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

NCT ID: NCT02982837

Last Updated: 2018-03-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2019-05-31

Brief Summary

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).

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.

Conditions

Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PEG-IFN & NUCLEOTIDE ANALOGUES

Peginterferon alfa-2a 180 Mcg infusion per week with ongoing NUCLEOTIDE ANALOGUES for 48 weeks.

Group Type: EXPERIMENTAL

PEG-IFN & Nucleos(t)tide analogues

Intervention Type: DRUG

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.

Nucleos(t)tide analogues

Intervention Type: DRUG

Subjects will continue on the same dose of Nucleoside/nucleotide analogues as they started the study.

NUCLEOTIDE ANALOGUES

Nucleoside same dose as they started the study.

Group Type: ACTIVE_COMPARATOR

Nucleos(t)tide analogues

Intervention Type: DRUG

Subjects will continue on the same dose of Nucleoside/nucleotide analogues as they started the study.

Interventions

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.

Intervention Type: DRUG

Nucleos(t)tide analogues

Subjects will continue on the same dose of Nucleoside/nucleotide analogues as they started the study.

Intervention Type: DRUG

Other Intervention Names

Immunomodulatory therapy; Nucleoside/nucleotide analogues

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

King Abdullah International Medical Research Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abduljaleel Alalwan, MD

Role: PRINCIPAL_INVESTIGATOR

National Guards Health Affairs-Riyadh

Locations

King Abdulaziz Medical City

Jeddah, , Saudi Arabia

Site Status: RECRUITING

King Abdulaziz Hospital

Jeddah, , Saudi Arabia

Site Status: RECRUITING

King Abdulaziz Medical City

Riyadh, , Saudi Arabia

Site Status: RECRUITING

Countries

Saudi Arabia

Central Contacts

Abduljaleel Alalwan, MD

Role: CONTACT

alwana@ngha.med.sa

801 111 ext. 11622

Ansif Majeed, MBA

Role: CONTACT

pallathmajeedan@ngha.med.sa

(011)429-9999 ext. 94436

Facility Contacts

Faisal Sanai, MD

Role: primary

sanaifa@ngha.med.sa

+966 12 2266666 ext. 24828

Elsadig Ahmed Nour Mohamed, MD

Role: primary

mohamedel1@ngha.med.sa

Abduljaleel Alwan, MD

Role: primary

alwana@ngha.med.sa

801 111 ext. 11622

Ansif Majeed, MBA

Role: backup

pallathmajeedan@ngha.med.sa

(011)429-9999 ext. 94436

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Other Identifiers

PDU15001

Identifier Type: -

Identifier Source: org_study_id