A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Combination With COPEGUS (Ribavirin) in Interferon-Naive Patients With Chronic Hepatitis C Infection (CHC).

Study Overview
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Brief Summary
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The effects of treatment with different doses of PEGASYS in combination with different doses of ribavirin will be evaluated in patients with CHC genotype 1 who have a high viral titer, body weight greater than 85kg (187lbs) and no prior treatment with interferon. The anticipated time on study treatment is 3-12 months and the target sample size is 100-500 individuals.

Official Title
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Randomized, Multicenter, Double-blind, Phase IV Pilot Study Evaluating the Effect of PEGASYS Doses of 180 ug or 270 ug in Combination With Copegus Doses of 1200 mg or 1600 mg on Viral Kinetics, Virological Response, Pharmacokinetics, and Safety in Interferon-naïve Patients With Chronic Hepatitis C Genotype 1 Virus Infection of High Viral Titer and Body Weight Greater Than 85 kg

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: ribavirin [Copegus]
* Drug: ribavirin [Copegus]
* Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]
* Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >=18 years of age; body weight >85kg (187lbs); CHC (genotype 1); liver biopsy (in <24 calendar months of first dose), with results consistent with CHC infection; use of 2 forms of contraception during study and 6 months after the study in both men and women. Exclusion Criteria: women who are pregnant or breastfeeding; male partners of women who are pregnant; conditions associated with decompensated liver disease; other forms of liver disease, including liver cancer; human immunodeficiency virus infection; previous treatment with an interferon, ribavirin, viramidine, levovirin or amantadine.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PEG-IFN Alfa-2a 180 μg +Ribavirin 1200 mg<br>Participants received 180 μg of PEG-IFN [peginterferon] alfa-2a in 1 mL solution administered [subcutaneously] sc, once weekly + 1200 mg of ribavirin (200 mg/tablet) + ribavirin placebo (2 tablets) administered [orally ] po daily in split doses for 48 weeks | Drug: ribavirin [Copegus]<br>* 600mg po bid for 48 weeks<br>Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]<br>* 180 micrograms sc weekly for 48 weeks<br>|
| Experimental: PEG-IFN Alfa-2a 180 μg + Ribavirin 1600 mg<br>Participants received 180 μg of PEG-IFN [peginterferon] alfa-2a in 1 mL solution administered [subcutaneously] sc, once weekly + 1200 mg of ribavirin (200 mg/tablet) + ribavirin placebo (2 tablets) administered [orally ] po daily in split doses for 48 weeks | Drug: ribavirin [Copegus]<br>* 800mg po bid for 48 weeks<br>Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]<br>* 180 micrograms sc weekly for 48 weeks<br>|
| Experimental: PEG-IFN Alfa-2a 270 μg + Ribavirin 1200 mg<br>Participants received 270 μg of PEG-IFN alfa-2a in 1-mL solution administered sc once weekly + 1200 mg of ribavirin (200 mg/tablet) + ribavirin placebo (2 tablets) administered po daily in split doses for 48 weeks | Drug: ribavirin [Copegus]<br>* 600mg po bid for 48 weeks<br>Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]<br>* 270 micrograms sc weekly for 48 weeks<br>|
| Experimental: PEG-IFN Alfa-2a 270 μg + Ribavirin 1600 mg<br>Participants received 270 μg of PEG-IFN alfa-2a in 1-mL solution administered sc once weekly + 1600 mg of ribavirin (200 mg/tablet) administered po daily in split doses for 48 weeks. | Drug: ribavirin [Copegus]<br>* 800mg po bid for 48 weeks<br>Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]<br>* 270 micrograms sc weekly for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA Profile During The First 24 Weeks | Viral loads (quantitative HCV RNA) collected during the initial 24 weeks were first logarithmically (based 10) transformed. Results falling below the assay sensitivity level were set to the assay sensitivity level before the analyses. Thus, a qualitative HCV RNA negative result was set to 50 IU/mL (or 100 copies/mL). A qualitative HCV RNA positive result along with an unquantifiable HCV RNA result from the quantitative assay corresponded to a numeric HCV RNA result of 600 IU/mL (or 1000 copies/mL). | Baseline (Day 1), At 72 hour (h), Week (W)-1, 2, 4, 12, 24 | 
| Percentage of Participants With Virological Response Over Time to Week 24 | Virological response over time to Week 24 is defined as the percentage of participants with undetectable HCV RNA as measured by the Roche Amplicor HCV Test, V. 2.0 (detection limit = 50 IU/mL) at 72 hours and at weeks 1, 2, 12, and 24. | 72 hours post-dose, Weeks 1, 2, 4, 12, and 24 | 
| Percentage of Participants With Predicted Sustained Virological Response | The predicted sustained virological response (SVR) for each treatment group, is determined using a model based on the log10-transformed HCV viral load in copies/mL at Week 4 and the virological response status at Week 12. Each participant was classified as a predicted SVR if p was ≥ 0.5 or as a non-SVR if p was <0.5. The percentage was calculated from the number of participant (N) analyzed under Distribution of the predicted probability of an SVR. | Week 4 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virological Response | SVR is defined as the percentage of participants with undetectable HCV RNA as measured by the Roche Amplicor HCV Test, v 2.0 (detection limit = 50 IU/ml) at the end of the 24-week untreated follow-up period. | Week 72 | 
| Percentage of Participants With Virological Response at the End of the Treatment Period | Virological response at the end of the treatment period is defined as the percentage of participants with undetectable HCV RNA as measured by the Roche Amplicor HCV Test, v 2.0 (detection limit = 50 IU/mL) at the completion of the treatment period. | Week 48 | 
| Percentage of Participants With Virological Response At 12 Weeks After The End of The Treatment Period | Virological response at 12 weeks after the end of the treatment period is defined as the percentage of participants with undetectable HCV RNA as measured by the Roche Amplicor HCV Test, v 2.0 (detection limit = 50 IU/mL) at 12 weeks after completion of the treatment period. | Week 60 | 
| Percentage of Participants With Adverse Events and Serious Adverse Events | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. A serious adverse event is any adverse event (SAE) that can result in death or is Life-threatening or required in-patient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect; or is medically significant or requires intervention to prevent one or other of the outcomes listed above. | Up to Week 72 | 
| Percentage of Participants With Marked Laboratory Abnormalities | Marked laboratory abnormalities are the values outside the roche defined reference range.It is hemoglobin 11.0 - 20.0 (g/dL),platelets 100 - 700 (10^9/L), lymphocyte 1.00 - 6.30 (10^9/L),neutrophils 1.50 or more (10^9/L), white blood cells(WBC) 3.0 - 18.0 (10^9/L),serum glutamic-pyruvic transaminase (SGPT) 0 - 60 (U/L), serum glutamic oxaloacetic transaminase (SGOT) 0 - 50 (U/L), alkaline phosphatase 0 - 190 (U/L),albumin was 27.0 or more (g/L),gamma glutamyl transferases (GGT) 0 - 120 (U/L),Total protein 55 - 87 (g/L),total bilirubin 0 - 34.2 (μmol/L),BUN 0 - 14.3 (mmol/L),creatinine 0 - 154 (μmol/L),chloride 95 - 115 (mmol/L),potassium 3.0 - 6.0 (mmol/L), sodium 130 - 150 (mmol/L),thyroid stimulating hormone (TSH) 0.0 - 10.0 (mU/L),triglycerides 0.00 - 2.83 (mmol/L), calcium 2.00 - 2.90 (mmol/L),phosphate 0.75 - 1.60 (mmol/L),Blood Glucose 2.80 - 11.10 (mmol/L),Uric Acid 0 - 600 (μmol/L),proteinuria 0 - 1 (0 to 4+), glycosuria 0 - 1 (0 to 4+), hematuria 0 - 1 (0 to 4+). | Up to Week 60 | 
| Percentage of Participants With Abnormal Vital Signs | Vital signs (Systolic blood pressure, Diastolic blood pressure, Pulse rate) were considered to be abnormal and of potential clinical relevance if the values measured for these parameters represented a change from baseline of greater than 20% in the direction of worsening. High diastolic blood pressure is defined as >110 mmhg and >20% increase from baseline. High systolic blood pressure is defined as >180 mmhg and >20% increase from baseline. Low systolic blood pressure is defined as <85 mmhg and >20% decrease from baseline. High heart rate is defined as >120 beats/minute and >20% increase from baseline. Low heart rate is defined as < 50 beats/minute and >20% decrease from baseline. | Up to Week 72 | 
| Total BDI-II (Beck Depression Inventory) Scores | The BDI-II is a self-reported assessment of 21 items which included sadness, pessimism, past failure, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, changes in sleeping pattern, irritability, changes in appetite, concentration difficulty, tiredness or fatigue, loss of interest in sex that are summarized by treatment group. All except two items had four statements that were scored on a scale ranging from 0 to 3. The maximum total score was 63. The scores for each item were summed to obtain the total for that assessment. The participants neurological status could then be categorized as follows: minimal depression: 0 to 13; mild depression: 14 to 19; moderate depression: 20 to 28; and severe depression: 29 to 63. The BDI-II questionnaire was self-administered by the patient at each visit. | From Baseline (Day 1) to Week 72 |