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)

Study Overview
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Brief Summary
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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).

Official Title
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Study to Evaluate Response Rates in Chronic Hepatitis C (CHC) Patients Genotype 1 With Insulin Resistance and to Assess Prolonged Treatment Duration in Late Virological Responders

Conditions
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Hepatitis C, Chronic, Insulin Resistance

Intervention / Treatment
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* Drug: Combination of pegylated interferon alfa-2b and ribavirin
* Drug: Combination of pegylated interferon alfa-2b and ribavirin


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional Study arm (with insulin resistance)<br>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. | Drug: Combination of pegylated interferon alfa-2b and ribavirin<br>* Powder for injection in Redipen (50, 80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for 12 weeks, then up to 4 weeks until HCV PCR results are available, and then for another 36 weeks(Group A) or 60 weeks (Group B) postrandomization. 200 mg capsules, oral, weight based dose of 800-1400 mg, daily for up to 12 weeks, then up to 4 weeks until HCV PCR results are available, and then for another 36 weeks (Group A) or 60 weeks (Group B) postrandomization<br>* Other names: (b) SCH 18908, Rebetol;|
| Experimental: Non interventional study arm (without insulin resistance)<br>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). | Drug: Combination of pegylated interferon alfa-2b and ribavirin<br>* Powder for injection in Redipen (50, 80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for 48 weeks 200 mg capsules, oral, weight based dose of 800-1400 mg, daily for 48 weeks<br>* Other names: (b) SCH 18908, Rebetol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Virological Response in Participants With and Without Insulin Resistance | 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. | At Week 12 (after start of therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (PCR 24 Weeks After End of Treatment) | 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. | Up to 24 weeks following 48 or 72 weeks of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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homeostasis model assessment of insulin resistance