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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: ribavirin [Copegus]; Drug: ribavirin [Copegus]; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Santurce, Puerto Rico, 00909
• United States
  • California
    • La Jolla, California, United States, 92037-1030
    • Long Beach, California, United States, 90822
    • San Diego, California, United States, 92154
    • San Diego, California, United States, 92105
  • Connecticut
    • Farmington, Connecticut, United States, 06030
  • Florida
    • Bradenton, Florida, United States, 34209
    • Gainesville, Florida, United States, 32610-0214
    • Jacksonville, Florida, United States, 32207
    • Wellington, Florida, United States, 33414
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
  • Illinois
    • Chicago, Illinois, United States, 60612
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
  • Missouri
    • St Louis, Missouri, United States, 63104
  • New York
    • Manhasset, New York, United States, 11030
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7584
    • Statesville, North Carolina, United States, 28677
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0595
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
    • Pittsburgh, Pennsylvania, United States, 15213
  • Texas
    • Houston, Texas, United States, 77030
  • Utah
    • Salt Lake City, Utah, United States, 84121
  • Virginia
    • Charlottesville, Virginia, United States, 22906-0013
    • Richmond, Virginia, United States, 23249

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PEG-IFN Alfa-2a 180 μg +Ribavirin 1200 mg; 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]; 600mg po bid for 48 weeks; Drug: ribavirin [Copegus]; 800mg po bid for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 270 micrograms sc weekly for 48 weeks
Experimental: PEG-IFN Alfa-2a 180 μg + Ribavirin 1600 mg; 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]; 600mg po bid for 48 weeks; Drug: ribavirin [Copegus]; 800mg po bid for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 270 micrograms sc weekly for 48 weeks
Experimental: PEG-IFN Alfa-2a 270 μg + Ribavirin 1200 mg; 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]; 600mg po bid for 48 weeks; Drug: ribavirin [Copegus]; 800mg po bid for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 270 micrograms sc weekly for 48 weeks
Experimental: PEG-IFN Alfa-2a 270 μg + Ribavirin 1600 mg; 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]; 600mg po bid for 48 weeks; Drug: ribavirin [Copegus]; 800mg po bid for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: peginterferon alfa-2a (PEG-IFN alfa-2a) [Pegasys]; 270 micrograms sc weekly for 48 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: February 10, 2004
• First Submitted That Met QC Criteria: February 12, 2004
• First Posted (Estimate): February 13, 2004

Study Record Updates

• Last Update Posted (Estimate): April 18, 2016
• Last Update Submitted That Met QC Criteria: March 21, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2; Interferon-alfa-1b
• Other Study ID Numbers: NV17318