Efficacy of HBVaxpro40© and Fendrix© in Patients With Chronic Liver Disease.

NCT ID: NCT03459521

Last Updated: 2022-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-01
• Study Completion Date: 2021-08-01

Brief Summary

Background: Cirrhotic patients have an increased risk of infections. In these patients is important to prevent hepatitis B virus (HBV) infection, as it may cause a deterioration of liver function. However, HBV vaccine efficacy in this group of patients is lower than in healthy population. Despite increasing standard doses to double doses or administering an accelerated pattern, the response to HBV vaccination remains suboptimal. For this reason, an alternative strategy may be using vaccines with novel adjuvants such as Fendrix® or the recombinant vaccine HBVAXPRO®.

Aim: To assess the adjuvanted HBV vaccine (Fendrix ®) efficacy in patients with chronic liver disease and to understand the kinetics of anti-HBs titers over time in patients who respond to vaccination.

Methods: Prospective and multicenter study. Serological markers of HBV will be assessed prospectively in consecutive patients with non-cirrhotic liver disease (permanent abnormal liver blood tests > six months; elastogram ≥8 kilopascal (kPa); serum markers of fibrosis (APRI or FIB-4 ≥ F2); ultrasound changes suggesting chronic liver disease) and cirrhotic patients (diagnosed by liver biopsy and/or non-invasive methods: clinical, blood tests and ultrasound). Seronegative patients will receive four doses of Fendrix ® at 0,1, 2 and 6 months. Antibodies against HBV superficial antigen (anti-HBs) will be determined at 2 months +/- 10 days, six months and one year after having received the fourth dose of the vaccine (to see kinetics). The study will differentiate between responders and non-responders to the vaccine: adequate immunity to HBV will be defined as anti-HBs higher than > 10mUI/mL (standard definition of seroconversion) and> 100mUI/mL. Investigators will evaluate the factors that influence the response, kinetics and safety of the vaccination in patients with chronic liver disease and cirrhosis.

Detailed Description

Intervention: Serological markers of HBV will be assessed prospectively in consecutive non-cirrhotic liver disease or cirrhotic patients. Seronegative patients willing to participate will sign a written informed consent and will receive four doses of 20 µg Fendrix ® at 0,1, 2 and 6 months or HBVAXPRO® at 0,1 and 6 months, depending on availability. Antibodies against HBV superficial antigen (anti-HBs) will be determined at 2 months +/- 10 days, six and twelve months after having received the fourth dose of the vaccine (to see kinetics). The study will differentiate between responders and nonresponders to the vaccine: adequate immunity to HBV will be defined as anti-HBs higher than > 10mUI/mL (standard definition of seroconversion) and > 100mUI/mL. Adverse events will be assessed throughout the treatment period.

Conditions

Liver Disease Chronic; Hepatitis B Virus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Fendrix HBV vaccine or HBVaxpro 40

Drug: Fendrix Fendrix suspension for injection GlaxoSmithKline Route of administration, dose regimen: Intra-muscular Dose: 20mcg of Hepatitis B Surface Antigen per vaccination at baseline, 1, 2 and 6 months.

Drug: HBVaxpro 40 Sanofi Pasteur MSD Route of administration, dose regimen: Intra-muscular Dose: 40mcg of Hepatitis B Surface Antigen per vaccination at baseline, 1 and 6 months.

Group Type: EXPERIMENTAL

Fendrix or HBVAXPRO 40

Intervention Type: BIOLOGICAL

To administer hepatitis B virus vaccines in patients with chronic liver disease that have not been previously vaccinated.

Interventions

Fendrix or HBVAXPRO 40

To administer hepatitis B virus vaccines in patients with chronic liver disease that have not been previously vaccinated.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Chronic liver disease patients -non-cirrhotic and cirrhotic- diagnosed by liver biopsy and / or non-invasive methods (by standard clinical, analytical and ultrasound crite-ria)
• Negative hepatitis B surface antigen (HBs Ag) and antibody to hepatitis B core antigen (anti-HBc).

Exclusion Criteria

• Allergy to vaccine components (sodium chloride, aluminium phosphate)
• Active or past HBV infection
• Patients previously vaccinated against HBV (regardless of response)
• Child-Pugh C
• Conditions that cause immunosuppression (HIV infection, chronic renal failure, active neoplasia)
• Pregnancy or breastfeeding
• Non-immunized HAV infection.

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

Sponsors

Corporacion Parc Tauli

OTHER

Sponsor Role: lead

Responsible Party

Diana Horta-Sangenis

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Diana Horta

Role: PRINCIPAL_INVESTIGATOR

Corporacion Parc Tauli

Locations

Hospital Universitari Mutua Terrassa

Terrassa, Barcelona/Spain, Spain

Countries

Spain

Other Identifiers

HMT2

Identifier Type: -

Identifier Source: org_study_id