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)

NCT ID: NCT00493805

Last Updated: 2017-04-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2009-10-31

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).

Conditions

Hepatitis C, Chronic; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional Study arm (with insulin resistance)

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.

Group Type: EXPERIMENTAL

Combination of pegylated interferon alfa-2b and ribavirin

Intervention Type: DRUG

1. 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.

2. 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

Non interventional study arm (without insulin resistance)

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).

Group Type: EXPERIMENTAL

Combination of pegylated interferon alfa-2b and ribavirin

Intervention Type: DRUG

1. Powder for injection in Redipen (50, 80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for 48 weeks

2. 200 mg capsules, oral, weight based dose of 800-1400 mg, daily for 48 weeks

Interventions

Combination of pegylated interferon alfa-2b and ribavirin

1. 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.

2. 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

Intervention Type: DRUG

Combination of pegylated interferon alfa-2b and ribavirin

1. Powder for injection in Redipen (50, 80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for 48 weeks

2. 200 mg capsules, oral, weight based dose of 800-1400 mg, daily for 48 weeks

Intervention Type: DRUG

Other Intervention Names

(a) SCH 54031, PEG-Intron; (b) SCH 18908, Rebetol; (a) SCH 54031, PEG-Intron; (b) SCH 18908, Rebetol

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

EudraCT number:2006-000757-21

Identifier Type: -

Identifier Source: secondary_id

P04823

Identifier Type: -

Identifier Source: org_study_id