Study of Response in Chronic Hepatitis C (CHC) Participants Genotype 1 With Insulin Resistance and Prolonged Treatment Duration in Late Responders (P04823/MK-4031-303)

Phase 4

Terminated

Interventions: Drug: Combination of pegylated interferon alfa-2b and ribavirin

Brief Summary: This is a Phase 3b/4, prospective, open-label, randomized, multicenter study of peginterferon alfa-2b plus ribavirin in participants with chronic hepatitis C, genotype 1. The study consists of two parts: (1) a noninterventional arm (HOMA IR \<= 2) and (2) an interventional arm (HOMA IR \> 2), where HOMA IR is the insulin resistance index for the participants calculated by fasting insulin (uU/mL) x \[fasting glucose (mmol/L)/22.5\]. Participants in the noninterventional arm are treated according to the European labeling and response rates are evaluated at Month 1 (optional), 3, 6, 12, and follow up. Participants in the interventional arm are treated with PEG-Intron 1.5 ug/kg (subcutaneous) once weekly plus weight-based REBETOL 800-1400 mg (oral capsules) daily for a variable period depending on their response at Week 12: (1) HCV-RNA positive with \< 2-log drop in viral load, treatment will be discontinued; (2) HCV-RNA positive with \>= 2-log drop in viral load; participants will be randomized (1:1) to Group A (stop treatment at Week 48) or Group B (stop treatment at Week 72); and (3) HCV-RNA negative, treatment will be changed to be according to the European labeling and response rates will be evaluated at Month 6, 12, and follow up. All participants will go on with their treatment after Week 12 until the results of the HCV polymerase chain reaction (PCR) are available (maximum of 4 weeks).

Recruitment & Eligibility

Inclusion Criteria

male and female participants with newly diagnosed chronic hepatitis C
age 18-65
HCV-RNA positive in serum as measured by PCR
Genotype 1
ALT levels according to European labeling
in women of child-bearing age, pregnancy must be excluded prior to entry into the study, and the use of a safe contraceptive device must be documented; sexually active male participants must practice a method of contraception considered acceptable (vasectomy, condom plus spermicide, plus relationship with a female partner who practices an acceptable method of contraception)
Lab parameters:
- Hb: >=12 g/dL (women) or >= 13 g/dL (men)
- leukocytes >= 3,000/µL
- thrombocytes >= 100,000/µL
- PT/PTT/coagulation must be within normal limits or clinically acceptable to the investigator/sponsor
- Albumin must be within normal limits or clinically acceptable to the investigator/sponsor
- creatinine must be within normal limits or clinically acceptable to the investigator/sponsor
- uric acid must be within normal limits or clinically acceptable to the investigator/sponsor
antinuclear antibodies <= 1:160
signed informed consent

Exclusion Criteria

refusal by women of child-bearing age or by sexually active participants to use a safe contraceptive
breast-feeding women
cirrhosis stage B and C according to Child-Pugh
signs of decompensated liver disease
confirmed co-infection with HIV or HBV
existing psychiatric comorbidity
alcohol abuse
active malignant disease or suspicion or history of malignant disease within 5 previous years (except for adequately treated basal cell carcinoma)
existing psoriasis or other dermatological disorder
treatment with a study drug within the last 30 days
any uncontrolled underlying medical conditions
clinically significant ECG abnormalities and/or significant cardiovascular dysfunction within the last 6 months. In case of other suspected heart disease, a cardiological examination is required.
any liver disorder of other genesis than the study indication (with regard to elevated iron levels, only participants with manifest hemochromatosis are excluded)
autoimmune disorder (except LKM-positive participants).

Arm && Interventions

Group	Intervention	Description
Non interventional study arm (without insulin resistance)	Combination of pegylated interferon alfa-2b and ribavirin	HOMA IR \<= 2 These participants received PEG-Intron 1.5 μg /kg subcutaneously (SC) once weekly plus weight based Rebetol 800-1400 mg PO administered twice daily (BID) for 48 weeks. (Participants are treated according to European labeling).
Interventional Study arm (with insulin resistance)	Combination of pegylated interferon alfa-2b and ribavirin	HOMA IR (homeostasis model assessment-estimated insulin resistance) of \> 2 These participants received PEG-Intron 1.5 μg /kg subcutaneously (SC) once weekly plus weight based Rebetol 800-1400 mg by mouth (PO) administered twice daily (BID) for a variable period depending on their response to treatment.

Primary Outcome Measures

Name	Time	Method
Early Virological Response in Participants With and Without Insulin Resistance	At Week 12 (after start of therapy)	Early Virological Response (EVR) defined as HCV PCR at Week 12 either negative or at least 2 log units less than baseline in participants with and without insulin resistance.

Secondary Outcome Measures

Name	Time	Method
Sustained Virological Response (PCR 24 Weeks After End of Treatment)	Up to 24 weeks following 48 or 72 weeks of therapy	Sustained virological response (SVR) was defined as undetectable HCV RNA in serum at the end of follow-up (24 weeks after end of therapy) according to a polymerase chain reaction (PCR) assay.