Study to Evaluate the Safety and Immunogenicity of Combined Hepatitis A/B Vaccine With MenACWY-CRM Conjugate Vaccine

This study has been completed.
Sponsor:
Collaborator:
Novartis Vaccines
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT01453348
First received: October 3, 2011
Last updated: March 3, 2016
Last verified: March 2016
  Purpose
This study compares the safety and immunogenicity profile of combined hepatitis A/B vaccine given alone or concomitantly with MenACWY-CRM to healthy adults.

Condition Intervention Phase
Meningococcal Disease
Meningococcal Meningitis
Hepatitis A
Hepatitis B
Biological: MenACWY-CRM
Biological: Combined inactivated hepatitis A & recombinant hepatitis B
Biological: Recombinant hepatitis B vaccine
Biological: Inactivated hepatitis A vaccine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Immunogenicity of Combined Hepatitis A/B Vaccine When Administered Concomitantly With Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Adults

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Geometric Mean antiHAV and antiHBV Concentrations (GMCs), 28 Days After Primary and Booster Vaccination [ Time Frame: Day 57 (previously unprimed subjects) day 29 (previously primed subjects) postvaccination. ] [ Designated as safety issue: No ]
    Assessment was made to demonstrate the non-inferiority of hepatitis A/B vaccine with MenACWY-CRM as compared to hepatitis A/B vaccine without MenACWY-CRM, as measured by geometric mean concentrations on day 57 in previously unvaccinated subjects or on day 29 after a booster dose in previously vaccinated subjects.


Secondary Outcome Measures:
  • Percentages of Subjects With antiHAV and antiHBsAg Antibodies Concentrations Above Seroprotection Level 28 Days After Primary or Booster Vaccination [ Time Frame: 28 days post primary or booster vaccination. ] [ Designated as safety issue: No ]
    Immunogenicity was assessed as the percentages of subjects with anti-HAV concentration ≥20 mIU/mL and anti- HBsAg antibody concentration ≥10 mIU/mL, 28 days after primary or booster vaccination.

  • Percentages of Subjects With Seroresponse Against N Meningitidis A, C, W and Y Serogroups at Day 29 [ Time Frame: 28 days postvaccination (day 29). ] [ Designated as safety issue: No ]

    Immunogenicity was assessed as the seroresponse rates for meningococcal serogroups A, C, W and Y elicited by MenACWY-CRM on day 29 when given concomitantly with combined hepatitis A/B vaccine or given alone.

    For a subject with a baseline hSBA titer < 1:4, seroresponse is defined as a postvaccination hSBA titer ≥1:8; for a subject with a baseline hSBA titer ≥ 1:4, seroresponse is defined as a postvaccination hSBA titer of at least 4 times the baseline.


  • hSBA GMTs Assay Titers Against N Meningitidis A, C, W and Y Serogroups at Day 29 [ Time Frame: 28 days post vaccination (day 29). ] [ Designated as safety issue: No ]
    Immunogenicity was assessed in terms of geometric mean titers (GMTs) of antibodies to meningococcal serogroups A, C, W and Y on day 29 when given concomitantly with combined hepatitis A/B vaccine or given alone.

  • Percentages of Subjects With Unsolicited Adverse Events (AEs) [ Time Frame: Day 1 to day 57. ] [ Designated as safety issue: Yes ]
    Safety was assessed in terms of percentage of all spontaneously reported AEs collected from the time the subject signed the informed consent form (day 1), until the subject stopped study participation (day 57).


Enrollment: 252
Study Start Date: October 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
This group will receive Inactivated hepatitis A and recombinant hepatitis B or 'Combined inactivated hepatitis A & recombinant hepatitis B vaccine' alone on the different visits.
Biological: Combined inactivated hepatitis A & recombinant hepatitis B
Combined inactivated hepatitis A and recombinant hepatitis B vaccine will be administered by IM on days 1, 8 & 29 for subjects unprimed with hepatitis A and B; and a single booster injection on day 1 for primed subjects.
Biological: Recombinant hepatitis B vaccine
Recombinant hepatitis B vaccine will be administered intramuscularly on days 8 and 29
Biological: Inactivated hepatitis A vaccine
Inactivated hepatitis A will be administered intramuscularly on days 8 and 29.
Active Comparator: Group 2
This group will receive Inactivated hepatitis A vaccine and recombinant hepatitis B Vaccine or 'Combined inactivated hepatitis A & recombinant hepatitis B vaccine' concomitantly with MenACWY-CRM.
Biological: MenACWY-CRM
Novartis meningococcal ACWY conjugate vaccine will be administered intramuscularly (IM) on day 1.
Biological: Combined inactivated hepatitis A & recombinant hepatitis B
Combined inactivated hepatitis A and recombinant hepatitis B vaccine will be administered by IM on days 1, 8 & 29 for subjects unprimed with hepatitis A and B; and a single booster injection on day 1 for primed subjects.
Biological: Recombinant hepatitis B vaccine
Recombinant hepatitis B vaccine will be administered intramuscularly on days 8 and 29
Biological: Inactivated hepatitis A vaccine
Inactivated hepatitis A will be administered intramuscularly on days 8 and 29.
Active Comparator: Group 3
This group will receive only MenACWY-CRM.
Biological: MenACWY-CRM
Novartis meningococcal ACWY conjugate vaccine will be administered intramuscularly (IM) on day 1.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Individuals eligible for enrollment in this study were female and male subjects who had shown to be healthy and who were:

  1. Between 18 and 64 years of age inclusive and who had given their written informed consent;
  2. Available for all visits and telephone calls scheduled for the study;
  3. In good health as determined by medical history, physical examination and clinical judgment of the investigator;
  4. For female subjects, had a negative urine pregnancy test.

Exclusion Criteria:

Individuals not eligible to be enrolled in the study were those:

  1. Who were breastfeeding.
  2. Who had a previous personal history of Neisseria meningitidis, hepatitis A or hepatitis B infection.
  3. Who received previous immunization with any meningococcal vaccine.
  4. Who received previous hepatitis A and/or B vaccination, determined by history (interview of the subject) and/or by review of his or her vaccination card, if less than 5 years have elapsed since vaccination.
  5. Who received investigational agents or vaccines within 30 days prior to enrollment or who expected to receive an investigational agent or vaccine prior to completion of the study.
  6. Who received live licensed vaccines within 30 days and inactive vaccine within 15 days prior to enrollment or for whom receipt of a licensed vaccine was anticipated during the study period (Exception: Influenza vaccine might have been administered up to 15 days prior to each study immunization and no less than 15 days after each study immunization).
  7. Who experienced, within the 7 days prior to enrollment, significant acute infection (for example requiring systemic antibiotic treatment or antiviral therapy) or had experienced fever (defined as body temperature ≥ 38°C) within 3 days prior to enrollment.
  8. Who had any serious acute, chronic or progressive disease such as:

    • History of cancer
    • Complicated diabetes mellitus
    • Advanced arteriosclerotic disease
    • Autoimmune disease
    • HIV infection or AIDS
    • Blood dyscrasias
    • Congestive heart failure
    • Renal failure
    • Severe malnutrition (Note: Subjects with mild asthma were eligible for enrollment. Subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids were not eligible for enrollment).
  9. Who had epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome.
  10. Who had a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including but not limited to latex allergy and antibiotic allergy.
  11. Who had a known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from (for example):

    • Receipt of immunosuppressive therapy within 30 days prior to enrollment (systemic corticosteroids administered for more than 5 days, or in a daily dose > 1 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy);
    • Receipt of immunostimulants;
    • Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 90 days prior to enrollment and for the full length of the study.
  12. Who were known to have a bleeding diathesis, or any condition that might have been associated with a prolonged bleeding time.
  13. Who had any condition that, in the opinion of the investigator, might have interfered with the evaluation of the study objectives.
  14. Who were part of the study personnel or close family members of those conducting this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01453348

Locations
Germany
03, Novartis Investigational Site
Berlin, Germany, 10117
02, Novartis Investigational Site
Hamburg, Germany, 20359
01, Novartis Investigational Site
München, Germany, 80802
04, Novartis Investigational Site
Rostock, Germany, 18057
Sponsors and Collaborators
Novartis
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines Novartis Vaccines
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01453348     History of Changes
Other Study ID Numbers: V59_53  2011-001333-17 
Study First Received: October 3, 2011
Results First Received: October 22, 2013
Last Updated: March 3, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
meningococcal
conjugate
vaccine
adults

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Meningitis
Meningococcal Infections
Meningitis, Meningococcal
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Central Nervous System Diseases
Nervous System Diseases
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Meningitis, Bacterial
Central Nervous System Bacterial Infections
Central Nervous System Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016