Hepatitis B Vaccine for Non-responders

NCT03415672 | Completed Phase 2 DMC

• 2 other identifiers: HBnr022016-002720-91
• Study Type: interventional
• Target: 133
• Locations: 2 countries
• Sites: 3

Brief Summary

In the current study, the investigators study the efficacy of the HBAI20 vaccine to induce seroprotection in registered non-responders (adults who were previously vaccinated with the HBVaxPro-10μg but did not achieve seroprotection). The study will further assess the safety of the HBAI20 vaccine in comparison with HBVaxPro-10μg.

Conditions

Hepatitis B

Keywords

Interleukin-2; Hepatitis B Vaccines; Non-responders; Liver Diseases; Digestive system; Vaccines

Outcome Measures

Primary Outcomes (1)

• Immunogenicity of the HBAI20

  Anti Hepatitis B surface antigen antibody titer.

  Six weeks after the third vaccination.

Secondary Outcomes (1)

• Safety of the HBAI20 Hepatitis B vaccine: Percentage of subjects reporting adverse events after being vaccinated.

  The whole duration of the study protocol (102 days)

Study Arms (2)

Group 1

ACTIVE COMPARATOR

Subjects included in Group 1 are adults who are non-responders (did not achieve seroprotection after 3 or more vaccinations with a Hepatitis B vaccine. They will receive three doses of HBVaxPro-10μg at 0, 1, and 2 months. The HBVaxPro-10μg vaccines are administered strictly intramuscularly in the deltoid muscle and must not be injected intravascularly.

Biological: HBVaxPro

Group 2

EXPERIMENTAL

Subjects included in Group 2 are adults who are non-responders (did not achieve seroprotection after 3 or more vaccinations with a Hepatitis B vaccine). They will receive three doses of HBAI20 at 0, 1, and 2 months. The HBAI20 vaccines are administered strictly intramuscularly in the deltoid muscle and must not be injected intravascularly.

Biological: HBAI20

Interventions

HBVaxPro BIOLOGICAL

Three doses of HBVaxPro-10μg at 0, 1, and 2 months. The HBVaxPro-10μg vaccines are administered strictly intramuscularly in the deltoid muscle and must not be injected intravascularly.

Group 1

HBAI20 BIOLOGICAL

Three doses of HBAI20 at 0, 1, and 2 months. The HBAI20 vaccines are administered strictly intramuscularly in the deltoid muscle and must not be injected intravascularly.

Group 2

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In good health as determined by the outcome of medical history, physical examination screening/baseline labs and clinical judgment of the clinical investigator
• Age 18 to 59 years, inclusive at the time of enrollment
• Willing and able to adhere to the study regimen
• Willing to adhere to a highly effective birth control method during the duration of the study
• Having a signed informed consent form
• Documented non-responders: Subjects with documented one or more cycles of Hepatitis B vaccination (total of 3 or more vaccinations) and titer analysis 1 to 3 months after the last vaccination that show that they have not developed the Hepatitis B antibody titer recommended after standard vaccination: HBsAg antibody titer superior to 10mIU/ml. In case the subjects do not have a titer analysis performed 1 to 3 months after their last recorded vaccination, the potential subject can be included after permission from the project leader after analysis of the case file.

You may not qualify if:

• Any infectious disease at the time of screening and/or enrollment
• Positive HIV, Hepatitis B virus or Hepatitis C virus serology
• Known or suspected immune deficiency
• Known or suspected disease that influences the immune system including chronic allergies that require frequent anti-allergy medication - excluding anti-histaminics -, cancer and transplantation recipients
• Known or suspected allergy to any of the vaccine components
• Dialysis patient
• History of unusual or severe reactions to any previous vaccination
• History of any neurologic disorder, including epilepsy and autism
• Use of medication that influences the immune system (immune suppressive treatment or daily use of corticosteroids, including chronic use of local corticosteroids)
• Any vaccination within 3 months before screening excluding flu vaccination
• Blood donation within 1 month before screening
• Administration of plasma (incl. immunoglobulins) or blood products within 12 months before screening
• Participation in another clinical trial within 3 months before screening
• Abnormal pre-treatment laboratory parameters which are clinically relevant according to the investigator
• Bleeding disorders. Participants on coumadins anticoagulants and participants receiving 2 platelet aggregation inhibitors can not be included in the study. People on the direct oral anticoagulant dabigatran, apixaban, edoxaban, and rivaroxaban and participants using only one platelet aggregation inhibitor can be included.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• CyTuVax: collaborator

Study Sites (3)

Vaxinfectio - Antwerp University

Antwerp, Belgium

Location

Ziekenhuis Oost-Limburg

Genk, Belgium

Location

Maastricht UMC

Maastricht, 6202 AZ, Netherlands

Location

Related Publications (13)

• Coates T, Wilson R, Patrick G, Andre F, Watson V. Hepatitis B vaccines: assessment of the seroprotective efficacy of two recombinant DNA vaccines. Clin Ther. 2001 Mar;23(3):392-403. doi: 10.1016/s0149-2918(01)80044-8.

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• Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999 Feb;179(2):489-92. doi: 10.1086/314578.

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• Yu AS, Cheung RC, Keeffe EB. Hepatitis B vaccines. Infect Dis Clin North Am. 2006 Mar;20(1):27-45. doi: 10.1016/j.idc.2006.01.004.

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• Cardell K, Akerlind B, Sallberg M, Fryden A. Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine. J Infect Dis. 2008 Aug 1;198(3):299-304. doi: 10.1086/589722.

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• Halperin SA, Dobson S, McNeil S, Langley JM, Smith B, McCall-Sani R, Levitt D, Nest GV, Gennevois D, Eiden JJ. Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults. Vaccine. 2006 Jan 9;24(1):20-6. doi: 10.1016/j.vaccine.2005.08.095. Epub 2005 Sep 12.

  PMID: 16198027 BACKGROUND

• Halperin SA, Ward BJ, Dionne M, Langley JM, McNeil SA, Smith B, Mackinnon-Cameron D, Heyward WL, Martin JT. Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine. Hum Vaccin Immunother. 2013 Jul;9(7):1438-44. doi: 10.4161/hv.24256. Epub 2013 Apr 9.

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• Ambrosch F, Wiedermann G, Kundi M, Leroux-Roels G, Desombere I, Garcon N, Thiriart C, Slaoui M, Thoelen S. A hepatitis B vaccine formulated with a novel adjuvant system. Vaccine. 2000 Apr 14;18(20):2095-101. doi: 10.1016/s0264-410x(99)00566-6.

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• Desombere I, Van der Wielen M, Van Damme P, Stoffel M, De Clercq N, Goilav C, Leroux-Roels G. Immune response of HLA DQ2 positive subjects, vaccinated with HBsAg/AS04, a hepatitis B vaccine with a novel adjuvant. Vaccine. 2002 Jun 7;20(19-20):2597-602. doi: 10.1016/s0264-410x(02)00150-0.

  PMID: 12057618 BACKGROUND

• Jacques P, Moens G, Desombere I, Dewijngaert J, Leroux-Roels G, Wettendorff M, Thoelen S. The immunogenicity and reactogenicity profile of a candidate hepatitis B vaccine in an adult vaccine non-responder population. Vaccine. 2002 Nov 1;20(31-32):3644-9. doi: 10.1016/s0264-410x(02)00397-3.

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  PMID: 1418698 BACKGROUND

MeSH Terms

Conditions

Hepatitis B; Liver Diseases

Interventions

Hepatitis B Vaccines

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Pierre van Damme, MD, PhD

  Vaxinfectio - Antwerp University

  PRINCIPAL INVESTIGATOR

• Geert Robaeys, MD, PhD

  Ziekenhuis Oost-Limburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 30, 2018
• Study Start: October 11, 2017
• Primary Completion: January 9, 2019
• Study Completion: January 9, 2019
• Last Updated: January 31, 2019

Record last verified: 2019-01

Locations

NL (1); BE (2)