Hansenula-Derived Pegylated-Interferon Alpha-2a in Egyptian Children With Chronic HCV

Hepatitis C, Chronic Clinical Trial

Official title:

Safety and Efficacy of Hansenula-Derived Pegylated-Interferon Alpha-2a and Ribavirin Customized Combination Therapy in Egyptian Children With Chronic Hepatitis C Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02027493
• Other study ID #: NLI-YAGCC-CUPH-HCV-PEG-PED
• Status: Completed
• Phase: N/A
• First received: January 1, 2014
• Last updated: January 3, 2014
• Start date: February 2009
• Est. completion date: August 2011

Study information

• Verified date: January 2014
• Source: National Liver Institute, Egypt
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Egypt has the highest prevalence of hepatitis C virus infection in adults (up to 20%) and children (up to 5.5%). The major genotype (90%) is type 4. Pegylated interferon-alpha-2a or -2b and ribavirin have been used in small numbers of hepatitis C virus-infected children with sustained virological response being higher in genotypes 2 and 3 than in genotypes 1 and 4. Genotype 4 is has been described as difficult-to-treat genotype. Several attempts to modify treatment protocols have been tried in adults in an attempt to achieve higher rates of sustained virological response. Shortening injection interval and/or treatment duration prolongation have been tried with variable outcome reports.

A novel Hansenula- derived pegylated interferon alpha 2a: 20 Kilo dalton (Reiferon Retard) has been used over the last 4 years in the Egyptian market.

We aimed to investigate the safety and efficacy of Reiferon retard plus ribavirin customized regimen in hepatitis C virus-RNA seropositive Egyptian children. Forty six children with chronic hepatitis C virus aged 3-19 years were selected from 3 hepatic tertiary centers.

Clinical and laboratory evaluation were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was done before starting treatment, at 4, 12, 24, 48, 72 weeks during treatment and 6 months after stoppage of treatment. All patients were assigned to receive a weekly subcutaneous injection of pegylated interferon alpha 2-a ( Reiferon Retard) plus oral Ribavirin daily for 12 weeks ,then cases were divided according to PCR results into 2 groups.

Group I: Patients who continued treatment on weekly basis: this group included patients who had negative PCR at week 12 as well those who had positive PCR without any change in viremia. Group II: Patients who continued treatment on a 5- days schedule: this group included patients who had any decrease in viremia at week 12.

Patients who were PCR-negative at week 48 and had at least one PCR-positive test during therapy were assigned to have an extended treatment course of 6 months duration.

The occurrence of adverse effects was assessed during treatment and follow up

Description:

hepatitis C virus is a major health problem, not only in adults but also in the pediatric age group. In Egypt, the prevalent genotype is the difficult-to-treat genotype 4. Attempts are being made to improve the treatment outcomes. In the current study we aim to investigate the effect of customized pegylated interferon-alpha-2a plus ribavirin in children with chronic hepatitis C virus. For that, 46 children with chronic hepatitis C virus were recruited from three tertiary Pediatric Hepatology centers. All were assigned to receive weekly subcutaneous pegylated interferon-alpha-2a plus daily ribavirin for 12 weeks. At this point, the study population was divided into two arms. Arm 1 included those who became hepatitis C virus-RNA negative by polymerase chain reaction and those who showed no change of viremia or a decrease of less than 1 log. This group continued treatment on weekly bases for 48 weeks, even those who are hepatitis C virus-RNA positive. Arm 2; included patients who had a decrease in viremia more than one log of pre-treatment viremia level. For those patients, injection interval was shortened to every 5-day for a completion period of 48 weeks. Patients from either group who were polymerase chain reaction-negative at week 48, but had at least one polymerase chain reaction-positive test during therapy, were assigned to have an extended treatment course up to 72 weeks.

So the first customization was,

1. prolongation of treatment duration for up to 48 weeks regardless response type

2. Shortening injection interval in some patients to every 5-day injection

3. The third customization was the prolongation of treatment for extra 6 months, i.e. up tp 72 weeks in some patients.

The occurrence of adverse effects, virological and biochemical responses were assessed during treatment and follow up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: August 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 19 Years

Eligibility

Inclusion Criteria:

• children aged 3-19 years

• compensated chronic HCV infection (HCV-RNA positive by PCR for more than 6 months)

• whose hemoglobin was =10 g/dL

• neutrophilic count > 1500/mm3

• platelet count > 75,000/mm3

• normal random blood sugar

• normal serum creatinine

• normal serum ferritin

• normal thyroid function tests

• normal lipid profile

• no other causes of liver disease (autoimmune hepatitis, Wilson disease, alpha one antitrypsin deficiency nor hepatitis B virus infection).

• Liver biopsy was mandatory for enrollment

Exclusion Criteria:

• decompensated cirrhosis

• any other cause of liver disease associating HCV infection

• body mass index = 95 percentile

• severe psychiatric conditions

• uncontrolled seizure disorder

• decompensated cardiovascular disease, renal insufficiency

• evidence of retinopathy

• decompensated thyroid disease

• hemoglobinopathy

• immunologically mediated diseases or any other chronic illness requiring long term immunosuppressive drugs

• previous interferon therapy within one year of enrollment

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Reiferon R
subcutaneous injection of 100 µg/m2
• Ribavirin
15 mg/kg daily on two divided doses

Locations

Country	Name	City	State
Egypt	Department of Pediatrics, Cairo University Pediatric Hospital	Cairo
Egypt	Yassin Abdel Ghaffar Charity Center for Liver Disease and Research	Cairo
Egypt	National Liver Institute	Menoufiya	Menofiya

Sponsors (5)

Lead Sponsor	Collaborator
National Liver Institute, Egypt	Ain Shams University, Cairo University, National Hepatology & Tropical Medicine Research Institute, Yassin Abdel Ghaffar Charity Center for Liver Disease and Research, Cairo, Egypt

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess predictors of sustained virological response	compare demographic parameters in responders and non-responders; comparing pretreatment hepatitis C viremia in responders and non-responders; compare expected duration of infection in responders and non-responders; compare histopathological changes in responders and non-responders; compare pretreatment liver enzymes in responders and non-responders; compare treatment duration in responders and non-responders; compare injection interval in responders and non-responders	96 weeks	No
Primary	To study the safety of Hansenula-Derived Pegylated-Interferon Alpha-2a (Reiferon retard) in attaining sustained virological response in children with chronic hepatitis C virus infection	The efficacy and Safety was assessed during the 48 weeks of therapy, patients were monitored clinically, laboratory for the appearance of any side effects	48 weeks	Yes
Secondary	Efficacy of treatment customization on the outcome	To assess the effect of tailoring treatment [by decreasing the interval between injection (5days vs 7 days) and prolonging duration of therapy (48 weeks vs 72 weeks)] on sustained virological response based on the on-treatment virologic response	96 weeks	Yes