Extended Treatment With PEG-Intron® and Rebetol® in Patients With Genotype 1 Chronic Hepatitis C and Slow Virologic Response (Study P03685)

March 8, 2017 updated by: Merck Sharp & Dohme LLC

A Study to Assess Treatment With PEG-Intron® and Rebetol® in Naïve Patients With Genotype 1 Chronic Hepatitis C and Slow Virological Response

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

1428

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard therapy
Slow responders (defined as being polymerase chain reaction [PCR] positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to stop treatment at Week 48.
  1. 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
  2. 200 mg capsules, oral, weight based dose of 800-1400 mg, daily for 48 weeks
Other Names:
  • (a) SCH 54031; PEG-Intron; PegIntron; ViraferonPeg.
  • (b) SCH 18908; Rebetol; REBETOL.
Experimental: Extended therapy
Slow responders (defined as being PCR positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to continue treatment to Week 72.
  1. 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.
  2. 200 mg capsules, oral, weight based dose of 800-1400 mg, daily for 72 weeks
Other Names:
  • (a) SCH 54031; PEG-Intron; PegIntron; ViraferonPeg.
  • (b) SCH 18908; Rebetol; REBETOL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sustained Virologic Response, Defined as a Plasma HCV-RNA (Hepatitis C Ribonucleic Acid) Level Below the LLQ (Lower Level of Quantitation) at 24 Weeks Post-treatment.
Time Frame: 48 or 72 weeks of treatment plus 24 weeks of follow-up.
LLQ = 30 IU/mL by reverse transcription polymerase chain reaction (RT-PCR) (Taqman Roche)
48 or 72 weeks of treatment plus 24 weeks of follow-up.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2004

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

December 13, 2005

First Submitted That Met QC Criteria

December 13, 2005

First Posted (Estimate)

December 14, 2005

Study Record Updates

Last Update Posted (Actual)

April 5, 2017

Last Update Submitted That Met QC Criteria

March 8, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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