Peg-Intron/Ribavirin in G 1 HCV for Non-Extended Versus 24 Week Extended Treatment After 24 Weeks (Study P04144)

Condition(s) targeted: Hepatitis C, Chronic

Intervention: Combination of pegylated interferon alfa-2b and ribavirin (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: Schering-Plough

Official(s) and/or principal investigator(s):
Ding-Shinn Chen, MD, Study Chair, Affiliation: Investigational Site

This is an open-label, randomized, comparative, multicenter, 48-week study designed to evaluate the efficacy and safety of combination treatment with pegylated interferon and ribavirin in adult subjects with a diagnosis of compensated chronic hepatitis C (hepatitis C virus (HCV)-ribonucleic acid (RNA) positive) (Genotype 1). All subjects will complete 24 weeks of treatment, termed the Pilot Treatment Program, after which all eligible subjects will be randomly assigned to one of two study groups. One group will be followed for an additional 48 weeks without study medication, while the other will be continuously treated for an additional 24 weeks and then followed for another 24 weeks without study medication. Sustained virologic response, defined as undetectable HCV-RNA in serum at the end of the follow-up period, will be measured along with other outcomes.

Official title: Comparison of the Sustained Response of Peg-Intron/Ribavirin Combination Therapy in Genotype 1-Infected Hepatitis C Patients for Non-Extended Versus 24-Week Extended Treatment After 24 Weeks Pilot Treatment in Taiwan

Study design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome: The proportion of individuals who are able to achieve a sustained virologic response (SVR), defined as HCV-RNA levels below assay detection 24 weeks after termination of anti-HCV therapy

Secondary outcome: The proportion of individuals who are able to achieve a virologic response 48 weeks after randomization.

Detailed description: This is an open-label, randomized, comparative, multicenter study for evaluation of Peg-Intron/Ribavirin therapy in the efficacy and safety in adult subjects with a diagnosis of compensated chronic hepatitis C (HCV-RNA+) (Genotype 1). This is a 48-week study, for which all subjects should participate in the Pilot Treatment Program and complete 24 weeks treatment. To avoid a treatment gap, subjects who will be screened and eligible subjects will sign informed consent prior to the end of the Pilot Treatment Program. After completion of the Pilot Treatment Program, all eligible subjects will be randomly assigned to either study group. Subjects of Group 1 will be followed-up without study medication for 48 weeks; Group 2 will be continuously treated for another 24 weeks and all subjects of Group 2 will be followed for another 24 weeks after completion of the treatment period. Subjects of both groups will be evaluated at screening, randomization, 4, 8, 12, 16, 20, 24, 28, 36 and 48 weeks after randomization.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subject must be willing to give written informed consent and be able to adhere to dose

and visit schedules.

- Males and non-pregnant females and aged >= 18 years, subjects who are over 65 years of

age must be in generally good health and must be discussed with and approved by the principal investigator prior to entry.

- The laboratory evaluation within 6 months prior to entering the Pilot Treatment

Program must meet the following criteria:

- Hemoglobin values of >= 12 g/dL for females and >= 13 g/dL for males

- Neutrophil count >= 1. 5 X109/L

- Platelets count >= 100 x 109/L

- Total bilirubin < 1. 5 mg/dL

- Serum creatinine within normal limits

- Positive serum HCV-RNA (>= 50 IU (100 copy numbers)/mL)

- Anti-HCV positive

- Available HCV genotype 1

- Liver biopsy performed within 12 months prior to entry to this protocol with a

pathology report confirming that the histological diagnosis is consistent with chronic hepatitis (METAVIR system >=F1).

- Compensated liver disease with the following hematological, biochemical, and serologic

criteria at the screening visit:

- Hemoglobin values of >= 9 g/dL

- Neutrophil count >= 0. 75 x 109/L

- Platelets count >= 50 x 109/L

- PT prolong <= 3 sec, INR <= 1. 2

- Total bilirubin <= 3 mg/dL

- Within normal limits (subjects requiring medication to maintain TSH levels in the

normal range are eligible if all other inclusion/exclusion criteria are met).

- Anti-HIV negative.

- AFP value within normal limits obtained within 12 months prior to entry. Results above

the upper limit of normal but <= 50 ng/mL require both of the following:

- AFP value <= 50 ng/mL obtained within 9 months prior to entry in the study or during

the Screening period, and Ultrasound obtained within 9 months prior to entry or in the screening period in the study for evidence of not having hepatocellular carcinoma.

- A urine pregnancy test obtained prior to the initiation of pilot treatment must be

negative. Female subjects must not be breast feeding.

- Reconfirmation that sexually-active subjects are practicing acceptable methods of

contraception during screening period.

- Complete 24 weeks treatment of the Pilot Treatment Program with Peg-Intron +

Ribavirin.

- Must be never treated with interferon for HCV infected hepatitis (treatment naïve)

before the Pilot Treatment Program.

- The total amount of Peg-Intron and Ribavirin received during the pilot treatment

program must achieve more than 80% of the recommended dosage.

Exclusion Criteria:

- Women who are pregnant or nursing.

- Have decompensated cirrhosis.

- History of severe psychiatric disease, especially depression.

- Concurrent malignancies (including hepatocellular carcinoma).

- Unstable or significant cardiovascular diseases. Subjects with (ECG) showing

clinically significant abnormalities.

- Prolonged exposure to known hepatotoxins such as alcohol or drugs.

- History of thyroid disease poorly controlled on prescribed medication.

- Poorly controlled diabetes mellitus.

- Has suspected or confirmed significant hepatic disease from an etiology other than

HCV.

- Patients co-infected with hepatitis B and /or human immunodeficiency virus (HIV).

- Severe renal disease or myeloid dysfunction.

- History of organ transplantation other than cornea and hair transplant.

- Any medical condition requiring, or likely to require during the course of the study,

chronic systemic administration of steroids.

- Any other condition which in the opinion of the investigator would make the subject

unsuitable for enrollment, or could interfere with the subject participating in and completing the protocol.

- Allergy to interferon.

Investigational Site 1, Taipei 100, Taiwan

Investigational Site 3, Taipei 112, Taiwan

Investigational Site 4, Taipei 112, Taiwan

Investigational Site 6, Tainan 704, Taiwan

Investigational Site 7, Kaoshiung 833, Taiwan

Investigational Site 8, Kaoshiung 807, Taiwan

Investigational Site 9, Kaoshiung 813, Taiwan

Investigational Site 10, Kaoshiung 812, Taiwan

Investigational Site 2, Taoyuan county 333, Taiwan

Investigational Site 5, Taipei 114, Taiwan

Starting date: March 2005
Ending date: July 2008
Last updated: June 16, 2008