Combination Hepatitis A and B Vaccine to Induce Immunity in Non-responders

NCT01126853 | Withdrawn Phase 4 DMC

• 2 other identifiers: MSH 09-0220-ER09-15
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatitis B is a vaccine preventable infection which can be transmitted through occupational exposure. Approximately 15% of patients will not respond to an initial series of vaccination. Of those re-vaccinated approximately fifty percent will respond. On the basis of poor response to a third series, repeat vaccination is not recommended and non-responders are considered vulnerable to infection. Cardell studied the use of double dose combination hepatitis A and B vaccine (Twinrix) in non responders who had received four or more doses previously and found a high response rate suggesting this vaccine and dose could be effective. The investigators study seeks to duplicate the findings of Cardell, using a more strict definition of non-responder (6 or more previous doses).

Conditions

Hepatitis B

Keywords

Immunization; Immunity; Prevention

Outcome Measures

Primary Outcomes (1)

• Protective immunity to Hepatitis B

  The number of patients who develop protective antibody titres (\>10 mIU/ml) during the immunization period. This will be followed 1 month after each dose received.

  up to 7 months (average)

Secondary Outcomes (3)

• Adverse Events

  up to 7 months (average)

• Rate of Recruitment

  1 year

• Partial immunity to Hepatitis B

  up to 7 months (average)

Study Arms (1)

Vaccination

EXPERIMENTAL

Receipt of up to 3 series of double dose combination hepatitis A/B vaccine (Twinrix)

Biological: Twinrix

Interventions

Twinrix BIOLOGICAL

Up to three intramuscular doses of 1cc of Twinrix (combined hepatitis A/B vaccine) at 0, 1, and 6 months post-enrollment

Vaccination

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have an understanding of the study, agree to its provisions, and give written informed consent prior to study entry.
• Available for follow-up during the study period.
• Has had at least two complete courses of monovalent hepatitis B vaccine, and has documented antiHbS IgG titers of \<10mIU/ml within 6 months of completion of the most recent course of vaccination.

You may not qualify if:

• Allergic to any components of the vaccine.
• Previous serious adverse events associated with the hepatitis B vaccine
• Received one or more doses of Twinrix in the past
• Chronic hepatitis B infection, defined as ever having had a positive HBSAg, HBCAb or HepB RNA test
• Pregnant, or planning to become pregnant during the study period.
• Received dose of hepatitis B immune globulin, or immune globulin, in last 6 months
• Immunocompromising condition or therapy that would be expected to reduce the efficacy of vaccination, including:
• HIV infection;
• lymphoma, multiple myeloma, leukemia or other blood dyscrasia;
• systemic lupus erythematosis or other connective tissue disorder;
• renal failure (baseline serum creatinine \>150uM, or requires dialysis);
• nephrotic syndrome;
• active neoplastic disease (except localized skin cancer);
• any requirement for corticosteroids \>20mg/day for \>1 week in the six months prior to randomization;
• cytotoxic therapy (e.g. chemotherapy for cancer) received within the six months prior to randomization

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• University of Toronto: collaborator

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G 1K5, Canada

Location

Related Publications (17)

• 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.

  PMID: 18544037 BACKGROUND

• Alavian SM, Mansouri S, Abouzari M, Assari S, Bonab MS, Miri SM. Long-term efficacy of hepatitis B vaccination in healthcare workers of Oil Company Hospital, Tehran, Iran (1989-2005). Eur J Gastroenterol Hepatol. 2008 Feb;20(2):131-4. doi: 10.1097/MEG.0b013e3282f1cc28.

  PMID: 18188034 BACKGROUND

• Chen W, Gluud C. Vaccines for preventing hepatitis B in health-care workers. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD000100. doi: 10.1002/14651858.CD000100.pub3.

  PMID: 16235273 BACKGROUND

• Clemens R, Sanger R, Kruppenbacher J, Hobel W, Stanbury W, Bock HL, Jilg W. Booster immunization of low- and non-responders after a standard three dose hepatitis B vaccine schedule--results of a post-marketing surveillance. Vaccine. 1997 Mar;15(4):349-52. doi: 10.1016/s0264-410x(96)00205-8.

  PMID: 9141203 BACKGROUND

• Craven DE, Awdeh ZL, Kunches LM, Yunis EJ, Dienstag JL, Werner BG, Polk BF, Syndman DR, Platt R, Crumpacker CS, et al. Nonresponsiveness to hepatitis B vaccine in health care workers. Results of revaccination and genetic typings. Ann Intern Med. 1986 Sep;105(3):356-60. doi: 10.7326/0003-4819-105-3-356.

  PMID: 2943202 BACKGROUND

• Czeschinski PA, Binding N, Witting U. Hepatitis A and hepatitis B vaccinations: immunogenicity of combined vaccine and of simultaneously or separately applied single vaccines. Vaccine. 2000 Jan 6;18(11-12):1074-80. doi: 10.1016/s0264-410x(99)00354-0.

  PMID: 10590328 BACKGROUND

• Das K, Gupta RK, Kumar V, Kar P. Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders. World J Gastroenterol. 2003 May;9(5):1132-4. doi: 10.3748/wjg.v9.i5.1132.

  PMID: 12717874 BACKGROUND

• Goldwater PN. Randomized comparative trial of interferon-alpha versus placebo in hepatitis B vaccine non-responders and hyporesponders. Vaccine. 1994 Apr;12(5):410-4. doi: 10.1016/0264-410x(94)90116-3.

  PMID: 8023548 BACKGROUND

• Goldwater PN. Randomized, comparative trial of 20 micrograms vs 40 micrograms Engerix B vaccine in hepatitis B vaccine non-responders. Vaccine. 1997 Mar;15(4):353-6. doi: 10.1016/s0264-410x(96)00202-2.

  PMID: 9141204 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.

  PMID: 12399191 BACKGROUND

• Rendi-Wagner P, Shouval D, Genton B, Lurie Y, Rumke H, Boland G, Cerny A, Heim M, Bach D, Schroeder M, Kollaritsch H. Comparative immunogenicity of a PreS/S hepatitis B vaccine in non- and low responders to conventional vaccine. Vaccine. 2006 Apr 5;24(15):2781-9. doi: 10.1016/j.vaccine.2006.01.007. Epub 2006 Jan 19.

  PMID: 16455169 BACKGROUND

• Rottinghaus ST, Poland GA, Jacobson RM, Barr LJ, Roy MJ. Hepatitis B DNA vaccine induces protective antibody responses in human non-responders to conventional vaccination. Vaccine. 2003 Nov 7;21(31):4604-8. doi: 10.1016/s0264-410x(03)00447-x.

  PMID: 14575774 BACKGROUND

• U.S. Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001 Jun 29;50(RR-11):1-52.

  PMID: 11442229 BACKGROUND

• Westmoreland D, Player V, Heap DC, Hammond A. Immunization against hepatitis B--what can we expect? Results of a survey of antibody response to immunization in persons 'at risk' of occupational exposure to hepatitis B. Epidemiol Infect. 1990 Jun;104(3):499-509. doi: 10.1017/s0950268800047506.

  PMID: 2140795 BACKGROUND

• Wismans P, van Hattum J, Stelling T, Poel J, de Gast GC. Effect of supplementary vaccination in healthy non-responders to hepatitis B vaccination. Hepatogastroenterology. 1988 Apr;35(2):78-9.

  PMID: 2967237 BACKGROUND

• Yasumura S, Shimizu Y, Yasuyama T, Hiroki O, Okada K, Tsukishiro T, Tsuchida T, Higuchi K, Watanabe A. Intradermal hepatitis B virus vaccination for low- or non-responded health-care workers. Acta Med Okayama. 1991 Dec;45(6):457-9. doi: 10.18926/AMO/32181.

  PMID: 1838229 BACKGROUND

• Zuckerman JN, Zuckerman AJ, Symington I, Du W, Williams A, Dickson B, Young MD; UK Hepacare Study Group. Evaluation of a new hepatitis B triple-antigen vaccine in inadequate responders to current vaccines. Hepatology. 2001 Oct;34(4 Pt 1):798-802. doi: 10.1053/jhep.2001.27564.

  PMID: 11584378 BACKGROUND

MeSH Terms

Conditions

Hepatitis B

Interventions

twinrix

Condition Hierarchy (Ancestors)

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

Study Officials

• Todd C Lee, MD

  Mount Sinai Hospital, University of Toronto

  PRINCIPAL INVESTIGATOR

• Allison J McGeer, MD MSc

  Mount Sinai Hospital, University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 15, 2010
• First Posted: May 20, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: July 1, 2011
• Last Updated: June 1, 2020

Record last verified: 2020-05

Locations

CA (1)