Chronic Hepatitis B Clinical Trial
Official title:
Efficacy of HBV Therapeutic Vaccine in Consolidation of Nucleos(t)Ide Analogues Therapy: a Pilot Study
Verified date | December 2018 |
Source | Chang Gung Memorial Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 116 |
Est. completion date | December 21, 2018 |
Est. primary completion date | December 21, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 31 Years to 76 Years |
Eligibility |
Inclusion Criteria: 1. HBeAg negative chronic hepatitis B 2. Has been receiving a 3-year or more than 3 years entecavir or tenofovir therapy and intending to stop the treatment 6 months later. 3. An inform consent will be obtained after well explanation. Exclusion Criteria: 1. Pregnant woman. 2. Hepatitis C virus, hepatitis D virus or human immunodeficient virus co-infection. 3. Alcoholism 4. Present with malignant tumor, decompensated liver or renal diseases, present with other major medical illness. 5. Liver cirrhosis, child B or C. |
Country | Name | City | State |
---|---|---|---|
Taiwan | Chang Gung Memorial Hospital | Taipei |
Lead Sponsor | Collaborator |
---|---|
Chang Gung Memorial Hospital |
Taiwan,
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* Note: There are 60 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | HBV DNA levels during followup period | 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. 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. 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 | |
Primary | HBV DNA levels during followup period | 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. 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. 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 | Alanine aminotransferase (ALT) level during followup period | ALT level after completed therapy will be grouped into normal serum ALT level, 1-2x upper limit normal (ULN), 2-5x ULN or >5x ULN. ALT relapse is defined as ALT level >2x ULN. | At 48 th week of followup after completed combination therapy | |
Secondary | Alanine aminotransferase (ALT) level during followup period | ALT level after completed therapy will be grouped into normal serum ALT level, 1-2x upper limit normal (ULN), 2-5x ULN or >5x ULN. ALT relapse is defined as ALT level >2x ULN. | At 96th weeks of followup after completed combination therapy | |
Secondary | Quantitative HBsAg (qHBsAg) level during followup period | Serum qHBsAg level after completed therapy will be grouped into lower than 150 international unit (IU)/mL, 500 IU/mL, 500-1000 IU/mL and >1000 IU/mL. Those qHBsAg lower than 150 IU/mL is defined as good serological response. | At 48th week of followup after completed combination therapy | |
Secondary | Quantitative HBsAg (qHBsAg) level during followup period | Serum qHBsAg level after completed therapy will be grouped into lower than 150 international unit (IU)/mL, 500 IU/mL, 500-1000 IU/mL and >1000 IU/mL. Those qHBsAg lower than 150 IU/mL is defined as good serological response. | At 96th week of followup after completed combination therapy |
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