PEDS-C: Pegylated Interferon +/- Ribavirin for Children With Hepatitis C

NCT00100659 | Completed Phase 3 Results

• 2 other identifiers: 67767 (completed)U01DK067767
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to determine the safety and efficacy of peginterferon alfa-2a (PEG-2a) in combination with ribavirin (RV) and PEG-2a alone for the treatment of chronic hepatitis C virus (CHC) infection in children. The purpose of this study is also to determine whether PEG-2a in combination with RV or PEG-2a alone will result in a longer response rate in children with CHC.

Conditions

Chronic Hepatitis C

Keywords

pediatric; hepatitis; children; HCV; PEG; PEG-2a; peginterferon alfa-2a; Pegylated Interferon; RV; ribavirin; Pegasys; CHC; chronic hepatitis C; chronic hepatitis C virus; hepatitis c; pediatric hepatitis; pediatric HCV

Outcome Measures

Primary Outcomes (1)

• Sustained Viral Response (SVR)

  SVR is defined as nondetectable hepatitis C virus ribonucleic acid (HCV RNA) in plasma

  at least 24 weeks after stopping treatment.

Secondary Outcomes (1)

• Adverse Events

  At any time up to 72 weeks

Study Arms (2)

Pegylated interferon/ribavirin

ACTIVE COMPARATOR

Pegasys - 180 mcg per 1.73 meter squared body surface area subcutaneously once weekly. Ribavirin - 15 mg per kg orally twice daily using 100-mg tablets.

Drug: Pegylated Interferon/ribavirin

Pegylated interferon/placebo

PLACEBO COMPARATOR

Placebo tablets were supplied in the same dosing regimen as ribavirin, using the same number of tablets that would be given if ribavirin were being administered (eg, 3 placebo tablets twice daily for a 40-kg child who would receive 3 100-mg RV tablets twice daily).

Drug: Pegylated Interferon/ribavirin

Interventions

Pegylated Interferon/ribavirin DRUG

Pegylated interferon/placebo; Pegylated interferon/ribavirin

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female patients who are 5-18 years of age at enrollment (not yet reached 18th birthday at screening).
• HCV viremia (by any test) present on 2 tests separated by at least 6 months.
• Chronic liver disease, as indicated by inflammation and/or fibrosis, consistent with chronic hepatitis C infection on a liver biopsy obtained within the past 24 months, as assessed by a qualified pathologist, not consistent with other known liver disease and not normal.
• Compensated liver disease (Child-Pugh Grade A clinical classification)
• Signed informed consent from parent/legal guardian and willingness of parent/legal guardian to abide by the requirements of the study.
• Hemoglobin values \>11 g/dL for females; \> 12 g/dL for males
• Normal thyroid stimulating hormone (TSH)
• Able to swallow a ribavirin/placebo tablet

You may not qualify if:

• Any prior treatment with Interferon or ribavirin (RV)
• Receipt of any investigational drug \<6 weeks prior to the first dose of study drug
• Any systemic antiviral therapy \<6 weeks prior to the first dose of study drug. Exception: patients who have taken or are expected to require acyclovir for herpetic lesions
• Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or anti-HIV Ab
• History or other evidence of a medical condition associated with chronic liver disease other than HCV (abnormal ceruloplasmin, alpha-1-antitrypsin, ANA\>1:160, SMA\>1:80, anti-LKM antibody \> 60 units))
• History or other evidence of bleeding from esophageal varices
• Decompensated liver disease (e.g. conjugated bilirubin \>1.5mg/dl, ascites, varices, Child-Pugh Grade B or C clinical classification)
• History of autoimmune or immunologically mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, clinical evidence of rheumatoid arthritis)
• Absolute neutrophil count \<1500 cells/mm3 , hemoglobin \<11 g/dL for females and \<12 g/dL for males, white blood count\>17.5 x 109/L, or platelet count \<90,000/ mm3
• Serum creatinine level \>1.5 times the upper limit of normal for age
• Major depression according to the American Psychiatric Association, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicide attempt
• History or other evidence of chronic pulmonary or cardiac disease associated with functional limitation
• History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded
• Poorly controlled diabetes as defined by glycosylated hemoglobin of \> 8%
• History of solid organ or bone marrow transplantation

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Roche Pharma AG: collaborator

Study Sites (11)

University of California, San Francisco

San Francisco, California, 94143-0136, United States

Location

The Children's Hospital

Denver, Colorado, 80218, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Indiana University School of Medicine, James Whitcomb Riley Hospital for Children

Indianapolis, Indiana, 46202-5225, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital and Regional Medical Center

Seattle, Washington, 98105, United States

Location

Related Publications (9)

• Murray KF, Rodrigue JR, Gonzalez-Peralta RP, Shepherd J, Barton BA, Robuck PR, Schwarz KB; PEDS-C Clinical Research Network. Design of the PEDS-C trial: pegylated interferon +/- ribavirin for children with chronic hepatitis C viral infection. Clin Trials. 2007;4(6):661-73. doi: 10.1177/1740774507085445.

  PMID: 18042575 BACKGROUND

• Rodrigue JR, Balistreri W, Haber B, Jonas MM, Mohan P, Molleston JP, Murray KF, Narkewicz MR, Rosenthal P, Smith LJ, Lobritto SJ, Schwarz KB, Robuck PR, Barton B, Gonzalez-Peralta RP. Peginterferon with or without ribavirin has minimal effect on quality of life, behavioral/emotional, and cognitive outcomes in children. Hepatology. 2011 May;53(5):1468-75. doi: 10.1002/hep.24248.

  PMID: 21351116 RESULT

• Schwarz KB, Gonzalez-Peralta RP, Murray KF, Molleston JP, Haber BA, Jonas MM, Rosenthal P, Mohan P, Balistreri WF, Narkewicz MR, Smith L, Lobritto SJ, Rossi S, Valsamakis A, Goodman Z, Robuck PR, Barton BA; Peds-C Clinical Research Network. The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C. Gastroenterology. 2011 Feb;140(2):450-458.e1. doi: 10.1053/j.gastro.2010.10.047. Epub 2010 Oct 28.

  PMID: 21036173 RESULT

• Goodman ZD, Makhlouf HR, Liu L, Balistreri W, Gonzalez-Peralta RP, Haber B, Jonas MM, Mohan P, Molleston JP, Murray KF, Narkewicz MR, Rosenthal P, Smith LJ, Robuck PR, Schwarz KB. Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial. Hepatology. 2008 Mar;47(3):836-43. doi: 10.1002/hep.22094.

  PMID: 18167062 RESULT

• Narkewicz MR, Rosenthal P, Schwarz KB, Drack A, Margolis T, Repka MX; PEDS-C Study Group. Ophthalmologic complications in children with chronic hepatitis C treated with pegylated interferon. J Pediatr Gastroenterol Nutr. 2010 Aug;51(2):183-6. doi: 10.1097/MPG.0b013e3181b99cf0.

  PMID: 20512062 RESULT

• Delgado-Borrego A, Gonzalez-Peralta RP, Raza R, Negre B, Goodman ZD, Jonas MM, Chung RT, Ludwig DA; PEDS-C Clinical Research Network. Correlates of adiponectin in hepatitis C-infected children: the importance of body mass index. J Pediatr Gastroenterol Nutr. 2015 Feb;60(2):165-70. doi: 10.1097/MPG.0000000000000604.

  PMID: 25313851 RESULT

• Schwarz KB, Molleston JP, Jonas MM, Wen J, Murray KF, Rosenthal P, Gonzalez-Peralta RP, Lobritto SJ, Mogul D, Pavlovic V, Warne C, Wat C, Thompson B. Durability of Response in Children Treated With Pegylated Interferon alfa [corrected] 2a +/- Ribavirin for Chronic Hepatitis C. J Pediatr Gastroenterol Nutr. 2016 Jan;62(1):93-6. doi: 10.1097/MPG.0000000000000929.

  PMID: 26284539 RESULT

• Molleston JP, Mellman W, Narkewicz MR, Balistreri WF, Gonzalez-Peralta RP, Jonas MM, Lobritto SJ, Mohan P, Murray KF, Njoku D, Rosenthal P, Barton BA, Talor MV, Cheng I, Schwarz KB, Haber BA; PEDS-C Clinical Research Network. Autoantibodies and autoimmune disease during treatment of children with chronic hepatitis C. J Pediatr Gastroenterol Nutr. 2013 Mar;56(3):304-10. doi: 10.1097/MPG.0b013e3182774cae.

  PMID: 23439301 DERIVED

• Jonas MM, Balistreri W, Gonzalez-Peralta RP, Haber B, Lobritto S, Mohan P, Molleston JP, Murray KF, Narkewicz MR, Rosenthal P, Schwarz KB, Barton BA, Shepherd JA, Mitchell PD, Duggan C. Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial. Hepatology. 2012 Aug;56(2):523-31. doi: 10.1002/hep.25690. Epub 2012 Jul 6.

  PMID: 22383118 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis; Hepatitis C

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Kathleen B. Schwarz, M.D.
• Organization: Johns Hopkins University School of Medicine

kschwarz@jhmi.edu

410-955-8769

Study Officials

• Kathleen B Schwarz, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2005
• First Posted: January 5, 2005
• Study Start: December 1, 2004
• Primary Completion: August 1, 2008
• Study Completion: February 1, 2010
• Last Updated: October 24, 2018
• Results First Posted: July 1, 2013

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data were posted to the NIDDK Central Repository in March 2013.
• Access Criteria: Data can be requested from the NIDDK Central Repository. A signed data use agreement is required.

Locations

US (11)