A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Combination With Copegus (Ribavirin) in Patients With Chronic Hepatitis C (CHC) Enrolled in a Methadone Maintenance Treatment Program.

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of PEGASYS plus ribavirin in previous intravenous (iv) drug users who have CHC and are currently enrolled in a methadone maintenance treatment program. The anticipated time on study treatment is 1-2 years, and the target sample size is <100 individuals.

Official Title
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An Open-Label, Multi-Center, Randomized, Safety, Feasibility and Tolerability Pilot Study of Pegasys® (Peginterferon Alfa-2a) Plus Copegus® (Ribavirin) in Previous Intravenous Drug Users Who Are Currently Enrolled in a Methadone Maintenance Treatment Program.

Conditions
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Hepatitis C, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients at least 18 years of age CHC infection, genotype 1, 2, or 3 naive to treatment for CHC infection enrolled in a methadone maintenance program with documented attendance for at least 3 months use of 2 forms of contraception during the study on both men and women Exclusion Criteria: previous treatment for CHC infection co-infection with human immunodeficiency virus (HIV) current use of IV or other illicit drugs decompensated cirrhosis women who are pregnant or breastfeeding

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Direct Observed Therapy<br>Participants will receive the peginterferon alfa-2a plus ribavirin at the clinic as: subcutaneous peginterferon alfa-2a 180 microgram (mcg) (once in a week) for 24 weeks for Genotype 2 or 3 (G2/3), and for 48 weeks for Genotype 1 (G1); oral ribavirin 800 milligram (mg)/day (twice in a day) for 24 weeks for G2/3, and 1000 or 1200 mg/day (twice in a day) for 48 weeks for G1. | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc weekly for 24 weeks (G 2/3) or 48 weeks (G 1)<br>Drug: ribavirin<br>* 1000/1200mg (< or >= 75 kg, respectively), po in two doses daily for 48 weeks (G 1) or 800 mg po in two doses daily for 24 weeks (G 2/3)<br>|
| Experimental: Self-Administration Therapy<br>Participants will receive the peginterferon alfa-2a plus ribavirin at home as: subcutaneous peginterferon alfa-2a 180 mcg (once in a week) for 24 weeks for G2/3, and for 48 weeks for G1; oral ribavirin 800 mg/day (twice in a day) for 24 weeks for G2/3, and 1000 or 1200 mg/day (twice in a day) for 48 weeks for G1. | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc weekly for 24 weeks (G 2/3) or 48 weeks (G 1)<br>Drug: ribavirin<br>* 1000/1200mg (< or >= 75 kg, respectively), po in two doses daily for 48 weeks (G 1) or 800 mg po in two doses daily for 24 weeks (G 2/3)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Completion Rate (TCR) | TCR is defined as the number of participants who completed the prescribed duration of the study treatment. TCR for G1 participants is defined as the number of participants who had a missing value or >= 2-log10 decrease in Hepatitis C virus-ribonucleic acid (HCV RNA) at Week 12 and completed 48 weeks of study treatment or had a < 2-log10 decrease from baseline at Week 12 and completed at least 12 weeks of study treatment. TCR for G2/ 3 participants is defined as the number of participants who completed 24 weeks of study treatment. | Up to 24 weeks for G2/3; up to 48 weeks for G1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Sustained Virological Response (SVR) Rate at 24 Weeks Post Treatment (Week 48 for G2/3 and Week 72 for G1) | SVR is defined as the number of participants with undetectable HCV-RNA (< 10 international unit per milliliter [IU/mL]) at 24 weeks post treatment completion. | Week 48 for G2/3 and Week 72 for G1 | 
| Number of Participants With Virological Response Rate at Weeks 12, 24, and 48 (G1 Only) During Treatment and at 12 Weeks After Treatment Completion | Virological Response Rate is defined as the number of participants with undetectable HCV-RNA (< 10 IU/mL). Treatment completion (end of treatment [EOT]) for G1 was Week 48 and for G2 or 3 was Week 24. | Weeks 12, 24, and 48 for G1 and Weeks 12 and 24 for G2/3; 12 and 24 weeks after EOT for G1 (Weeks 60 and 72) and G2/3 (Weeks 36 and 48) | 
| Number of Participants With Biochemical Response Rate at Weeks 12, 24, and 48 (G1 Only) During Treatment and at 12 and 24 Weeks After Treatment Completion | Biochemical response is defined as the number of participants with a normal serum alanine aminotransferase (ALT) concentration (i.e., ALT < 30 U/L). EOT for G1 was Week 48 and for G2/3 was Week 24. | Weeks 12, 24, and 48 for G1 and Weeks 12 and 24 for G2/3; 12 and 24 weeks after EOT for G1 (Weeks 60 and 72) and G2/3 (Weeks 36 and 48) | 
| Number of Participants With > =2 Log Drop From Baseline or Undetectable HCV-RNA (<10 IU/mL) at Week 12 |  | Week 12 | 
| Mean Absolute Score of Beck Depression Inventory, Second Edition (BDI-II) | BDI-II is 21-item self-report instrument to assess severity of symptoms of depression. There is a four-point scale for each item ranging from 0 to 3. Degrees of depression defined by the total BDI-II score as: minimal (0 to 13), mild (14 to 19), moderate (20 to 28), and severe depression (>= 29). Higher scores reflective of greater severity (worse outcome). | Baseline (Day -30 to -1), EOT visit (Week 24 for G2/3 and Week 48 for G1), and end of study (EOS) visit (Week 48 for G2/3 and Week 72 for G1). | 
| Mean Change From Baseline in BDI-II Score to EOT (Week 24/48) and EOS (Week 48/72) Visits | BDI-II is 21-item self-report instrument to assess severity of symptoms of depression. There is a four-point scale for each item ranging from 0 to 3. Degrees of depression defined by the total BDI-II score as: minimal (0 to 13), mild (14 to 19), moderate (20 to 28), and severe depression (>= 29). Higher scores reflective of greater severity (worse outcome). | Baseline (Day -30 to -1), EOT visit (Week 24 for G2/3 and Week 48 for G1), and end of study (EOS) visit (Week 48 for G2/3 and Week 72 for G1) | 
| Number of Participants With Degrees of Depression as Defined by the BDI-II Score | Participants with degrees of depression as defined by the BDI-II Score were reported. BDI-II is 21-item self-report instrument to assess severity of symptoms of depression. There is a four-point scale for each item ranging from 0 to 3. Degrees of depression defined by the total BDI-II score as: minimal (0 to 13), mild (14 to 19), moderate (20 to 28), and severe depression (>= 29). Higher scores reflective of greater severity (worse outcome). | Up to Week 72 | 
| Mean Absolute Scores for Hepatitis Quality-of-Life Questionnaire (HQLQ) at EOT (Week 24/48) Visit and 24 Weeks After EOT Visit | The HQLQ is a multiple-choice questionnaire includes the eight individual qualify-of-life scales of the Medical Outcomes Study 36-item Short-form Health Survey as: Social functioning (SF), role limitations due to emotional problems (RE), vitality (VT), general mental health (MH), physical functioning (PF), role limitations due to physical problems (RP), freedom from bodily pain (BP), and general health (GH). In addition, two other generic scales (positive well-being [PWB] and health distress [HD]) and two hepatitis-specific scales (limitations because of chronic hepatitis C [HLIM] and health distress because of chronic hepatitis C [HHD]) were included. Scores were scaled to a 0 to 100 range, with 0 = bad and 100 = good. A higher score indicates an improvement. | Baseline (Day -30 to -1), 24 weeks after EOT visit (Week 48 for G2/3 and Week 72 for G1) | 
| Number of Participants With Compliance to the Prescribed Treatment Regimen | Participants with compliance to the prescribed treatment regimen for peginterferon alfa-2a and ribavirin was reported. Compliance was calculated as (total cumulative dose taken) / (total cumulative original dose prescribed for the entire study) x 100. Total treatment duration = Maximum doses of peginterferon alfa-2a and ribavirin in days / (48*7) for G1, total treatment duration = Maximum doses of peginterferon alfa-2a and ribavirin in days / (24*7) for G2/3. | Up to Week 24 for G 2/3; up to Week 48 for G1 | 
| Number of Participants With Abnormal Vital Signs | Vital Signs included systolic blood pressures (SBP), diastolic blood pressures (DBP), and pulse rate (PR). Abnormal vital signs were reported as low or high abnormal. It was defined as < 85 mm Hg or > 180 mm Hg with a change from baseline of > 20%; DBP as > 110 mm Hg with a change from baseline of > 20%; and PR as < 50 bpm and > 120 bpm with a change from baseline of > 20%. | Up to 24 weeks of treatment-free follow-up visit (Week 48 for G2/3 and Week 72 for G1) | 
| Number of Participants With Marked Laboratory Abnormalities (Hematology) | Hematology included hematocrit (fraction), hemoglobin, platelets count, Red blood cells (RBC), White blood cell (WBC), eosinophils, lymphocytes, monocytes, neutrophils, Partial Thromboplastin time (PTT), Prothrombin Time International Normalized Ratio (PT INR). Laboratory values falling outside the marked reference range as defined by Roche's International Guideline for the Handling and Reporting of Laboratory Data, and were clinically relevant change from baseline were considered marked laboratory abnormalities. It was reported as low or high abnormal. | Up to 24 weeks post treatment (Week 48 for G2/3 and Week 72 for G1) | 
| Number of Participants With Marked Laboratory Abnormalities (Biochemistry) | Laboratory values falling outside the marked reference range as defined by Roche's International Guideline for the Handling and Reporting of Laboratory Data, and were clinically relevant change from baseline were considered marked laboratory abnormalities. It was reported as low or high abnormal. | Up to 24 weeks post treatment (Week 48 for G2/3 and Week 72 for G1) | 
| Number of Participants With Any Adverse Events (AEs), Any Serious Adverse Events (SAEs), and Study Discontinuation | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. Reason for discontinuation was categorized as safety and non-safety, where safety reasons included abnormality of laboratory tests, AEs, and death; and non-safety reasons included insufficient therapeutic response, early improvement, violation of selection criteria at entry, other protocol violation, refused treatment, failure to return and other. Participants who discontinued the study with any reason were recorded. | Up to 24 weeks post treatment (Week 48 for G2/3 and Week 72 for G1) |