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)
Condition: Hepatitis C, Chronic; Insulin Resistance
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Insulin Resistance
Intervention: Combination of pegylated interferon alfa-2b and ribavirin; Combination of pegylated interferon alfa-2b and ribavirin
Intervention description: 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; 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
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: homeostasis model assessment of insulin resistance

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).
    

Eligibility criteria:

        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).