To Study the Effect of Adding on Pegylated Interferon (PEG-INF) Therapy for Patients Diagnosed With Chronic Hepatitis B (RC14/055)

March 8, 2018 updated by: King Abdullah International Medical Research Center

Randomized, Multicenter, Open -Label Clinical Trial to Study the Effect of Adding on Pegylated Interferon Therapy for Patients Diagnosed With Chronic Hepatitis B Showing Maintained Response While Receiving Ongoing Nucleotide Analogues

To assess whether PEG-INF (Peglyated - interferon) Add-on therapy in patients of CHB who have achieved a maintained viral suppression (HBV DNA PCR( polymerase chain reaction) <200 for last 3-6 month) with NA's can result in increased rate of HBV infection eradication (HbsAg is undetectable by serological blood testing with or without seroconversion to HBs antibody).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hepatitis B virus (HBV) infection remains a global health care problem with more than one third of world's population having serological evidence of been exposed to the virus and about 5% of global population ( 350-400 million) being chronically infected. About 15-40% of Patients with chronic hepatitis B (CHB) infection develop complications of liver cirrhosis, liver failure and hepatocellular carcinoma(HCC) in their life time , resulting in an estimated of 500,000 to 1.2 million deaths each year. In Saudi Arabia, chronic hepatitis B remains a serious medical problem, despite the implementation of mandatory HBV vaccination of children since 1989. According to a recent study conducted in Saudi hospital, HBV accounts for 49% of the hepatitis cases . Persistent viral replication is associated with disease progression to liver fibrosis, cirrhosis and development of HCC. Currently two classes of drugs are available for treatment of CHB namely immunomodulatory therapy (conventional & pegylated interferon (Pegasys) PEG-IFN) and nucleoside/nucleotide analogues(NA). Interferon(IFN)-α with its dual immunomodulatory and antiviral effects was the first drug (recombinant standard IFN- α) licensed for Chronic hepatitis B treatment in the 1990's followed by introduction of nucleos(t)ide analogues(NA) in 1998 that directly inhibit HBV polymerase and provide an effective on treatment maintained viral suppression . With the introduction of pegylated interferon- α (PEG-IFN) in 2005 that allows a convenient once a week dosing interval and of equal or superior treatment efficacy than conventional (IFN), the interferon based therapy has markedly improved its utility. Due to its predominant immunomodulatory effect peginterferon (PEG-IFN) offers the advantage of higher sustained off treatment response rate compared to NA thus allowing a finite duration of treatment. The NA act by directly inhibiting HBV polymerase resulting in effective on treatment maintained viral suppression (HBV DNA PCR <200 for last 3-6 month)). However, long term NA therapy has the problems of emergence of viral resistance, long -term safety, cost and patient compliance.

Study Type

Interventional

Enrollment (Anticipated)

214

Phase

  • Phase 4

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Saudi Arabia
      • Jeddah, Saudi Arabia, 22384
        • Recruiting
        • King Abdulaziz Medical City
        • Contact:
      • Jeddah, Saudi Arabia, 31982
      • Riyadh, Saudi Arabia, 11426

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

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adults ≥18 & < 70 years of both genders.
  • CHB on NA's in maintained viral suppression (HBV DNA PCR <200 for last 3-6 month)
  • Patients with measurable HBsAg quantitative levels
  • Patients with any HBV genotypes.
  • Patients with either CHB e Ag positive or eAg negative
  • Patients who sign an informed consent for inclusion into the study.
  • Patients with hepatitis Delta co-infection.
  • only patients with a negative pregnancy test who are of child bearing potential and agree to utilize a strict birth control method will be enrolled

Exclusion Criteria:

  • Patients with following characteristics will not be considered for the trial:
  • Decompensated liver Cirrhosis
  • HCV (hepatitis C virus) or HIV co infection.
  • Autoimmune disorders like SLE (Systemic lupus erythematosus), RA (Rheumatoid Arthritis ), AIH (Autoimmune Hemolytic Anemia), ITP (Immune thrombocytopenic purpura), psoriasis etc.
  • Untreated psychiatric conditions like depression and alcohol or drug abuse.
  • Comorbid conditions like chronic renal failure or post renal/liver transplantation on immunosuppressive therapy.
  • Complicated diabetes mellitus and advanced heart failure.
  • Pregnancy or not willing to practice contraception.
  • Known allergy to Interferons.
  • Concomitant treatment with Telbivudine
  • Evidence of portal hypertension by Biochemical (Low Platelets less than 100), imaging or UGI (upper gastrointestinal)endoscopy

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PEG-IFN & NUCLEOTIDE ANALOGUES
Peginterferon alfa-2a 180 Mcg infusion per week with ongoing NUCLEOTIDE ANALOGUES for 48 weeks.
Drug: PEG-IFN & Nucleos(t)tide analogues
Subjects who will be randomized to receive 180 Mcg/ week as an add-on Pegylated Interferon therapy α-2 A with their ongoing NUCLEOTIDE analogues for 48 weeks.
Other Names:
  • Immunomodulatory therapy
Drug: Nucleos(t)tide analogues
Subjects will continue on the same dose of Nucleoside/nucleotide analogues as they started the study.
Other Names:
  • Nucleoside/nucleotide analogues
Active Comparator: NUCLEOTIDE ANALOGUES
Nucleoside same dose as they started the study.
Drug: Nucleos(t)tide analogues
Subjects will continue on the same dose of Nucleoside/nucleotide analogues as they started the study.
Other Names:
  • Nucleoside/nucleotide analogues

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The loss of HbsAg between groups (NA) group and NA +Peg_INF group assessed by HbsAg test
Time Frame: 48 weeks
The loss of HbsAg between groups (NA) group and NA +Peg_INF group assessed by HbsAg test
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The seroconversion to HBs antibody between groups (NA) group and NA +Peg_INF group assessed by Hbe Ab test
Time Frame: 6 ,12 months & 48 weeks
The seroconversion to HBs antibody between groups (NA) group and NA +Peg_INF group assessed by Hbe Ab test
6 ,12 months & 48 weeks
The HBeAg (Hepatitis B e-Antigen) loss in CHRONIC HBV eAg positive patient between groups (NA) group and NA +Peg_INF group assessed by HbeAg test
Time Frame: 6,12 months & 48 weeks
HBeAg loss in CHRONIC HBV eAg positive patient between groups (NA) group and NA +Peg_INF group assessed by HbeAg test
6,12 months & 48 weeks
The conversion of HBeAg to HBe-antibody in CHRONIC HBV eAg (eAntigen) positive patient between groups (NA) group and NA +Peg_INF group assessed by HBe-antibody test
Time Frame: 6,12 months & 48 weeks
The conversion of HBeAg to HBe-antibody in CHRONIC HBV eAg positive patient between groups (NA) group and NA +Peg_INF group assessed by HBe-antibody test
6,12 months & 48 weeks
The correlation between HBsAg ( Hepatitis B Surface Antigen) levels while on therapy at the a defined interval ie 8,12.24,36,48 weeks and rate of HBsAg loss at end of therapy assessed by measuring HBV s Ag during the period 8,12.24,36 and 48 weeks
Time Frame: 8,12,24 and 48 weeks
The correlation between HBsAg levels while on therapy at the a defined interval ie 8,12.24,36,48 weeks and rate of HBsAg loss at end of therapy assessed by measuring HBV s Ag during that period 8,12.24,36 and 48 weeks
8,12,24 and 48 weeks
The relationship between HBV genotype and HBsAg loss at the end of the study assessed by measuring HBV genotype only at base line and see if any particular genotype have more HBV sAg loss at the end of the study
Time Frame: At base line & 48 weeks
The relationship between HBV genotype and HBsAg loss at the end of the study assessed by measuring HBV genotype only at base line and see if any particular genotype have more HBV sAg loss at the end of the study
At base line & 48 weeks
The relationship between IL28B (Interleukin 28B) genotypes ( polymorphism) and HBsAg loss with or without seroconversion to HBs antibody
Time Frame: At base line & 48 weeks
The relationship between IL28B genotypes ( polymorphism) and HBsAg loss with or without seroconversion to HBs antibody assess by doing IL28B genotypes ( polymorphism) once during the study and see if any specific IL28B genotypes ( polymorphism) associated more with HBV sAg loss at the end of the study with or without seroconversion to HBs antibody).
At base line & 48 weeks
The relationship between vitamin D deficiency and (HbsAg loss with or without seroconversion to HBs antibody) assess by measuring Vitamin D level at base line And correlate the baseline level of Vitamin with HBV sAg loss at the end of the study
Time Frame: At base line & 48 weeks
The relationship between vitamin D deficiency and (HbsAg loss with or without seroconversion to HBs antibody) assess by measuring vitamin D level at base line And correlate the base line level of vitamin D with HBV sAg loss at the end of the study
At base line & 48 weeks

Collaborators and Investigators

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

Sponsor

King Abdullah International Medical Research Center

Collaborators

Hoffmann-La Roche

Investigators

  • Principal Investigator: Abduljaleel Alalwan, MD, National Guards Health Affairs-Riyadh

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2015

Primary Completion (Anticipated)

March 1, 2019

Study Completion (Anticipated)

May 1, 2019

Study Registration Dates

First Submitted

August 7, 2016

First Submitted That Met QC Criteria

December 1, 2016

First Posted (Estimate)

December 6, 2016

Study Record Updates

Last Update Posted (Actual)

March 9, 2018

Last Update Submitted That Met QC Criteria

March 8, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PDU15001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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