Latino Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) and COPEGUS (Ribavirin) in Treatment-Naive Patients With Chronic Hepatitis C-Genotype 1.

Study Overview
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Brief Summary
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This single arm study will evaluate the efficacy and safety of PEGASYS (180 micrograms sc weekly) plus ribavirin (1000-1200mg po daily) in treatment-naive Latino patients versus non-Latino Caucasian patients with chronic hepatitis C- genotype 1. The anticipated time on study treatment is 3-12 months and the target sample size is 500+ patients.

Official Title
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A Prospective, Multicenter, Open-label, Comparative, Efficacy Study of Pegasys® Plus Copegus® in Treatment-naïve Latino Patients With Chronic Hepatitis C-genotype 1, as Compared to Treatment-naïve Non- Latino Caucasian Patients With Chronic Hepatitis C-genotype 1

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Ribavirin
* Drug: Peginterferon alfa-2a
* Drug: Ribavirin
* Drug: Peginterferon alfa-2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients 18-65 years of age chronic hepatitis C , genotype 1 serologic evidence of CHC infection by an antibody test chronic liver disease, consistent with CHC infection on a liver biopsy obtained within the past 18 months compensated liver disease use of 2 forms of contraception during the study in both men and women Exclusion Criteria: previous interferon or ribavirin therapy systemic antiviral therapy less than 24 weeks before first dose of study drug or expected need for this treatment any time during the study medical condition associated with chronic liver disease (eg, hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure) decompensated liver disease women who are pregnant or breastfeeding

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Latino<br>Participants received peginterferon alfa-2a 180 microgram (mcg)/0.5 mL by subcutaneous injection once a week in combination with ribavirin 1000 or 1200 mg per day, which was taken orally in split doses for 48 weeks. Participants with <75 kg (165 lbs) of body weight received 1000 mg/day (400 mg in the morning and 600 mg in the evening). Participants with >=75 kg (165 lbs) of body weight received 1200 mg/day (600 mg in the morning and 600 mg in the evening). | Drug: Ribavirin<br>* 1000-1200mg po daily for 48 weeks<br>Drug: Peginterferon alfa-2a<br>* 180 micrograms sc/week for 48 weeks<br>|
| Experimental: Non-Latino White<br>Participants received peginterferon alfa-2a 180 mcg/0.5 mL by subcutaneous injection once a week in combination with ribavirin 1000 or 1200 mg per day which was taken orally in split doses. Participants with <75 kg (165 lbs) of body weight received 1000 mg/day. Participants with >=75 kg (165 lbs) of body weight received 1200 mg/day for 48 weeks. | Drug: Ribavirin<br>* 1000-1200mg po daily for 48 weeks<br>Drug: Peginterferon alfa-2a<br>* 180 micrograms sc/week for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response at Week 72 | Sustained Virologic Response (SVR) is defined as percentage of participants with an undetectable hepatitis C virus-RNA (HCV-RNA) measurement (<28 International Unit (IU)/millilitre (mL)) assessed 24 weeks post-treatment (week 72) which was assessed by Roche High Pure System/COBAS TaqMan HCV Test. | At Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Virologic Response | Percentage of participants achieving a virologic response defined as an undetectable HCV-RNA measurement (HCV-RNA <28 IU/mL by Roche High Pure System/COBAS TaqMan HCV Test) | At Weeks 4, 12, 24, 48, 60, and 72 | 
| Percentage of Participants With Early Virologic Response at Week 4 | Percentage of participants with an early virologic response defined as an HCVRNA >=1 log10 drop from baseline or undetectable HCV-RNA measurement at Week 4 (lower limit of detection 28 IU/mL). | At Week 4 | 
| Percentage of Participants With Early Virologic Response at Week 12 | Percentage of participants with an early virologic response defined as an HCV-RNA >=2 log10 drop from baseline or undetectable HCV-RNA measurement at Week 12 (lower limit of detection 28 IU/mL). | At Week 12 | 
| Change From Baseline in HCV-RNA Log10 Titers Over the Period Of Time | The table below shows HCV-RNA log10 titers change from baseline values by study week and by study group. Analysis was performed for participants with a baseline and at least 1 post-baseline HCV-RNA assessment. HCV-RNA quantitation was performed using Roche High Pure System/COBAS® TaqMan® HCV Monitor Test. HCV-RNA measurement lower limit of detection was 28 IU/mL. | From Baseline (Week 0) to Weeks 4, 12, 24, 48, 60 and 72 | 
| Percentage of Participants With Biochemical Response | Biochemical response was defined as normal serum alanine transaminase (ALT) measurement. For ALT measurement the normal range is 5-37 IU/L. | At Weeks 4, 12, 24, 48, 60 and 72 | 
| Percentage of Participants With ISHAK Histological Activity Index Response | ISHAK Histological Activity Index (HAI) activity response is defined as a decrease from baseline of at least 2 points (≥2 points drop from baseline) in the ISHAK modified HAI (necroinflammatory) score at week 72. ISHAK modified HAI activity (necroinflammatory) score is a total score of periportal ± bridging (P/B) necrosis + confluent necrosis + focal necrosis + portal inflammation (maximum score for each participant = 18). Where P/B necrosis grading as 0 = absent; 1 = mild; 2 = mild/moderate; 3 = moderate; 4 = severe; Confluent necrosis grading as 0 = absent; 1 = focal; 2 = zone 3 some areas; 3 = zone 3 most areas; 4 = zone 3 occasional portal; 5 = zone 3 multiple; 6 = panacinar necrosis and Focal necrosis grading as 0: absent; 1: < = 1 focus; 2: 2 to 4 foci; 3: 5 to 10 foci; 4: > 10 foci; Portal Inflammation grading: 0 = none; 1 = mild; 2 = moderate; 3 = moderate/marked; 4 = marked/all portal. | At Week 72 | 
| Mean Change From Baseline in ISHAK HAI Activity (Necroinflammatory) at Week 72 | ISHAK modified HAI activity (necroinflammatory) score is a total score of P/B necrosis + confluent necrosis + focal necrosis + portal inflammation (maximum score for each Participant = 18). Where P/B necrosis grading as 0 = absent; 1 = mild; 2 = mild/moderate; 3 = moderate; 4 = severe; Confluent necrosis as 0 = absent; 1 = focal; 2 = zone 3 some areas; 3 = zone 3 most areas; 4 = zone 3 occasional portal; 5= zone 3 multiple; 6= panacinar necrosis and Focal necrosis as 0: absent; 1: <= 1 focus; 2: 2 to 4 foci; 3: 5 to 10 foci; 4: > 10 foci; Portal Inflammation: 0 = none; 1 = mild; 2 = moderate; 3 = moderate/marked; 4 = marked/all portal. The difference between study groups in change from baseline in ISHAK modified HAI activity score at week 72 was tested using an analysis of covariance (ANCOVA) model with ethnicity and baseline ISHAK HAI score as the fixed effects. | From Baseline (Week 0) to Week 72 | 
| Mean Change From Baseline in Fibrosis Score Based on ISHAK at Week 72 | ISHAK Histological Activity Index (HAI) activity response is defined as a decrease from baseline of at least 2 points (≥2 points drop from baseline) score at week 72. Baseline prognostic factors in the original model include ethnicity, sex, age, baseline ALT quotient, baseline HCV-RNA level, and ISHAK fibrosis and activity scores at baseline. ISHAK modified HAI fibrosis scale by fibrosis grading category as F0= no fibrosis; F1= some portal areas; F2= most portal areas; F3= bridging fibrosis; F4= bridging and portal to central; F5 = marked bridging; F6 = Cirrhosis; where '0' being the best and '6' being the worst. Decrease in score from baseline indicates improvement. The difference between study groups in change from baseline in ISHAK modified HAI activity score at week 72 was analysed. | From Baseline (Week 0) to Week 72 | 
| Percentage of Participants With Improved, Stable and Worsened ISHAK Fibrosis Score | Overall ISHAK Fibrosis Score is defined as Improved: >= 1 category decrease in fibrosis scale; Stable: no change in fibrosis scale; Worsened: >1 category increase in fibrosis scale. | At Week 72 | 
| Mean Change From Baseline in Activity and Fibrosis Scores Based on METAVIR Activity at Week 72 | METAVIR activity scores are categorised as histological activity (A) 0 = none; A1 = mild; A2 = moderate; A3 = severe where '0' being 'No activity' and '3' being 'the sever activity'. Changes in liver inflammation defined as Improved: Participants whose METAVIR activity score at up to Month-72 decreases by 1 or more units compared to baseline; stable: Participants whose METAVIR activity score at up to Month-72 is the same as the baseline score; worsened: Participants whose METAVIR activity score at up to Month-72 increases by 1 or more units compared to baseline. METAVIR fibrosis scores are categorised as fibrosis (F) 0 = no fibrosis; F1 = without septa; F 2 = with septa; F3 = many septa; F4 = cirrhosis where; '0' being the best and '4' being the worst. Decrease in score from baseline indicates improvement. The difference between study groups in change from baseline in activity and fibrosis scores based on METAVIR at week 72 was analysed. | From Baseline (Week 0) to Week 72 | 
| Percentage of Participants With Improved, Stable, and Worsened METAVIR Activity Score | METAVIR activity scale included activity defines as, Improved: >= 1 category decrease in activity score; stable: no change in activity score; worsened: > = 1 category increase in activity score. | At Week 72 | 
| Percentage of Participants With Improved, Stable, and Worsened METAVIR Fibrosis Score | METAVIR fibrosis score is categorized as, Improved: >= 1 category decrease in activity score; stable: no change in activity score; worsened: >= 1 category increase in activity score. | At Week 72 | 
| Mean Change From Baseline in Fat Score at Week 72 | Grading categories for the fat scale were as follows: 1 = <5% hepatocytes; 2 = 6 - 33% hepatocytes; 3 = 34 - 66% hepatocytes; 4 = 67 - 100% hepatocytes. | From Baseline (Week 0) to Week 72 | 
| Percentage of Participants With Improved, Stable and Worsened Fat Score From Baseline to Week 72 | Fat scores are categorised as Improved: > 1 category decrease in fat scale; stable: no change in fat scale; worsened: >= 1 category increase in fat scale. | From Baseline (Week 0) to Week 72 | 
| Percentage of Participants With Non-zero Nonalcoholic Steatohepatitis Score | The Nonalcoholic Steatohepatitis (NASH) included an assessment of sinusoidal fibrosis, Mallory bodies, and hepatocyte ballooning (HB). Grading categories for the NASH scales were as: Sinusoidal fibrosis: 0 = absent; 1 = involvement of some lobules; 2 = involvement of most lobules, without diffuse interstitial sinusoidal collagen deposition; 3 = Involvement of most or all lobules;, with diffuse interstitial fibrosis involving some or most of the lobules Mallory bodies: 0 = absent; 1 = involvement of some lobules; 2 = involvement of most lobules; 3= involvement of most or all lobules; and Hepatocyte ballooning: 0 = absent; 1 = involvement of some lobules; 2 = involvement of most lobules; 3= involvement of most or all lobules. | At Week 72 | 
| Mean Change in Fatigue Severity Scale Score and Fatigue Severity Scale Score Item 10 Visual Analog Scale Score From Baseline at Week 48 and Week 72 | The Fatigue Severity Scale (FSS) is a 10-item self-report questionnaire designed to assess tiredness, lack of energy, or total body give-out. Participants were to react to nine statements regarding fatigue over the previous 2 weeks, each on a scale (1 = completely agree, 7 = completely disagree). The FSS is the average of the scores on the 9 questions; ranging from 1-7, with lower scores indicating less fatigue. In addition, participants were to react to how much fatigue they had in the past 2 weeks by marking on a visual analogue scale (VAS) labelled at one end with no fatigue ('0' being the best) and at the other end with greater fatigue ('100' being the worst). Longer distance on the scale from no fatigue indicated greater fatigue. FSS values are presented based on questionnaire and visual analog scale. FSS values at week 48 and 72 are presented based on questionnaire and visual analog scale. | Baseline (Week 0), Week 48 and Week 72 | 
| Mean Change in 36-item Short Form Health Survey Total and Domain Scores From Baseline at Week 48 and 72 | The 36-item Short Form Health Survey (SF-36) is a 36-item self-report questionnaire that includes 8 domain scales The 8 domains are incorporated into 2 components: mental and physical. The mental component (MC) includes social functioning, role limitations-emotional, mental health, and vitality. The physical component (PC) includes physical functioning, role limitations-physical, bodily pain, and general health perception. Raw domain scores are transformed to a 0 to 100 scale, [0=worst score (or quality of life) and 100=best score]. Two summary scale scores were computed based on weighted combinations of the 8 domain scores (Physical and the Mental Component) where no minimum or maximum score; higher score indicate better health status. The difference between study groups in change from baseline in SF-36 score at week 48 and 72 was analysed. | Baseline (Week 0), Week 48 and Week 72 | 
| Number of Participants With Any Adverse Events and Serious Adverse Events | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An adverse event could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions that worsened during the study were reported as adverse events. A serious adverse event (SAE) was any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect. | Up to Week 72 | 
| Number of Participants With Marked Abnormal Laboratory Parameters | The below table includes participants with marked abnormal lab parameters. Standard reference ranges include: Hematocrit: (fraction) 0.37 - 0.49, Hemoglobin 130 - 180 g/L, Platelets 150 - 350 10^9/L, White Blood Cell (WBC) 4.5 - 11.0 10^9/L, Lymphocytes 1.00 - 4.80 10^9/L, Neutrophils 1.80 - 7.70 10^9/L, Aspartate aminotransferase (AST) 0-40 U/L, ALT 0 - 55 U/L, Total bilirubin 0 - 17 μmol/L, Thyroxine T4 58 - 140 nmol/L, Thyroid Stimulating Hormone (TSH) 0.0 - 5.0 million units (mU)/L, Albumin 35.0 - 55.0 g/L, Chloride 100 - 108 mmol/L, Calcium 2.10 - 2.60 mmol/L, Phosphate 0.84 - 1.45 mmol/L, Uric acid 214 - 506 μmol/L. | Up to Week 72 | 
| Number of Participants With Premature Withdrawals Due to Adverse Events or Laboratory Abnormalities | The table below includes participants with premature withdrawals due to adverse events or laboratory abnormalities. | Up to Week 72 |