Clinical Trial Result Information
Protocol number
ML17131
Title of Study
Interim analysis of group D in genotype 1 / 4 study: Randomized, multicenter study to find optimal treatment duration in patients with chronic hepatitis C and subtype 1 or 4 depending on HCV RNA level at week 12.
Sponsor
Roche Austria GmbH
Company division
Pharmaceutical
Product name
PEGASYS
Generic name
peginterferon alfa-2a (40KD)
Therapeutic area
Hepatitis C, Chronic
Clinical study summary
This was a randomized, multicenter, efficacy and safety study to compare the effect of two treatment periods with PEGASYS (peginterferon alfa-2a (40KD)) plus ribavirin on sustained virological response in patients with chronic hepatitis C, genotype 1 or 4. This summary contains results of an interim analysis conducted in a sub-group of patients who had a rapid virological response at week 4.
Study center(s)
26 patients in Austria; 13 centers contributed patients to interim analysis
Phase of development
IV
Objectives
To assess virological responses at the end of treatment and at the end of follow-up in a subgroup of patients with a rapid virological response, defined as undetectable HCV RNA at week 4, to evaluate whether reducing treatment duration with PEGASYS plus ribavirin to 24 weeks adversely impacts achievement of a sustained virological response.
Methodology
This report provides an interim analysis of an ongoing trial in patients infected with HCV genotype 1 or 4. This interim analysis evaluated data from all rapid virological responder patients enrolled in study ML17131 (ie. those who had undetectable HCV RNA at week 4). Patients received a fixed dose of 180µg of PEGASYS weekly and 1000/1200mg/day of ribavirin for the first 12 weeks. A patient's disease status was assessed by measuring HCV RNA levels with quantitative and qualitative assays at screening, and virological response was assessed at week 4. An additional quantitative assay was performed at week 12. Patients with undetectable HCV RNA (<50 IU/mL, or <100 copies/mL) at week 4 were assigned to 24 weeks of total treatment duration. During the treatment period, patients in this group returned for evaluations at weeks 2 and 4 and then monthly until the end of week 24. After completing treatment, patients were seen after 4, 12 and 24 weeks.
Number of patients (planned/analyzed)
108 in subgroup in interim analysis.
Diagnosis and main criteria for inclusion
Men and women, previously untreated with any pegylated interferon, between 18 and 65 years old with serologically proven chronic hepatitis C (CHC) and HCV genotype 1 or 4.
Test product, dose and mode of administration or test procedure
PEGASYS (peginterferon alfa-2a (40KD)) 180μg, subcutaneous, once weekly.
Ribavirin: 1000 or 1200mg according to body weight, oral, daily.
Duration of treatment
24 weeks
Reference therapy, dose and mode of administration or reference procedure
N/A
Criteria for evaluation (efficacy, safety)
Efficacy: Sustained viral response (undetectable HCV RNA at 24 weeks after completion of the 24-week treatment period) in rapid virological responders.
Safety: Adverse events and laboratory parameters.
Statistical methods
No inferential statistical analysis was performed on the data. Asymptotic binomial two-sided 95% confidence intervals were provided for sustained virological response and maintenance of response.
Summary (efficacy, safety, other results)
αA total of 108 patients were included in the interim analysis safety population; the rapid virological response (RVR) population consisted of 101 patients. Of these, 77 were genotype 1 patients and 24 were genotype 4 patients. The majority (83%) of patients in the RVR had a low baseline viral load (≤800,000 IU/mL).
Efficacy: An overall sustained virological response of 80% was achieved in genotype 1 and 4 patients who had a rapid virological response at week 4. A sustained virological response of 77% (59/77) was achieved in genotype 1 patients in the rapid virological response population. The proportion of genotype 1 patients in the rapid virological response population with a high baseline viral load (≥800,000 IU/mL) who achieved a sustained virological response (58%; 7/12) was lower than the proportion with a low baseline viral load (≤800,000 IU/mL) who achieved a sustained virological response (80%; 52/65). Genotype 4 patients in the rapid virological response population achieved an overall sustained virological response of 92% (22/24). There was little difference in the proportion of patients who achieved sustained virological response between those with a low viral load (89%; 16/18) and those with a high viral load (100%; 6/6). Sustained virological response was comparable in cirrhotic (79%) and noncirrhotic (80%) genotype 1 and 4 patients with a rapid virological response. The majority of genotype 1 patients (83%; 59/71) and all genotype 4 patients (100%; 22/22) who had a virological response at the end of treatment maintained their end-of-treatment response at the end of follow-up.
Safety: The safety profile of PEGASYS and ribavirin combination therapy observed in the patients from the rapid virological response population in this interim analysis was similar to that observed in previous studies of 24 weeks of treatment with PEGASYS and ribavirin combination therapy. The majority of patients were able to tolerate 24 weeks of therapy, with 94% of patients completing at least 21 weeks of treatment. Only one patient discontinued study treatment for an adverse event, thrombophlebitis, which was considered by the investigator to be unrelated to study medication and resolved after treatment was discontinued. Only 7% of patients experienced severe or serious adverse events, and no life-threatening AEs or deaths occurred. A total of 29% of patients required dose modification of study drugs for an AE. Consistant with previous results, decreases in neutrophil counts were the most significant laboratory abnormality, with 7% of patients experiencing grade 4 neutropenia (<0.5 x 109/L).
Conclusions
A sustained virological response was achieved by a very high proportion of genotype 1 and 4 infected patients with a low viral load at baseline (≤800,000 IU/mL) who became HCV RNA negative at week 4 of treatment and remained HCV RNA negative at week 24 when treated with the combination of 180µg of PEGASYS once weekly plus ribavirin 1000/1200 mg/day for 24 weeks. Close to 90% of genotype 1 and 4 patients with a low viral load and a rapid virological response maintained their end-of-treatment response. The safety profile of PEGASYS plus ribavirin combination therapy was consistent with that observed in previous studies with 24-weeks of combination therapy. PEGASYS plus ribavirin combination therapy was generally well tolerated, with no patients discontinuing treatment for safety reasons assessed to be related to study medication.
Treating genotype 1 and 4 patients who have a low baseline viral load and rapid virological response for 24 weeks significantly reduces the treatment burden for patients and is expected to provide better overall tolerability and safety compared with treatment for 48 weeks.
Publications (references, if available)
Ferenci et al. J Hepatol 2006;44(suppl 2):S6 (Abstract 8).
Date of report
5/29/2007
Click here for the protocol registry listing of this trial.
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