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

January 3, 2014 updated by: Mostafa M. Sira, National Liver Institute, Egypt

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
46

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt, 2851
        • Yassin Abdel Ghaffar Charity Center for Liver Disease and Research
      • Cairo, Egypt
        • Department of Pediatrics, Cairo University Pediatric Hospital
    • Menofiya
      • Menoufiya, Menofiya, Egypt, 32511
        • National Liver Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 years to 19 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Reiferon R weekly plus ribavirin
patients who continued treatment on weekly basis (7-day schedule). This group included patients who were HCV-RNA negative at week 12 and those who had < 1 log decrease in HCV-RNA viremia
Drug: Reiferon R
subcutaneous injection of 100 μg/m2
Other Names:
  • Hansenula-derived pegylated interferon alpha 2a
  • Reiferon Retard
Drug: Ribavirin
15 mg/kg daily on two divided doses
Active Comparator: Reiferon R (every 5-day) plus ribavirin
patients who continued treatment on a 5-day schedule. This group included patients who had ≥ 1 log decrease in viremia (compared to pre-treatment level) at week 12
Drug: Reiferon R
subcutaneous injection of 100 μg/m2
Other Names:
  • Hansenula-derived pegylated interferon alpha 2a
  • Reiferon Retard
Drug: Ribavirin
15 mg/kg daily on two divided doses

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: 48 weeks
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Efficacy of treatment customization on the outcome
Time Frame: 96 weeks
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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To assess predictors of sustained virological response
Time Frame: 96 weeks
  1. compare demographic parameters in responders and non-responders
  2. comparing pretreatment hepatitis C viremia in responders and non-responders
  3. compare expected duration of infection in responders and non-responders
  4. compare histopathological changes in responders and non-responders
  5. compare pretreatment liver enzymes in responders and non-responders
  6. compare treatment duration in responders and non-responders
  7. compare injection interval in responders and non-responders
96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Liver Institute, Egypt

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Cairo University
Ain Shams University
Yassin Abdelghaffar Charity Center for Liver Disease and Research
National Hepatology & Tropical Medicine Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Mostafa M Sira, M.D., Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
  • Principal Investigator: Tawhida Y Abdel-Ghaffar, M.D., Yassin Abdel Ghaffar Charity Center for Liver Disease and Research, 2851 Cairo, Egypt
  • Study Director: Suzan El Naghi, M.D., Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 11441 Cairo, Egypt
  • Study Chair: Hanaa El-Karaksy, M.D., Cairo University
  • Study Chair: Heba Helmy, M.D., Cairo University
  • Study Chair: Mona S El-Raziky, M.D., Cairo University
  • Study Chair: Elham F Abdel-Aty, M.Sc., Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
  • Study Chair: Aleef A Allam, M.D., Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
  • Study Chair: Hanaa A El-Araby, M.D., Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
  • Study Chair: Behairy E Behairy, M.D., Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
  • Study Chair: Mohamed A El Guindi, M.D.; Ph.D., Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
  • Study Chair: Hatem El-Sebaie, M.D., Biochemistry Department, National Liver Institute, 32511 Menofiya, Egypt
  • Study Chair: Aisha Y Abdel-Ghaffar, M.D., Clinical Pathology Department, Ain Shams University, Cairo, Egypt
  • Study Chair: Nermin A Ehsan, M.D., Pathology Department, National Liver Institute, Menofiya University, Shebin El-koom, 32511 Menofiya, Egypt
  • Study Chair: Ahmad El-Hennawy, M.D., Pathology Department, Cairo University, Faculty of Medicine, Kasr El-Aini, Cairo, Egypt

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

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Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 1, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 6, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 6, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2014

More Information

Terms related to this study

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Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NLI-YAGCC-CUPH-HCV-PEG-PED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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