Efficacy of HBV Vaccine in Consolidation of Nucleos(t)Ide Analogues Therapy

NCT02505009 | Completed Phase 4 DMC

• 1 other identifier: 104-3167C
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

Background and aims: Nucleos(t)ide analogues may suppress HBV DNA to undetectable level, but only about 30-40% remain sustained response 1-3 years after discontinued therapy. The investigators will try to improve the sustained response rate by given a course of HBV vaccination during the last 6 months on patients receiving a 3-year entecavir or tenofovir therapy. Rational: The host may response to HBV vaccine when HBV DNA and immune tolerance are suppressed during entecavir or tenofovir therapy. Patients: Patients who have been receiving entecavir or tenofovir therapy for at least 30 months will be invited to this study. The case group will receive 5 Engerix-B injections during the last 6 months of entecavir or tenofovir therapy. Arm A-entecavir pretreated group: 75 cases will be enrolled to receive Engerix-B injection and compared with histological non-vaccine treated controls; Arm B-tenofovir pretreated group: 50 patients will be randomized into case (vaccine) and control group according to age, gender, pretreatment HBV DNA level. Therapy: Both case and control groups will receive a 3 year or longer entecavir or tenofovir therapy. Patients will be screen at 24-30 months and enrolled at 30 months after entecavir or tenofovir therapy. They will receive 5 Engerix-B injections at 0,1st ,2nd,3rd and 6th month \[30-36 +/-1 month post nucleos(t)ide therapy\] post enrollment. Both drugs will be discontinued after completed therapy. Follow-up: Both groups will be monitoring by biochemistry, alpha-fetoprotein, quantitative HBsAg, HBV DNA levels and immunological parameter periodically for 2 years after therapy. Efficacy: Those patients with persistent normal ALT and HBV DNA lower than 1\*100000 cps/mL after discontinued nucleos(t)ide analogues therapy will be considered to have sustained response. Patients with transient elevation of HBV DNA and ALT, but normalized spontaneously without further therapy will be defined as delayed response. Patients with persistent HBV DNA greater than 1\*100000 cps/mL will be considered to have non-sustained response. Study duration: The enrollment will be completed in one year and keep on observation for additional 2 years. Expected goals of the study: HBV vaccine and nucleos(t)ide analogues combination therapy may decrease the HBV relapse rate at 1 and 2 year after completed therapy.

Conditions

Chronic Hepatitis B

Keywords

Therapeutic Uses; Entecavir; Tenofovir; Engerix-B; DNA Virus Infections; Antiviral Agents; Vaccination

Outcome Measures

Primary Outcomes (2)

• HBV DNA levels during followup period

  1. Non-responder: When HBV DNA levels were greater than 1\*100000 cps/mL and persistence to 1 year after stopped combination therapy, or need other therapy before the end point. 2. Delayed responder: Those patients with transient elevation of HBV DNA shortly after stopped NA therapy and then become normal ALT and HBV DNA lower than 1\*100000 cps/mL without other therapy. 3. Sustained responder:HBV DNA levels were lower than 1\*100000 cps/mL and persistence to 1 year after stopped combination therapy

  At 48th weeks of followup after completed combination therapy

• HBV DNA levels during followup period

  1. Non-responder: When HBV DNA levels were greater than 1\*100000 cps/mL and persistence to 2 years after stopped combination therapy, or need other therapy before the end point. 2. Delayed responder: Those patients with transient elevation of HBV DNA shortly after stopped NA therapy and then become normal ALT and HBV DNA lower than 1\*100000 cps/mL without other therapy. 3. Sustained responder:HBV DNA levels were lower than 1\*100000 cps/mL and persistence to 2 years after stopped combination therapy

  At 96th weeks of followup after completed combination therapy

Secondary Outcomes (4)

• Alanine aminotransferase (ALT) level during followup period

  At 48 th week of followup after completed combination therapy

• Alanine aminotransferase (ALT) level during followup period

  At 96th weeks of followup after completed combination therapy

• Quantitative HBsAg (qHBsAg) level during followup period

  At 48th week of followup after completed combination therapy

• Quantitative HBsAg (qHBsAg) level during followup period

  At 96th week of followup after completed combination therapy

Study Arms (4)

entecavir pretreated vaccine arm

EXPERIMENTAL

Arm A,case group: 75 cases will be enrolled to receive Engerix-B injection and compared with histological non-vaccine treated controls

Drug: Engerix-B; Drug: Entecavir

tenofovir pretreated vaccine arm

EXPERIMENTAL

Arm B case group: A total of 50 patients will be randomized into case (vaccine) and control group according to age, gender, pretreatment HBV DNA level.

Drug: Engerix-B; Drug: Tenofovir

Entecavir pretreated control arm

ACTIVE COMPARATOR

Arm A control group: Age, gender and pretreatment DNA matched histological controls

Drug: Entecavir

tenofovir pretreated control arm

ACTIVE COMPARATOR

Arm B control group: A total of 50 patients will be randomized into case (vaccine) and control group according to age, gender, pretreatment HBV DNA level.

Drug: Tenofovir

Interventions

Engerix-B DRUG

The case group will receive 5 Engerix-B injections during the last 6 months of a 3-year NA therapy.

entecavir pretreated vaccine arm; tenofovir pretreated vaccine arm

Tenofovir DRUG

Both case and control will receive 300 mg Tenofovir for at least 3 years

tenofovir pretreated control arm; tenofovir pretreated vaccine arm

Entecavir DRUG

Both case and control will receive 0.5 mg entecavir therapy for at least 3 years

Entecavir pretreated control arm; entecavir pretreated vaccine arm

Eligibility Criteria

• Age: 31 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HBeAg negative chronic hepatitis B
• Has been receiving a 3-year or more than 3 years entecavir or tenofovir therapy and intending to stop the treatment 6 months later.
• An inform consent will be obtained after well explanation.

You may not qualify if:

• Pregnant woman.
• Hepatitis C virus, hepatitis D virus or human immunodeficient virus co-infection.
• Alcoholism
• Present with malignant tumor, decompensated liver or renal diseases, present with other major medical illness.
• Liver cirrhosis, child B or C.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital

Taipei, 10507, Taiwan

Location

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MeSH Terms

Conditions

Hepatitis B, Chronic; DNA Virus Infections

Interventions

Engerix-B; Tenofovir; entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Dar-In Tai, MD, PhD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 22, 2015
• Study Start: May 1, 2015
• Primary Completion: December 21, 2018
• Study Completion: December 21, 2018
• Last Updated: July 30, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)