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)

This study has been terminated.
(Slow Enrollment)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00493805
First received: June 25, 2007
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Hepatitis C, Chronic
Insulin Resistance
Drug: Combination of pegylated interferon alfa-2b and ribavirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Early Virological Response in Participants With and Without Insulin Resistance [ Time Frame: At Week 12 (after start of therapy) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 24 weeks following 48 or 72 weeks of therapy ] [ Designated as safety issue: No ]
    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.


Enrollment: 59
Study Start Date: April 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

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 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
Other Names:
  • (a) SCH 54031, PEG-Intron
  • (b) SCH 18908, Rebetol
Experimental: 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).

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
Other Names:
  • (a) SCH 54031, PEG-Intron
  • (b) SCH 18908, Rebetol

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00493805     History of Changes
Other Study ID Numbers: P04823, EudraCT number:2006-000757-21
Study First Received: June 25, 2007
Results First Received: October 27, 2010
Last Updated: July 28, 2014
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Merck Sharp & Dohme Corp.:
homeostasis model assessment of insulin resistance

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Insulin Resistance
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Interferon-alpha
Interferons
Ribavirin
Peginterferon alfa-2b
Insulin, Globin Zinc
Insulin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Hypoglycemic Agents

ClinicalTrials.gov processed this record on August 27, 2014