Clinical trial NCT00100659: PEDS-C: Pegylated Interferon +/- Ribavirin for Children With Hepatitis C
Official title: Pegylated Interferon +/- Ribavirin for Children With Hepatitis C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: Roche Pharma AG
First posted: 2005-01-05
Enrollment: 114
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Evidence of severe retinopathy
* Coagulopathy (international normalized ratio\>1.5)
* Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is \>20% within 2 years.
* Hemoglobinopathy
* Hemophilia
* Severe retinopathy
* History of other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
* Sexually active females of child-bearing potential (defined as age 10 years and older) and sexually active men who are not practicing two forms of effective contraception during treatment and during the 6 months after treatment has been concluded
* Females who have a positive serum pregnancy test within 7 days of initiation of treatment or who are breast-feeding
* Males whose female partners are pregnant
* Active substance abuse
* A sibling and/or any other child living in the same household or sharing the same primary caregiver enrolled in the study.

Primary outcomes:
measure: Sustained Viral Response (SVR)
timeFrame: at least 24 weeks after stopping treatment.
Secondary outcomes:
measure: Adverse Events
timeFrame: At any time up to 72 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: The Children's Hospital
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana University School of Medicine, James Whitcomb Riley Hospital for Children
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center
state: Washington
Study officials:
affiliation: Johns Hopkins University
name: Kathleen B Schwarz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.