Chronic Hepatitis C
Conditions
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
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.
Interventions
DRUGPegylated Interferon/ribavirin
Sponsors
Roche Pharma AG
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Viral Response (SVR) | at least 24 weeks after stopping treatment. | SVR is defined as nondetectable hepatitis C virus ribonucleic acid (HCV RNA) in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | At any time up to 72 weeks | Influenza-like, headache, and gastrointestinal symptoms |
Countries
United States
Participant flow
Recruitment details
December 2004 to May 2006 at 11 US medical centers
Pre-assignment details
Failure to meet inclusion criteria
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon/Ribavirin 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. | 55 |
| Pegylated Interferon/Placebo 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). | 59 |
| Total | 114 |
Baseline characteristics
| Characteristic | Pegylated Interferon/Placebo | Pegylated Interferon/Ribavirin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 59 Participants | 55 Participants | 114 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.8 years STANDARD_DEVIATION 3.6 | 10.7 years STANDARD_DEVIATION 3.3 | 10.75 years STANDARD_DEVIATION 3.4 |
| Region of Enrollment United States | 59 participants | 55 participants | 114 participants |
| Sex: Female, Male Female | 23 Participants | 28 Participants | 51 Participants |
| Sex: Female, Male Male | 36 Participants | 27 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / 55 | 52 / 59 |
| serious Total, serious adverse events | 2 / 55 | 1 / 59 |
Outcome results
Primary
Sustained Viral Response (SVR)
SVR is defined as nondetectable hepatitis C virus ribonucleic acid (HCV RNA) in plasma
Time frame: at least 24 weeks after stopping treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG/RV | Sustained Viral Response (SVR) | 29 participants |
| PEG/Placebo | Sustained Viral Response (SVR) | 12 participants |
Secondary
Adverse Events
Influenza-like, headache, and gastrointestinal symptoms
Time frame: At any time up to 72 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PEG/RV | Adverse Events | Influenza-like symptoms | 50 Participants |
| PEG/RV | Adverse Events | Headache | 34 Participants |
| PEG/RV | Adverse Events | Gastrointestinal symptoms | 31 Participants |
| PEG/Placebo | Adverse Events | Influenza-like symptoms | 50 Participants |
| PEG/Placebo | Adverse Events | Headache | 30 Participants |
| PEG/Placebo | Adverse Events | Gastrointestinal symptoms | 37 Participants |