A Study of PEGASYS (Peginterferon Alfa-2a) Plus Ribavirin in Patients With Chronic Hepatitis C (CHC), Genotype 2 or 3

Study Overview
=================
Brief Summary
-----------------
This randomized, parallel arm study will evaluate the efficacy and safety of Pegasys (peginterferon alfa-2a) in combination with 2 different doses of ribavirin in patients with chronic hepatitis C, genotype 2 or 3. Patients will be randomized to 4 treatment groups receiving Pegasys (180 mcg subcutaneously weekly) for either 16 or 24 weeks with one of two doses of ribavirin (400 mg or 800 mg orally daily). The anticipated time on study treatment is 16 or 24 weeks with a 24-week follow-up.

Official Title
-----------------
Randomized, Multicenter Study to Compare the Efficacy of Pegylated Interferon Alfa (PEG-IFN) in Combination With Two Different Doses of Ribavirin in Patients With Chronic Hepatitis C and Subtype 2/3

Conditions
-----------------
Hepatitis C, Chronic

Intervention / Treatment
-----------------
* Drug: peginterferon alfa-2a [Pegasys]
* Drug: peginterferon alfa-2a [Pegasys]
* Drug: ribavirin
* Drug: ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients, 18-65 years of age Chronic hepatitis C, genotype 2 or 3 Positive HCV RNA level in serum at screening (COBAS AMPLICOR MONITOR HCV test) Abdominal sonography within 3 months prior to study start Exclusion Criteria: Previous interferon and/or pegylated interferon and ribavirin therapy Liver cirrhosis, class B or C (Child-Pugh) Systemic anti-neoplastic or immunomodulatory treatment <=6 months before study drug History or evidence of medical condition associated with chronic liver disease other than chronic hepatitis C Decompensated liver disease Positive for HIV

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peginterferon/Ribavirin 800 mg (24 Weeks)<br>Participants received peginterferon alfa-2a (PEG-IFNα-2a) 180 mcg once weekly + Ribavirin 800 mg daily for 24 weeks (W). | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 24 weeks<br>Drug: ribavirin<br>* 800 mg orally daily<br>|
| Experimental: Peginterferon/Ribavirin 400 mg (24 Weeks)<br>Participants received PEG-IFNα-2a 180 mcg once weekly + Ribavirin 400 mg daily for 24 W. | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 24 weeks<br>Drug: ribavirin<br>* 400 mg orally daily<br>|
| Experimental: Peginterferon/Ribavirin 800 mg (16 Weeks)<br>Participants received PEG-IFNα-2a 180 mcg once weekly + Ribavirin 800 mg daily for 16 W. | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 16 weeks<br>Drug: ribavirin<br>* 800 mg orally daily<br>|
| Experimental: Peginterferon/Ribavirin 400 mg (16 Weeks)<br>Participants received PEG-IFNα-2a 180 mcg once weekly + Ribavirin 400 mg daily for 16 W. | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 16 weeks<br>Drug: ribavirin<br>* 400 mg orally daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Sustained Virologic Response Rate At 24 Weeks Post Completion of the Treatment | Sustained virological response was defined as the percentage of participants in each group with undetectable Hepatitis C virus-Ribonucleic acid (HCV-RNA) measurement at 24 weeks post completion of the treatment. | Up to Week 48 (24 weeks post completion of the treatment) | 
| Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 | Serum Hepatitis C Virus-RNA (HCV-RNA) was done by Polymerase chain reaction (PCR). Samples for a qualitative PCR (AMPLICOR® HCV Test v2.0) were obtained at Week 24 and Week 48. 'G2' and 'G3' indicates Genotype 2 and Genotype 3 respectively. | At Week 24 and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Virological Response at the End of the Treatment | Virological response at the end of the treatment (ETR) was defined as the percentage of participants with negative qualitative PCR in each group at completion of the treatment. ETR is defined as Week 16 and Week 24. | At Week 16 and Week 24 | 
| Percentage of Participants With Virologic Response Rates as Per Genotype at End of Treatment | Virologic Response was defined as undetectable HCV-RNA levels (determined by AMPLICOR HCV test) at Week 16 and Week 24. Virologic response rates based on genotype (G2 and G3) were reported. ETR is defined as Week 16 and Week 24. | At Week 16 and Week 24 | 
| Number of Participants With Any Adverse Events and Any Serious Adverse Events | An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. | Up to Week 48 | 
| Median Hemoglobin Levels at End of Treatment | Hemoglobin (Hb) levels at end of treatment (Week 16 and Week 24) were reported. The mean lowest Hb value after treatment starts with a median of 129 gram (g)/Litre (L). The far most frequent hemoglobin class was >=100 g/L. The purpose of assessing the Hb levels is associated with ribavirin dose. The primary toxicity of ribavirin dose (1000-1200 mg/day, maximum tolerated dose) is anemia with a reduction in hemoglobin levels generally occurring within the first 1-2 weeks of initiating therapy. Decreases in hemoglobin seen in the combination treatment of ribavirin and Interferon-alfa are managed with reduction in ribavirin dosage to 600 mg/day. | At Week 16 and Week 24 | 
| Mean SF-36 Scores at Baseline and Weeks 16, 24 and 48 | Short-Form Health Survey (SF-36) is a 36-item questionnaire measuring eight domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Where Baseline (BS) is Week 0. | At Baseline (Week 0) and Weeks 16, 24 and 48 | 
| Mean FSS Scores at Baseline and Weeks 16, 24 and 48 | The Fatigue Severity Scale (FSS) is a self-administered instrument that includes 9 items rated on a 7-point scale, measuring fatigue severity. The participants were asked to score each statement, based on how the statement applied to them over the preceding week. The fatigue severity score is the average of the scores on the 9 questions; scores range from 1-7, with lower scores indicating less fatigue. Baseline is defined as Week 0. | At Baseline (Week 0) and Weeks 16, 24 and 48 | 
| Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 | Psychiatric assessment were performed using Beschwerdeliste (BL) questionnaires. BL results were analyzed descriptively by visit, treatment group, genotype and opioid maintenance therapy status. The BL questionnaire items were scored by calculating the average response to all answered items. Items were graded 1=stark (affliction is strong) to 4=gar nicht (not present). The higher the BL score, the less afflictions were present for a participant. Baseline is defined as Week 0. | At Baseline (Week 0) and Weeks 16, 24 and 48 | 
| Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 | For the psychiatric assessment, the results of the Beck Depression Inventory (BDI) questionnaires were evaluated. BDI results were analyzed descriptively by visit, treatment group, genotype and opioid maintenance therapy status. BDI is 21 item participant rated inventory evaluates depression symptoms, cognition, and physical symptoms of fatigue, weight loss, lack of interest in sex. Individual items are scored on a 4 point scale (0 to 3), with 0=none/absent and 3=most severe. Total score: 0 to 63; higher score indicates more depression. Mean scores are presented by visit. Baseline is defined as Week 0. | At Baseline (Week 0) and Weeks 4, 8, 12, 24 and 48 | 
| Time to Viral Response | Time to viral response was calculated as Date of first negative PCR result after screening - date of PCR screening sample + 1 [in days]. Mean of number of days to viral response for overall population were reported. | Up to Week 48 |