Ignite Creation Date:
2024-05-05 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00502099
Status:
COMPLETED
Last Update Posted:
2012-10-23
First Post:
2007-07-15
Brief Title:
Comparison of Pegasys Versus Peg-Intron for Treatment of Chronic Hepatitis C Genotype 4
Sponsor:
Amr Hafez
Organization:
Ain Shams University
Study Overview
Official Title:
Phase 4 Comparative Study of Pegasys vs Peg-Intron for Treatment of Chronic Hepatitis C Genotype 4
Status:
COMPLETED
Status Verified Date:
2012-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Genotype 4 hepatitis C virus is the cause of approximately 20 of the 170 million cases of chronic hepatitis C in the world Although rare in western nations genotype 4 is the most common variant of the hepatitis C virus in Egypt and is also found throughout Africa and the Middle East Early reports on the treatment of patients with genotype 4 chronic hepatitis C with interferon-alfa IFN-alfa monotherapy indicate poor rates of sustained viral response SVR With the introduction of ribavirin combination therapy and with pegylation of the IFN alfa molecule however response rates have improved dramatically and current clinical trial data indicate that SVR rates between 43 and 79 are attainable in genotype 4 patients who are receiving pegylated IFN alfa plus ribavirin for 48 weeks Clinical advances to optimize treatment for each patient have also been made and tailored treatment options are now being developed that are comparable to the treatment approaches for genotype 1 2 and 3 patients A treatment duration of between 36 and 48 weeks appears to be optimal for most patients with chronic hepatitis C genotype 4The aim of this study is to assess the efficacy and safety of pegylated interferon alpha 2a in patients with chronic hepatitis C genotype 4 in comparison to a historical cohort of patients treated with pegylated interferon alpha 2b
Detailed Description:
The treatment of chronic hepatitis C with interferon IFN-based medicines has advanced steadily since publication of the first clinical trials in the late 1980sInitial interventions using IFN-alfa monotherapy achieved limited success but the introduction of IFN-alfa plus ribavirin combination therapy and the pegylation of the IFN alfa molecule which improved pharmacokinetics and simplified dosing regimens resulted in a steady improvement in overall treatment outcomes Sustained virologic responses SVR defined as undetectable HCV RNA 24 weeks after completing treatment have increased from 6 with IFN alfa monotherapy to more than 50 with pegylated interferon alfa PEG-IFN alfa plus ribavirin regimensObservations specific to genotype 4 chronic hepatitis C have followed a similar path with initial investigations of IFN-alfa monotherapy producing limited success These studies found that IFN-alfa monotherapy which is usually administered at a dose of 3-5 MIU three times a week for six months resulted in an SVR in only 5-25 of treated patients24-26 The subsequent inclusion of ribavirin in treatment regimens had a dramatic improvement on SVR attainment with rates of 8 and 42 reported for patients receiving IFN-alfa alone and in combination with ribavirin 1000-1200 mgday respectively
Pegylation of the IFN alfa molecule was the next major advance in the treatment of genotype 4 chronic hepatitis CAlthough two early studies failed to demonstrate a significant difference in SVR rates between PEG-IFN alfa-2b plus ribavirin and native IFN alfa-2b plus ribavirin eg 429 vs 323 p 04327 subsequent investigations reported SVR rates of 50 to 79 in patients receiving PEG-IFN alfa-2b plus ribavirin 800-1200 mgday for 48 weeks Overall meta-analysis of clinical trial data shows that SVR rates are significantly higher among genotype 4 patients receiving PEG-IFN alfa plus ribavirin than in those receiving IFN-alfa plus ribavirin 55 vs 30 p 0008833 This analysis also confirms the importance of adequate ribavirin dosing with higher SVR rates in patients receiving PEG-IFN alfa in combination with high-dose 1000-1200 mgday and low-dose 800 mgday ribavirin 720 and 458 respectively p value not presented The importance of ribavirin dosing in genotype 4 patients with chronic hepatitis C is also demonstrated in an analysis of the genotype 4 patients included in the registration studies for PEG-IFN alfa-2a22 34 In this analysis SVR rates were 79 among patients receiving PEG-IFN alfa-2a 180 mcgweek plus ribavirin 1000-1200 mgday for 48 weeks compared with 63 in those receiving the same regimen plus a lower dose of ribavirin 800 mgdayThe optimization of treatment duration is critical in ensuring that SVR rates are maximized without exposing the patient to an unnecessarily long treatment regimen that may have unfavorable implications in terms of cost and tolerability The question of optimal treatment duration for genotype 4 chronic hepatitis C was addressed in a prospective randomized study in which patients received PEG-IFN alfa-2b 15 mcgkgweek plus ribavirin 1000-1200 mgday for 24 36 or 48 weeksOverall SVR rates were significantly higher in patients receiving treatment for 36 or 48 weeks than in those treated for 24 weeks 66 and 69 vs 29 p 0001 for each comparison Fig 2 Relapse appeared to be a major factor in determining treatment outcomes virologic relapse during follow-up was highest among patients treated for 24 weeks 20 of 45 44 but relatively rare among the longer treatment arms
There was no significant difference between the 36-week and 48-week treatment regimens for the overall cohort However among patients with baseline viral load 2 million copiesmL who attained SVR 65 were treated for 48 weeks and 35 were treated for 36 weeks all patients with high baseline viral load treated for 24 weeks failed to attain SVR This suggests that the 48-week treatment regimen may be better suited to patients with high baseline viremia The efficacy and safety of pegylated interferon 2a has not be adequately evaluated in chronic hepatitis C genotype 4 patients in well conducted clinical trials involving well characterized cohorts and long follow up
Pegylation of the IFN alfa molecule was the next major advance in the treatment of genotype 4 chronic hepatitis CAlthough two early studies failed to demonstrate a significant difference in SVR rates between PEG-IFN alfa-2b plus ribavirin and native IFN alfa-2b plus ribavirin eg 429 vs 323 p 04327 subsequent investigations reported SVR rates of 50 to 79 in patients receiving PEG-IFN alfa-2b plus ribavirin 800-1200 mgday for 48 weeks Overall meta-analysis of clinical trial data shows that SVR rates are significantly higher among genotype 4 patients receiving PEG-IFN alfa plus ribavirin than in those receiving IFN-alfa plus ribavirin 55 vs 30 p 0008833 This analysis also confirms the importance of adequate ribavirin dosing with higher SVR rates in patients receiving PEG-IFN alfa in combination with high-dose 1000-1200 mgday and low-dose 800 mgday ribavirin 720 and 458 respectively p value not presented The importance of ribavirin dosing in genotype 4 patients with chronic hepatitis C is also demonstrated in an analysis of the genotype 4 patients included in the registration studies for PEG-IFN alfa-2a22 34 In this analysis SVR rates were 79 among patients receiving PEG-IFN alfa-2a 180 mcgweek plus ribavirin 1000-1200 mgday for 48 weeks compared with 63 in those receiving the same regimen plus a lower dose of ribavirin 800 mgdayThe optimization of treatment duration is critical in ensuring that SVR rates are maximized without exposing the patient to an unnecessarily long treatment regimen that may have unfavorable implications in terms of cost and tolerability The question of optimal treatment duration for genotype 4 chronic hepatitis C was addressed in a prospective randomized study in which patients received PEG-IFN alfa-2b 15 mcgkgweek plus ribavirin 1000-1200 mgday for 24 36 or 48 weeksOverall SVR rates were significantly higher in patients receiving treatment for 36 or 48 weeks than in those treated for 24 weeks 66 and 69 vs 29 p 0001 for each comparison Fig 2 Relapse appeared to be a major factor in determining treatment outcomes virologic relapse during follow-up was highest among patients treated for 24 weeks 20 of 45 44 but relatively rare among the longer treatment arms
There was no significant difference between the 36-week and 48-week treatment regimens for the overall cohort However among patients with baseline viral load 2 million copiesmL who attained SVR 65 were treated for 48 weeks and 35 were treated for 36 weeks all patients with high baseline viral load treated for 24 weeks failed to attain SVR This suggests that the 48-week treatment regimen may be better suited to patients with high baseline viremia The efficacy and safety of pegylated interferon 2a has not be adequately evaluated in chronic hepatitis C genotype 4 patients in well conducted clinical trials involving well characterized cohorts and long follow up
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None