search
Back to results

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

Primary Purpose

Meningococcal Disease, Meningococcal Meningitis, Hepatitis A

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
MenACWY-CRM
Combined inactivated hepatitis A & recombinant hepatitis B
Recombinant hepatitis B vaccine
Inactivated hepatitis A vaccine
Sponsored by
Novartis Vaccines
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Meningococcal Disease focused on measuring meningococcal, conjugate, vaccine, adults

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • 03, Novartis Investigational Site
  • 02, Novartis Investigational Site
  • 01, Novartis Investigational Site
  • 04, Novartis Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Group 1

Group 2

Group 3

Arm Description

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.

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.

This group will receive only MenACWY-CRM.

Outcomes

Primary Outcome Measures

Geometric Mean antiHAV and antiHBV Concentrations (GMCs), 28 Days After Primary and Booster Vaccination
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
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
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
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)
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).

Full Information

First Posted
October 3, 2011
Last Updated
May 8, 2017
Sponsor
Novartis Vaccines
Collaborators
GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT01453348
Brief Title
Study to Evaluate the Safety and Immunogenicity of Combined Hepatitis A/B Vaccine With MenACWY-CRM Conjugate Vaccine
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Vaccines
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study compares the safety and immunogenicity profile of combined hepatitis A/B vaccine given alone or concomitantly with MenACWY-CRM to healthy adults.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningococcal Disease, Meningococcal Meningitis, Hepatitis A, Hepatitis B
Keywords
meningococcal, conjugate, vaccine, adults

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
252 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Group 2
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Group 3
Arm Type
Active Comparator
Arm Description
This group will receive only MenACWY-CRM.
Intervention Type
Biological
Intervention Name(s)
MenACWY-CRM
Intervention Description
Novartis meningococcal ACWY conjugate vaccine will be administered intramuscularly (IM) on day 1.
Intervention Type
Biological
Intervention Name(s)
Combined inactivated hepatitis A & recombinant hepatitis B
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Recombinant hepatitis B vaccine
Intervention Description
Recombinant hepatitis B vaccine will be administered intramuscularly on days 8 and 29
Intervention Type
Biological
Intervention Name(s)
Inactivated hepatitis A vaccine
Intervention Description
Inactivated hepatitis A will be administered intramuscularly on days 8 and 29.
Primary Outcome Measure Information:
Title
Geometric Mean antiHAV and antiHBV Concentrations (GMCs), 28 Days After Primary and Booster Vaccination
Description
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.
Time Frame
Day 57 (previously unprimed subjects) day 29 (previously primed subjects) postvaccination.
Secondary Outcome Measure Information:
Title
Percentages of Subjects With antiHAV and antiHBsAg Antibodies Concentrations Above Seroprotection Level 28 Days After Primary or Booster Vaccination
Description
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.
Time Frame
28 days post primary or booster vaccination.
Title
Percentages of Subjects With Seroresponse Against N Meningitidis A, C, W and Y Serogroups at Day 29
Description
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.
Time Frame
28 days postvaccination (day 29).
Title
hSBA GMTs Assay Titers Against N Meningitidis A, C, W and Y Serogroups at Day 29
Description
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.
Time Frame
28 days post vaccination (day 29).
Title
Percentages of Subjects With Unsolicited Adverse Events (AEs)
Description
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).
Time Frame
Day 1 to day 57.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Individuals eligible for enrollment in this study were female and male subjects who had shown to be healthy and who were: Between 18 and 64 years of age inclusive and who had given their written informed consent; Available for all visits and telephone calls scheduled for the study; In good health as determined by medical history, physical examination and clinical judgment of the investigator; For female subjects, had a negative urine pregnancy test. Exclusion Criteria: Individuals not eligible to be enrolled in the study were those: Who were breastfeeding. Who had a previous personal history of Neisseria meningitidis, hepatitis A or hepatitis B infection. Who received previous immunization with any meningococcal vaccine. 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. 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. 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). 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. 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). Who had epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome. 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. 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. Who were known to have a bleeding diathesis, or any condition that might have been associated with a prolonged bleeding time. Who had any condition that, in the opinion of the investigator, might have interfered with the evaluation of the study objectives. Who were part of the study personnel or close family members of those conducting this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Vaccines
Organizational Affiliation
Novartis Vaccines
Official's Role
Study Chair
Facility Information:
Facility Name
03, Novartis Investigational Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
02, Novartis Investigational Site
City
Hamburg
ZIP/Postal Code
20359
Country
Germany
Facility Name
01, Novartis Investigational Site
City
München
ZIP/Postal Code
80802
Country
Germany
Facility Name
04, Novartis Investigational Site
City
Rostock
ZIP/Postal Code
18057
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
25483566
Citation
Alberer M, Burchard G, Jelinek T, Reisinger EC, Meyer S, Forleo-Neto E, Dagnew AF, Arora AK. Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults. J Travel Med. 2015 Mar-Apr;22(2):105-14. doi: 10.1111/jtm.12180. Epub 2014 Dec 7.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs