A Study to Compare the Immune Response and Safety Elicited by Henogen's Adjuvanted Hepatitis B Vaccine Compared to Aventis Pasteur MSD's Hepatitis B Vaccine in Pre-Dialysis and Dialysis Patients Who Responded to Previous Hepatitis B Vaccination But Lost Antibody.

Study Overview
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Brief Summary
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The immune response of uraemic patients to hepatitis B vaccination is impaired compared to healthy subjects. After vaccination, anti-HBs peak antibody concentrations are reduced. As the persistence of anti-HBs is closely related to the initial anti-HBs peak, a more immunogenic vaccine, allowing higher antibody concentrations, would be a benefit for this population.

Detailed Description
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Study participants will receive either Henogen's adjuvanted hepatitis B vaccine or Aventis Pasteur's hepatitis B vaccine. The study involves a total of 3 visits and blood samples will taken at each of these visits.

Official Title
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A Phase III, Multicentric, Multinational, Controlled, Randomised, Open Study Comparing the Immunogenicity, Reactogenicity and Safety of Henogen's New Adjuvanted Hepatitis B Vaccine, HB-AS02V, to That of Aventis Pasteur MSD's Hepatitis B Vaccine, HBVAXPRO® , Administered as a Booster Dose in Pre-Dialysis, Peritoneal Dialysis and Haemodialysis Subjects (³ 15 Years of Age) Who Previously Responded to Hepatitis B Primary Vaccination But Have Lost Antibody.

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: HB-AS02V vaccine
* Biological: HBVAXPRO vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects whom the investigator believes that they can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study. A male or female subject 15 years of age or older at the time of the study entry. Written informed consent obtained from the subject/ subject's parents or guardians. Pre-dialysis patients, peritoneal dialysis patients and patients on haemodialysis. Pre-dialysis patients is defined as a subject with a documented creatinine clearance of les or equal to 30 ml/min. Seronegative for anti-HBc antibodies and for HBsAg at screening. Documented previous hepatitis B vaccination with one full primary course of licensed vaccine (the cumulative dose for primary vaccination is at least 160 mg of hepatitis B vaccine) with or without subsequent boosters. The last dose should have been administered at least three months before the planned dose of study vaccine in this study. Documented response to previous hepatitis B vaccination (i.e. anti-HBs antibody concentrations ³ 10 mIU/ml after primary vaccination or after booster/s with licensed vaccine), but for whom there is a loss of anti-HBs antibody concentrations below 10 mIU/ml at the time of inclusion into the study. Patients who have antibody concentrations below 50 mIU/ml at the time of inclusion will also be recruited provided that this antibody concentration is less than half of the highest documented antibody response achieved after primary vaccination or booster/s. The interval between the blood sample corresponding to the documented response and the hepatitis B vaccine dose received prior to this blood sample should be at least 25 days If the subject is female, she must be of non-childbearing potential, i.e., either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used medically-approved contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series. Exclusion Criteria: Subjects who have participated in the HN014/HBV-001 or HN017/HBV-003 study Use of any investigational or non-registered drug or vaccine within 30 days preceding the study vaccine administration, or planned use during the study period. Use of any registered vaccine within 7 days preceding the study vaccine administration. History of hepatitis B infection. Known exposure to hepatitis B virus within six months. Use of immunoglobulins within six months preceding the first study vaccination. Immunosuppression caused by the administration of parenteral steroids or chemotherapy (oral steroids are allowed). Any confirmed or suspected human immunodeficiency virus (HIV) infection. A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral/ axillary temperature < 37.5°C (or 37 °C in Czech Republic). Oral/axillary temperature equal or superior to 37.5 °C (or 37 °C in Czech Republic). Pregnant or lactating female

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>HB-AS02V vaccine | Biological: HB-AS02V vaccine<br>* HB-AS02V (20µg HBsAg) will be administered at Month 0<br>|
| Active Comparator: 2<br>HBVAXPRO vaccine | Biological: HBVAXPRO vaccine<br>* HBVAXPRO vaccine (40µg HBsAg) will be administered at Month 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-HBs antibody geometric mean concentrations. |  | Month 0 and Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection rates for all subjects |  | Months 0, 1 | 
| Seropositivity rates for all subjects |  | Month 0 and at Month 1 | 
| Percentage of subjects with anti-HBs antibody concentrations superior or equal to 100 mIU/ml for all subjects |  | Month 0 and at Month 1 | 
| Geometric Mean Concentration of anti-HBs antibodies for all subjects and for seropositive subjects |  | Month 0 and Month 1 | 
| Occurrence and intensity of solicited local signs and symptoms, relationship to vaccination of solicited general signs and symptoms during the 4-day follow-up after vaccination |  | Month 0 | 
| Occurrence, intensity and relationship to vaccination of unsolicited local and general signs and symptoms during the 31-day (Day 0 to Day 30) follow-up period after vaccination |  | Month 0 | 
| Occurrence, intensity and relationship to vaccination of all serious adverse events up to Month 1 |  | Month 0 to 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dialysis, Pre-dialysis, Hepatitis B vaccine, Prophylaxis hepatitis B infection