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Study of PEG-Intron Plus REBETOL in Pediatric Subjects With Chronic Hepatitis C (Study P02538 Part 1)

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
peginterferon alfa-2b (PEG2b) (SCH 54031)
ribavirin (SCH 18908)
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic

Eligibility Criteria

3 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Children age 3-17 years old Individuals weighing ≤ 90 kg Previously untreated children with chronic hepatitis C (HCV RNA qPCR plasma positive) Individuals with any HCV (hepatitis C virus) genotype Hematology laboratory results of: Hemoglobin (HGB) ≥ 11 g/dL for females or ≥ 12g/dL for males, White Blood Cell Count (WBC) ≥ 3,000/mm^3, Neutrophils ≥ 1,500/mm^3, Platelets ≥ 100,000/mm^3 Chemistry laboratory results of: Normal Thyroid Stimulating Hormone (TSH), albumin, creatinine, and Bilirubin, Antinuclear antibody (ANA) ≤ 1:160, Fasting Glucose 70-140 mg/dL. Note: If glucose levels are between 116-140 mg/dL or an individual has diabetes, HbA1C must be ≤ 8.5% Compensated liver disease Historic or pre-treatment liver biopsy slides available No significant co-existing psychiatric disease Those with diabetes, hypertension, or birth prior to 32 weeks gestational age must have normal eye exams and retinal photographs (these will be done as part of the study before hepatitis C treatment is given) Patients and partners of patients willing to use adequate contraception during the course of the study Abstain from alcohol and any other illicit drugs Exclusion Criteria: Serum ALT >10 times the upper limit of normal within the 6 months prior to study Previous hepatitis C treatment Children with liver disease not caused by hepatitis C Most recent liver biopsy is normal Individuals infected with the hepatitis B virus and/or human immunodeficiency virus (HIV) Known blood disorders such as hemoglobinopathy, coagulopathy, or G6PD deficiency Known immunodeficiency disorders requiring immunoglobulin therapy Body organ transplant Any known or suspected cancer within the past 5 years Children with chronic pulmonary disease Individuals who have a medical condition that would likely require systemic steroids Those with a history of central nervous system (CNS) trauma or seizure disorders Individuals with pre-existing psychiatric disorders including but not limited to moderate to severe depression Current or previous use of lithium or antipsychotic drugs Patients with clinically significant electrocardiogram (ECG) abnormalities and/or significant cardiovascular dysfunction (e.g., angina, congestive heart failure, recent myocardial infarction, uncontrolled hypertension, significant arrhythmia, cardiac sequelae from Kawasaki disease, cardiomyopathy, and/or history of congenital heart disease) Insulin-dependent diabetes mellitus or poorly controlled non-insulin dependent diabetes mellitus Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, or symptomatic thyroid disorder) History of substance abuse, including alcohol (e.g., binge drinking, blackouts), intravenous drugs and inhaled drugs Subjects who have a history of pregnancy or who are pregnant and/or breast feeding. Subjects who intend to become pregnant during the study period. Subjects with partners who intend to become pregnant during the study period Subjects with clinically significant retinal abnormalities such as known retinopathy of prematurity or other retinopathies

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    PEG-Intron alfa 2b (PEG2b) plus REBETOL (RBV)

    Arm Description

    PEG2b 1.5 μg/kg/wk given subcutaneously (once weekly) and RBV 400-1200 mg/day by mouth divided in 2 daily doses (administered twice daily with food, dosed 12 hours apart) for 48 weeks. Subjects treated up to 48 weeks and followed for additional 24 weeks after the end of treatment (total of 72 weeks study participation).

    Outcomes

    Primary Outcome Measures

    Number of Participants With a Sustained Virologic Response (SVR) at 24 Weeks Post-treatment
    SVR is defined as undetectable hepatitis C virus ribonucleic acid (HCV-RNA) at 24 weeks post-treatment

    Secondary Outcome Measures

    Full Information

    First Posted
    February 22, 2005
    Last Updated
    March 7, 2017
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00104052
    Brief Title
    Study of PEG-Intron Plus REBETOL in Pediatric Subjects With Chronic Hepatitis C (Study P02538 Part 1)
    Official Title
    Assessment of the Safety, Efficacy, Tolerability and Pharmacokinetics of PEG-Intron® Plus REBETOL® in Pediatric Patients With Chronic Hepatitis C
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    February 2005 (undefined)
    Primary Completion Date
    November 2007 (Actual)
    Study Completion Date
    November 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The primary objective is to assess the safety, efficacy and tolerability of the combination of PEG-Intron plus REBETOL in pediatric subjects with chronic hepatitis C. The secondary objective is to measure the multiple-dose pharmacokinetics of PEG-Intron and REBETOL in pediatric subjects with chronic hepatitis C.
    Detailed Description
    This global, multicenter, open-label Phase 3 study will evaluate the safety, efficacy and tolerability of PEG-Intron plus REBETOL in previously untreated pediatric subjects, ages 3 through 17 years, with chronic hepatitis C.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis C, Chronic

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    107 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    PEG-Intron alfa 2b (PEG2b) plus REBETOL (RBV)
    Arm Type
    Experimental
    Arm Description
    PEG2b 1.5 μg/kg/wk given subcutaneously (once weekly) and RBV 400-1200 mg/day by mouth divided in 2 daily doses (administered twice daily with food, dosed 12 hours apart) for 48 weeks. Subjects treated up to 48 weeks and followed for additional 24 weeks after the end of treatment (total of 72 weeks study participation).
    Intervention Type
    Biological
    Intervention Name(s)
    peginterferon alfa-2b (PEG2b) (SCH 54031)
    Other Intervention Name(s)
    PEG-Intron (SCH 54031)
    Intervention Description
    PEG2b 1.5 μg/kg/wk given subcutaneously (once weekly) for 48 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    ribavirin (SCH 18908)
    Other Intervention Name(s)
    REBETOL (SCH 18908)
    Intervention Description
    15 mg/kg/day for up to 48 weeks
    Primary Outcome Measure Information:
    Title
    Number of Participants With a Sustained Virologic Response (SVR) at 24 Weeks Post-treatment
    Description
    SVR is defined as undetectable hepatitis C virus ribonucleic acid (HCV-RNA) at 24 weeks post-treatment
    Time Frame
    Up to 48-week treatment duration. Follow-up of 24 weeks.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Years
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Children age 3-17 years old Individuals weighing ≤ 90 kg Previously untreated children with chronic hepatitis C (HCV RNA qPCR plasma positive) Individuals with any HCV (hepatitis C virus) genotype Hematology laboratory results of: Hemoglobin (HGB) ≥ 11 g/dL for females or ≥ 12g/dL for males, White Blood Cell Count (WBC) ≥ 3,000/mm^3, Neutrophils ≥ 1,500/mm^3, Platelets ≥ 100,000/mm^3 Chemistry laboratory results of: Normal Thyroid Stimulating Hormone (TSH), albumin, creatinine, and Bilirubin, Antinuclear antibody (ANA) ≤ 1:160, Fasting Glucose 70-140 mg/dL. Note: If glucose levels are between 116-140 mg/dL or an individual has diabetes, HbA1C must be ≤ 8.5% Compensated liver disease Historic or pre-treatment liver biopsy slides available No significant co-existing psychiatric disease Those with diabetes, hypertension, or birth prior to 32 weeks gestational age must have normal eye exams and retinal photographs (these will be done as part of the study before hepatitis C treatment is given) Patients and partners of patients willing to use adequate contraception during the course of the study Abstain from alcohol and any other illicit drugs Exclusion Criteria: Serum ALT >10 times the upper limit of normal within the 6 months prior to study Previous hepatitis C treatment Children with liver disease not caused by hepatitis C Most recent liver biopsy is normal Individuals infected with the hepatitis B virus and/or human immunodeficiency virus (HIV) Known blood disorders such as hemoglobinopathy, coagulopathy, or G6PD deficiency Known immunodeficiency disorders requiring immunoglobulin therapy Body organ transplant Any known or suspected cancer within the past 5 years Children with chronic pulmonary disease Individuals who have a medical condition that would likely require systemic steroids Those with a history of central nervous system (CNS) trauma or seizure disorders Individuals with pre-existing psychiatric disorders including but not limited to moderate to severe depression Current or previous use of lithium or antipsychotic drugs Patients with clinically significant electrocardiogram (ECG) abnormalities and/or significant cardiovascular dysfunction (e.g., angina, congestive heart failure, recent myocardial infarction, uncontrolled hypertension, significant arrhythmia, cardiac sequelae from Kawasaki disease, cardiomyopathy, and/or history of congenital heart disease) Insulin-dependent diabetes mellitus or poorly controlled non-insulin dependent diabetes mellitus Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, or symptomatic thyroid disorder) History of substance abuse, including alcohol (e.g., binge drinking, blackouts), intravenous drugs and inhaled drugs Subjects who have a history of pregnancy or who are pregnant and/or breast feeding. Subjects who intend to become pregnant during the study period. Subjects with partners who intend to become pregnant during the study period Subjects with clinically significant retinal abnormalities such as known retinopathy of prematurity or other retinopathies

    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
    Citations:
    PubMed Identifier
    27111344
    Citation
    Haber B, Alonso E, Pedreira A, Rodriguez-Baez N, Ciocca M, Lacaille F, Lang T, Gonzalez T, Goodman Z, Yang Z, Jackson B, Noviello S, Albrecht JK. Long-Term Follow-Up of Children Treated With Peginterferon and Ribavirin for Hepatitis C Virus Infection. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):89-94. doi: 10.1097/MPG.0000000000001239.
    Results Reference
    derived
    PubMed Identifier
    20189674
    Citation
    Wirth S, Ribes-Koninckx C, Calzado MA, Bortolotti F, Zancan L, Jara P, Shelton M, Kerkar N, Galoppo M, Pedreira A, Rodriguez-Baez N, Ciocca M, Lachaux A, Lacaille F, Lang T, Kullmer U, Huber WD, Gonzalez T, Pollack H, Alonso E, Broue P, Ramakrishna J, Neigut D, Valle-Segarra AD, Hunter B, Goodman Z, Xu CR, Zheng H, Noviello S, Sniukiene V, Brass C, Albrecht JK. High sustained virologic response rates in children with chronic hepatitis C receiving peginterferon alfa-2b plus ribavirin. J Hepatol. 2010 Apr;52(4):501-7. doi: 10.1016/j.jhep.2010.01.016. Epub 2010 Feb 4.
    Results Reference
    derived

    Learn more about this trial

    Study of PEG-Intron Plus REBETOL in Pediatric Subjects With Chronic Hepatitis C (Study P02538 Part 1)

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