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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.

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
peginterferon alfa-2a [Pegasys]
ribavirin
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Direct Observed Therapy

Self-Administration Therapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
Number of Participants With > =2 Log Drop From Baseline or Undetectable HCV-RNA (<10 IU/mL) at 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).
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).
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).
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.
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.
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%.
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.
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.
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.

Full Information

First Posted
July 12, 2004
Last Updated
February 4, 2016
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00087594
Brief Title
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.
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
November 2003 (undefined)
Primary Completion Date
October 2006 (Actual)
Study Completion Date
October 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Direct Observed Therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Self-Administration Therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
peginterferon alfa-2a [Pegasys]
Intervention Description
180 micrograms sc weekly for 24 weeks (G 2/3) or 48 weeks (G 1)
Intervention Type
Drug
Intervention Name(s)
ribavirin
Intervention Description
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)
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Completion Rate (TCR)
Description
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.
Time Frame
Up to 24 weeks for G2/3; up to 48 weeks for G1
Secondary Outcome Measure Information:
Title
Number of Participants With Sustained Virological Response (SVR) Rate at 24 Weeks Post Treatment (Week 48 for G2/3 and Week 72 for G1)
Description
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.
Time Frame
Week 48 for G2/3 and Week 72 for G1
Title
Number of Participants With Virological Response Rate at Weeks 12, 24, and 48 (G1 Only) During Treatment and at 12 Weeks After Treatment Completion
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
Number of Participants With > =2 Log Drop From Baseline or Undetectable HCV-RNA (<10 IU/mL) at Week 12
Time Frame
Week 12
Title
Mean Absolute Score of Beck Depression Inventory, Second Edition (BDI-II)
Description
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).
Time Frame
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).
Title
Mean Change From Baseline in BDI-II Score to EOT (Week 24/48) and EOS (Week 48/72) Visits
Description
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).
Time Frame
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)
Title
Number of Participants With Degrees of Depression as Defined by the BDI-II Score
Description
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).
Time Frame
Up to Week 72
Title
Mean Absolute Scores for Hepatitis Quality-of-Life Questionnaire (HQLQ) at EOT (Week 24/48) Visit and 24 Weeks After EOT Visit
Description
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.
Time Frame
Baseline (Day -30 to -1), 24 weeks after EOT visit (Week 48 for G2/3 and Week 72 for G1)
Title
Number of Participants With Compliance to the Prescribed Treatment Regimen
Description
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.
Time Frame
Up to Week 24 for G 2/3; up to Week 48 for G1
Title
Number of Participants With Abnormal Vital Signs
Description
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%.
Time Frame
Up to 24 weeks of treatment-free follow-up visit (Week 48 for G2/3 and Week 72 for G1)
Title
Number of Participants With Marked Laboratory Abnormalities (Hematology)
Description
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.
Time Frame
Up to 24 weeks post treatment (Week 48 for G2/3 and Week 72 for G1)
Title
Number of Participants With Marked Laboratory Abnormalities (Biochemistry)
Description
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.
Time Frame
Up to 24 weeks post treatment (Week 48 for G2/3 and Week 72 for G1)
Title
Number of Participants With Any Adverse Events (AEs), Any Serious Adverse Events (SAEs), and Study Discontinuation
Description
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.
Time Frame
Up to 24 weeks post treatment (Week 48 for G2/3 and Week 72 for G1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
City
Downers Grove
State/Province
Illinois
ZIP/Postal Code
60515
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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.

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