Extended Treatment With PEG-Intron® and Rebetol® in Patients With Genotype 1 Chronic Hepatitis C and Slow Virologic Response (Study P03685)
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: Combination of pegylated interferon alfa-2b (PEG-Intron®) and ribavirin (Rebetol®); Combination of pegylated interferon alfa-2b and ribavirin
Intervention description: Powder for injection in vial or 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; Powder for injection in vial or Redipen (50, 80, 100, 120, and 150 microgram strength), subcutaneous, dose of 1.5 micrograms/kg, weekly for 72 weeks.
200 mg capsules, oral, weight based dose of 800-1400 mg, daily for 72 weeks
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1428.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This is a controlled, randomized, parallel-groups, open-label, multinational study designed
      to evaluate the efficacy and safety of PEG-Intron® (pegylated interferon alfa-2b) plus
      Rebetol® (ribavirin) in subjects with chronic hepatitis C. It is designed to evaluate whether
      72 weeks of treatment with PEG-Intron plus Rebetol is more effective than 48 weeks of
      treatment in subjects with Genotype 1 chronic hepatitis C who exhibit a slow response to
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult subjects aged 18 to 70 years, of either sex.

          -  Genotype-1 hepatitis C virus (HCV)-ribonucleic acid (RNA)-positive subjects.

          -  Subjects must be willing to give written informed consent and able to adhere to dosing
             and visit schedules.

          -  Confirmation of liver biopsy availability: Availability of a liver biopsy performed
             within 18 months prior to the Screen visit, with a pathology report confirming the
             histological diagnosis of chronic hepatitis or liver cirrhosis.

          -  Compensated liver disease with the following minimum hematological, biochemical, and
             serological criteria at the screen visit (WNL = within normal limits, ULN = Upper
             Limit Normal):

               -  Hemoglobin values of equal or more than 12 g/dL for females and 13 g/dL for
                  males.

               -  White blood cells (WBCs) equal to or more than 3,000/mm^3

               -  Neutrophil count equal to or more than 1,500/mm^3

               -  Platelet count equal to or more than 80,000/mm^3

               -  Direct bilirubin up to 10% above ULN is acceptable.

               -  Indirect bilirubin up to 10% above ULN is acceptable (unless non-hepatitis
                  related factors such as Gilbert's disease explain an indirect bilirubin rise). In
                  such cases indirect bilirubin should be less than or equal to 3.0 mg/dL (less
                  than or equal to 51.3 µmol/L)

               -  Albumin up to 10% above ULN is acceptable.

               -  Serum creatinine up to 10% above ULN is acceptable.

               -  Alanine aminotransferase (ALT) level above ULN at Screen.

          -  At the Screen Visit, fasting glucose must be 70-140 mg/dL. Results between 116-140
             mg/dL require repeat fasting glucose to be less than 140 mg/dL and HbA1C less than or
             equal to 8.5%. HbA1C must be less than or equal to 8.5% in diabetic subjects (whether
             on medication or diet controlled).

          -  Antinuclear antibodies (ANA) must be less than or equal to 1:320.

          -  Thyroid Stimulating Hormone (TSH) WNL whether in euthyroid subjects or subjects
             requiring medical treatment. (subjects requiring medication to maintain TSH levels
             within normal limits are eligible if all other inclusion/exclusion criteria are met).

          -  Confirmation by the principal investigator or a sub-investigator that sexually active
             females of childbearing potential are practicing adequate contraception.

          -  Female subjects cannot be pregnant or breastfeeding and must be either postmenopausal,
             surgically sterile or using 2 methods of birth control. While abstinence from sexual
             activity is the only certain method to prevent pregnancy, female patients of
             childbearing potential who are or who anticipate the possibility of becoming sexually
             active with a male partner must use a combination of the following 2 methods :

               -  Contraceptive pill or intrauterine device (IUD) or depot hormonal preparation
                  (ring, injection implant) and

               -  A barrier method of contraception such as diaphragm, sponge with spermicide,
                  condom, or a method of birth control considered acceptable by the study
                  physician. Contraceptive measures will be reviewed with female subjects at each
                  visit. Dual methods of contraception must be used for 1 month prior to the start
                  of treatment and 6 months after treatment discontinuation.

          -  A serum pregnancy test obtained at Screen Visit prior to the initiation of treatment
             must be negative.

          -  Confirmation by the principal investigator or a sub-investigator that sexually active
             male subjects are practicing a method of contraception considered acceptable
             (vasectomy, condom plus spermicide, plus relationship with a female partner who
             practices an acceptable method of contraception). Contraception must be used during
             the treatment period and for seven months (or 6 months, according to local label)
             after the completion of therapy, including condom use by male subjects with pregnant
             partners.

          -  For subjects with a history of hypertension or diabetes, written clearance from an
             ophthalmologist has to be obtained prior to treatment start.

        Exclusion Criteria:

          -  Pregnant women, women who plan to become pregnant, male subjects whose partner wants
             to become pregnant, and breastfeeding women.

          -  Previous treatment for chronic hepatitis C with an antiviral or immunomodulating agent
             or with some interferon or ribavirin product, whether alone or in combination.

          -  Subjects weighing over 125 kg.

          -  Suspected hypersensitivity to any interferon or ribavirin product.

          -  Participation in other clinical trial within 30 days prior to screen into this study.

          -  Coinfection with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or both.

          -  Any cause of liver disease other than chronic hepatitis C, including but not limited
             to:

               -  Hemochromatosis

               -  Alpha-1 antitrypsin deficiency

               -  Wilson's disease

               -  Autoimmune hepatitis

               -  Alcoholic liver disease

               -  Non-alcoholic steatohepatitis (NASH)

               -  Drug-related liver disease

          -  Active malignant disease or suspicion or history of malignant disease within five
             previous years (except for adequately treated basal cell carcinoma).

          -  Known coagulation diseases such as hemophilia; hemoglobin diseases (e.g. thalassemia).

          -  Known glucose 6-phosphate dehydrogenase (G6PD) deficiency

          -  Evidence of advanced liver disease such as history or presence of ascites, bleeding
             varices, or hepatic encephalopathy.

          -  Subjects with organ transplants, except for corneal or hair transplant.

          -  Any known preexisting medical condition that could interfere with the subject's
             participation in and completion of study, such as:

               -  Preexisting psychiatric condition, especially moderate to severe depression, or a
                  history of severe psychiatric disorder, such as psychosis, suicidal ideation, or
                  suicide attempts. Severe depression includes the following:

                    -  Hospitalization for depression

                    -  Electroconvulsive therapy for depression, or

                    -  Depression causing a prolonged absence from work or significantly altering
                       daily functions.

               -  Subjects with mild depression may be considered for entry into the study provided
                  that a pre-treatment assessment demonstrates that the subject's emotional status
                  is clinically stable, in which case a management plan must be formulated for the
                  subject; this management plan will become a part of the subject's medical record.

               -  Craniocerebral trauma which is not a concussion, or active seizure disorders
                  requiring medication.

               -  Clinically significant electrocardiogram (ECG) abnormalities and/or
                  cardiovascular dysfunction within 6 previous months (e.g., angina, congestive
                  heart failure, recent myocardial infarction, or significant arrhythmia).

               -  Chronic lung disease (e.g., chronic obstructive lung disease)

               -  Poorly controlled diabetes mellitus

               -  Immune-mediated disease (e.g., inflammatory bowel disease [Crohn's disease,
                  ulcerative colitis], idiopathic thrombocytopenic purpura, systemic lupus
                  erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis)

               -  Clinical gout

          -  Subject is or was a substance abuser, such as alcohol (80 g/day or more), methadone,
             intravenous(IV), oral or inhaled drugs. To be considered for inclusion into the
             protocol, the subject must have abstained and agree to abstain from using any of the
             above for at least 6 months. Subjects treated with buprenorphine (Subutex) who have
             been stable for 6 months may be included.

          -  Cirrhotic subjects whose ultrasound confirms hepatocellular carcinoma.

          -  Any other condition that, in the investigator's opinion, could determine that
             subject's participation in the study is not indicated or could interfere with the
             subject's participation in and completion of study.

          -  Subjacent disease that potentially would require systematic administration of steroids

          -  Insulin dependent diabetes mellitus