Phase IV, open, low-level intervention, clinical trial to compare the immunogenicity in immunosuppressed patients of an adjuvanted anti-hepatitis B vaccine with an anti-hepatitis B vaccine with increased antigenic load

• Register: EUCTR
• Last refreshed on: 18 March 2024
• Main ID: EUCTR2018-002368-18-ES
• Date of registration: 25/07/2018
• Prospective Registration: Yes
• Primary sponsor: FUNDACIÓ HOSPITAL UNIVERSITARI VALL D’HEBRON – INSTITUT DE RECERCA (VHIR)
• Public title: Phase IV, open, low-level intervention, clinical trial to compare the immunogenicity in immunosuppressed patients of an adjuvanted anti-hepatitis B vaccine with an anti-hepatitis B vaccine with increased antigenic load
• Scientific title: Phase IV, open, low-level intervention, clinical trial to compare the immunogenicity in immunosuppressed patients of an adjuvanted anti-hepatitis B vaccine with an anti-hepatitis B vaccine with increased antigenic load
• Date of first enrolment: 25/07/2018
• Target sample size: 740
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002368-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Spain

Contacts

• Name: ARO
• Affiliation: FUNDACIÓ HOSPITAL UNIVERSITARI VALL D’HEBRON – INSTITUT DE RECERCA (VHIR)

• Name: ARO
• Affiliation: FUNDACIÓ HOSPITAL UNIVERSITARI VALL D’HEBRON – INSTITUT DE RECERCA (VHIR)

Key inclusion & exclusion criteria

Inclusion criteria:
• Patients over 18 years of age, and diagnosed of:
- Autoimmune rheumatologic diseases under treatment with Rituximab or Infliximab
- Primary breast cancer or primary lung cancer
- Human Immunodeficiency Virus (HIV)
- Hematopoietic stem cell transplantation patients (HSCT), time since transplantation = 6 months
• Negative result of markers of hepatitis B virus infection (anti-core HBV antibody, hepatitis B virus surface antigen,
anti-HBV surface antigen antibody) in the last 3 months
• Life expectancy exceeding 1 year
• Written consent of the patient to participate in the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 740
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Hypersensitivity to the active ingredients or to any of the excipients of vaccines
• Documented history of infection or previous vaccination against HBV
• Infection with HIV (except in the subproject with HIV patients)
• Rejection of vaccination against HBV
• Difficulty of the patient to go to the study visits
• Presence of any other immune disorder different than the primary diagnosis


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

1. Autoinmune rheumatic diseases undertreated by rituximab or infliximab. 2. breast and lung cancer undertreated by chemotherapy 3. HIV 4. Haematopoietic progenitor cell transplantation (TCPH).
MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870
MedDRA version: 20.0 Level: PT Classification code 10058467 Term: Lung neoplasm malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
MedDRA version: 20.0 Level: PT Classification code 10063581 Term: Stem cell transplant System Organ Class: 10042613 - Surgical and medical procedures

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Fendrix suspension for injection
Hepatitis B (rDNA) vaccine (adjuvanted, adsorbed).
Product Name: Fendrix
Product Code: Fendrix
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Fendrix suspension for injection Hepatitis B (rDNA) vaccine (adjuvanted, adsorbed).
Other descriptive name: HEPATITIS B VACCINE (RDNA)
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection
Hepatitis B vaccine (rDNA)
Product Name: HBVAXPRO® 40 micrograms
Product Code: HBVAXPRO® 40 micrograms
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: HBVAXPRO 5 micrograms/0.5 ml Suspension for injection Hepatitis B vaccine (rDNA)
Other descriptive name: HEPATITIS B VIRUS SURFACE ANTIGEN RECOMBINANT (S PROTEIN)
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: To compare the proportion of patients with protective levels of antibodies against HBV at 3 months after the first
dose, in immunosuppressed patients, between those vaccinated with an anti-hepatitis B vaccine adjuvanted with
1. To compare the proportion of patients with protective levels of antibodies against HBV at 7 and 12 months
after the first dose, in immunosuppressed patients, between those vaccinated with anti-hepatitis B vaccine
adjuvanted with AS04C and those vaccinated with an increased antigenic load.
2. To compare the levels of antibodies against HBV at 3, 7 and 12 months of the first dose, in
immunosuppressed patients, between patients vaccinated with anti-hepatitis B vaccine adjuvanted with
AS04C and those vaccinated with an increased antigenic load vaccine.
3. To describe all adverse events that could appear during research.

Main Objective: To compare the proportion of patients with protective levels of antibodies against HBV at 3 months after the first
dose, in immunosuppressed patients, between those vaccinated with an anti-hepatitis B vaccine adjuvanted with
AS04C versus those vaccinated with anti-hepatitis B vaccine with increased antigenic load.

Primary end point(s): Main variable for vaccine response assessment (immunogenicity):
Level of antibodies against HBV surface antigen (HBsAg) one month after the third dose =10UI, which will be
determined by enzyme-immunoassay.

Timepoint(s) of evaluation of this end point: During the clinical trial.

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints of immunogenicity:
• Level of antibodies against HBV surface antigen at the end of the vaccination schedule, which will be determined by
enzyme-immunoassay between 1 and 2 months after the last dose.
• Level of antibodies against HBV surface antigen one year after the end of the vaccination schedule, which will be
determined by enzyme-immunoassay
(Patients will be considered responders to the vaccine when the antibody titer against HBsAg is equal to or greater
than 10IU/l. In the patients who don’t respond after the last dose of vaccination the determination at 12 months won’t
be performed. These non-responding patients will receive the usual clinical pattern, revaccination with a second
complete series, and there would be no more follow-up from the study).
Descriptive variables of subgroups:
- HIV patients:
• Level of CD4 lymphocytes and determination of viral load one month before the first dose, one month after
the third dose, between one and two months after the last dose, and 12 months after the first dose.
-HSCT patients:
• Follow up to detect any evidence of Graft-Versus-Host-Disease (GVHD)
• Type of transplant, autologous or allogeneic
• Clinical condition that cause the transplant
-Rheumatologic patients:
• Main clinical condition
• Date of diagnosis
• Other immunosuppressive treatment (besides Rituximab or Infliximab: type of drug, start and end time)
-Cancer patients:
• Stage of cancer
• Date of diagnosis
• Histological type of cancer
• Treatment (chemotherapy): start and end time

Timepoint(s) of evaluation of this end point: During the clinical trial.

Secondary ID(s)

HEPB-VAC-01

Source(s) of Monetary Support

Beca La Marató 2017 de TV3 (26ª edición)

Ethics review

Status: Approved
Approval date: 11/07/2018
Contact: