Back to resultsStudy of Response in Chronic Hepatitis C (CHC) Participants Genotype 1 With Insulin Resistance and Prolonged Treatment Duration in Late Responders (P04823/MK-4031-303)
Primary Purpose
Hepatitis C, Chronic, Insulin Resistance
Status
Terminated
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Combination of pegylated interferon alfa-2b and ribavirin
Combination of pegylated interferon alfa-2b and ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring homeostasis model assessment of insulin resistance
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).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Interventional Study arm (with insulin resistance)
Non interventional study arm (without insulin resistance)
Arm Description
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.
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00493805
Brief Title
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)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Slow Enrollment
Study Start Date
April 2007 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic, Insulin Resistance
Keywords
homeostasis model assessment of insulin resistance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Interventional Study arm (with insulin resistance)
Arm Type
Experimental
Arm Description
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.
Arm Title
Non interventional study arm (without insulin resistance)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Combination of pegylated interferon alfa-2b and ribavirin
Other Intervention Name(s)
(a) SCH 54031, PEG-Intron, (b) SCH 18908, Rebetol
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
Intervention Type
Drug
Intervention Name(s)
Combination of pegylated interferon alfa-2b and ribavirin
Other Intervention Name(s)
(a) SCH 54031, PEG-Intron, (b) SCH 18908, Rebetol
Intervention Description
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
Primary Outcome Measure Information:
Title
Early Virological Response in Participants With and Without Insulin Resistance
Description
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.
Time Frame
At Week 12 (after start of therapy)
Secondary Outcome Measure Information:
Title
Sustained Virological Response (PCR 24 Weeks After End of Treatment)
Description
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.
Time Frame
Up to 24 weeks following 48 or 72 weeks of therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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).
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
Learn more about this trial
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)
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