 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=93 Participants
|
27 participants
n=4 Participants
|
57 participants
n=27 Participants
|
|
ALT
|
91 U/L
STANDARD_DEVIATION 69 • n=93 Participants
|
97 U/L
STANDARD_DEVIATION 85 • n=4 Participants
|
94 U/L
STANDARD_DEVIATION 77 • n=27 Participants
|
|
HCV RNA
|
6.3 log IU/mL
STANDARD_DEVIATION 0.82 • n=93 Participants
|
5.9 log IU/mL
STANDARD_DEVIATION 1.02 • n=4 Participants
|
6.1 log IU/mL
STANDARD_DEVIATION 0.92 • n=27 Participants
|
|
Genotype
HCV Genotype 2
|
21 participants
n=93 Participants
|
13 participants
n=4 Participants
|
34 participants
n=27 Participants
|
|
Genotype
HCV Genotype 3
|
9 participants
n=93 Participants
|
14 participants
n=4 Participants
|
23 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 6 months after stopping therapyPopulation: Intention-to-treat
Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
Outcome measures
| Measure |
Low Dose Group
n=30 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=27 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Virological Response (Intention to Treat)
Sustained Virological Response (SVR)
|
19 participants
|
21 participants
|
|
Virological Response (Intention to Treat)
Relapse/breakthrough
|
7 participants
|
2 participants
|
|
Virological Response (Intention to Treat)
Nonresponse
|
3 participants
|
1 participants
|
|
Virological Response (Intention to Treat)
Treatment stopped for adverse event
|
0 participants
|
3 participants
|
|
Virological Response (Intention to Treat)
Lost to follow-up
|
1 participants
|
0 participants
|
PRIMARY outcome
Timeframe: 6 months after therapyPopulation: Per protocol
Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
Outcome measures
| Measure |
Low Dose Group
n=28 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=23 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Virological Response Category (Per Protocol)
SVR
|
19 participants
|
20 participants
|
|
Virological Response Category (Per Protocol)
Relapse/breakthrough
|
7 participants
|
2 participants
|
|
Virological Response Category (Per Protocol)
Nonresponse
|
2 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 2 daysThe 1st phase decline is defined as the log difference between baseline HCV RNA level and the level on day 2 of treatment (see Neumann et al, Science, 1998).
Outcome measures
| Measure |
Low Dose Group
n=28 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=23 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
First Phase Decline in Logarithm of HCV RNA Level
|
1.15 logIU/mL
Standard Deviation 0.88
|
2.20 logIU/mL
Standard Deviation 1.14
|
SECONDARY outcome
Timeframe: day 7 to day 28The 2nd phase slope is defined as the slope of the logarithmic viral levels from week 1 to week 4 of treatment (see Neumann et al, Science, 1998).
Outcome measures
| Measure |
Low Dose Group
n=28 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=23 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Slope of Second Phase Decline in HCV Levels
|
1.14 logIU/mL
Standard Deviation 0.69
|
1.39 logIU/mL
Standard Deviation 0.64
|
SECONDARY outcome
Timeframe: 24 weeksTime from treatment initiation to the first negative HCV RNA test during treatment
Outcome measures
| Measure |
Low Dose Group
n=30 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=27 Participants
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Time to Negativity
|
42 days
Interval 32.0 to 51.0
|
28 days
Interval 19.0 to 37.0
|
Adverse Events
Low Dose Group
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Standard Dose Group
Serious events: 3 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low Dose Group
n=30 participants at risk
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=27 participants at risk
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Melanoma and death
|
0.00%
0/30 • 72 weeks
|
3.7%
1/27 • Number of events 1 • 72 weeks
|
|
Cardiac disorders
Mastoiditis complicated by myocardial infarction, heart failure, coronary bypass surgery and death
|
0.00%
0/30 • 72 weeks
|
3.7%
1/27 • Number of events 1 • 72 weeks
|
|
Social circumstances
Heroin overdose leading to death
|
0.00%
0/30 • 72 weeks
|
3.7%
1/27 • Number of events 1 • 72 weeks
|
Other adverse events
| Measure |
Low Dose Group
n=30 participants at risk
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm A receives a lower dose of peginterferon (90 mcg per week) but standard, recommended dose of ribavirin for chronic hepatitis C, genotype 2 and 3.
|
Standard Dose Group
n=27 participants at risk
All patients receive peginterferon alfa-2a and ribavirin for 24 weeks with measurements of HCV RNA, routine liver tests, complete blood counts and side effects at regular intervals during therapy. Arm B receives the standard, recommended dose of peginterferon (180 mcg per week) and standard, recommended dose of ribavirin for chronic hepatitis c, genotype 2 and 3.
|
|---|---|---|
|
Blood and lymphatic system disorders
Sarcoidosis development
|
3.3%
1/30 • Number of events 1 • 72 weeks
|
0.00%
0/27 • 72 weeks
|
|
Cardiac disorders
Atrial fibrillation (off treatment),
|
3.3%
1/30 • Number of events 1 • 72 weeks
|
0.00%
0/27 • 72 weeks
|
|
Blood and lymphatic system disorders
Severe hemolysis requiring transfusion
|
0.00%
0/30 • 72 weeks
|
3.7%
1/27 • Number of events 1 • 72 weeks
|
Additional Information
Jay H. Hoofnagle, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases
Phone: 3014961333
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place