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

Study Overview
=================
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.

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

Conditions
-----------------
Meningococcal Disease, Meningococcal Meningitis, Hepatitis A, Hepatitis B

Intervention / Treatment
-----------------
* Biological: MenACWY-CRM
* Biological: Combined inactivated hepatitis A & recombinant hepatitis B
* Biological: Recombinant hepatitis B vaccine
* Biological: Inactivated hepatitis A vaccine


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>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<br>* 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.<br>Biological: Recombinant hepatitis B vaccine<br>* Recombinant hepatitis B vaccine will be administered intramuscularly on days 8 and 29<br>Biological: Inactivated hepatitis A vaccine<br>* Inactivated hepatitis A will be administered intramuscularly on days 8 and 29.<br>|
| Active Comparator: Group 2<br>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<br>* Novartis meningococcal ACWY conjugate vaccine will be administered intramuscularly (IM) on day 1.<br>Biological: Combined inactivated hepatitis A & recombinant hepatitis B<br>* 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.<br>Biological: Recombinant hepatitis B vaccine<br>* Recombinant hepatitis B vaccine will be administered intramuscularly on days 8 and 29<br>Biological: Inactivated hepatitis A vaccine<br>* Inactivated hepatitis A will be administered intramuscularly on days 8 and 29.<br>|
| Active Comparator: Group 3<br>This group will receive only MenACWY-CRM. | Biological: MenACWY-CRM<br>* Novartis meningococcal ACWY conjugate vaccine will be administered intramuscularly (IM) on day 1.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 57 (previously unprimed subjects) day 29 (previously primed subjects) postvaccination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 28 days post 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. | 28 days postvaccination (day 29). | 
| 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. | 28 days post vaccination (day 29). | 
| 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). | Day 1 to day 57. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
meningococcal, conjugate, vaccine, adults