A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Immunogenicity of Select Travel Vaccines When Administered Concomitantly With MenACWY in Adults

Study Overview
=================
Brief Summary
-----------------
This study compares the safety and immunogenicity profile of several travel vaccines 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 Select Travel Vaccines When Administered Concomitantly With Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Adults

Conditions
-----------------
Meningococcal Disease, Meningococcal Meningitis, Typhoid, Yellow Fever, Rabies, Japanese Encephalitis

Intervention / Treatment
-----------------
* Biological: Typhoid Vi Polysaccharide Vaccine
* Biological: Yellow Fever Vaccine
* Biological: Japanese Encephalitis Vaccine
* Biological: Rabies Vaccine
* Biological: MenACWY-CRM Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female and male subjects who must be healthy and must be: Between 18 and 60 years of age inclusive and who have 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, having a negative urine pregnancy test. Exclusion Criteria: Individuals not eligible to be enrolled in the study are those: who are breastfeeding; who have a personal history of Neisseria meningitidis infection, typhoid fever, rabies, or any flavivirus infection (e.g., Japanese encephalitis, tick-borne encephalitis, yellow fever, dengue fever, West Nile virus infection); who have been immunized with any of the study vaccines within the last five years as determined by medical history and/or vaccination card; who have received investigational agents or vaccines within 30 days prior to enrollment or who expect to receive an investigational agent or vaccine prior to completion of the study; who have received live licensed vaccines within 30 days and inactive vaccine within 15 days prior to enrollment or for whom receipt of a licensed vaccine is anticipated during the study period. (Exception: Influenza vaccine may be administered up to 15 days prior to each study immunization and no less than 15 days after each study immunization); who have received an anti-malaria drug, up to 2 months prior to the study; who have experienced, within the 7 days prior to enrollment, significant acute infection (for example requiring systemic antibiotic treatment or antiviral therapy) or have experienced fever (defined as body temperature ≥ 38°C) within 3 days prior to enrollment; who have 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 are eligible for enrollment. Subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids are not eligible for enrollment); who have epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome; who have a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including but not limited to latex allergy, egg allergy, antibiotic allergy, chicken proteins or gelatin allergy; who have 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 are known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time; who have myasthenia gravis; thyroid or thymic disorders, who have any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives; who are part of the study personnel or close family members of those conducting this study. for whom a long-term stay (≥ 1 month) was planned in Africa, Latin America, or Asia.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 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: TF+YF<br>Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide and yellow fever vaccine. | Biological: Typhoid Vi Polysaccharide Vaccine<br>* One dose of typhoid Vi polysaccharide vaccine.<br>Biological: Yellow Fever Vaccine<br>* One dose of yellow fever vaccine.<br>|
| Active Comparator: TF + YF + MenACWY-CRM197<br>Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine. | Biological: Typhoid Vi Polysaccharide Vaccine<br>* One dose of typhoid Vi polysaccharide vaccine.<br>Biological: Yellow Fever Vaccine<br>* One dose of yellow fever vaccine.<br>Biological: MenACWY-CRM Vaccine<br>* One dose of MenACWY-CRM vaccine.<br>|
| Active Comparator: JE + Rabies<br>Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies vaccine. | Biological: Japanese Encephalitis Vaccine<br>* Two doses of Japanese Encephalitis Vaccine.<br>Biological: Rabies Vaccine<br>* Three doses of Rabies vaccine.<br>|
| Active Comparator: JE + Rab + MenACWY-CRM197<br>Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine. | Biological: Japanese Encephalitis Vaccine<br>* Two doses of Japanese Encephalitis Vaccine.<br>Biological: Rabies Vaccine<br>* Three doses of Rabies vaccine.<br>Biological: MenACWY-CRM Vaccine<br>* One dose of MenACWY-CRM vaccine.<br>|
| Active Comparator: Rabies<br>Subjects ≥18 years to ≤60 years of age who received three doses of Rabies vaccine. | Biological: Rabies Vaccine<br>* Three doses of Rabies vaccine.<br>|
| Active Comparator: MenACWY-CRM197 (Combined)<br>Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine. | Biological: MenACWY-CRM Vaccine<br>* One dose of MenACWY-CRM vaccine.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Anti-typhoid Vi Antibody Concentrations | Assessment was made to demonstrate the non-inferiority of the geometric mean anti-typhoid Vi antibody concentrations, 28 days after the vaccination of typhoid Vi polysaccharide (TF) and yellow fever (YF) vaccines given concomitantly with MenACWY-CRM197 to typhoid Vi polysaccharide and yellow fever vaccines given alone in healthy adults aged ≥18 years to ≤60 years. | Baseline and 1 month postvaccination (day 29). | 
| Geometric Mean Anti-Yellow Fever Antibody Titer | Assessment was made to demonstrate the non-inferiority of the geometric mean anti-yellow fever antibody titers, 28 days after the vaccination of typhoid Vi polysaccharide (TF) and yellow fever (YF) vaccines given concomitantly with MenACWY-CRM197 to typhoid Vi polysaccharide and yellow fever vaccines given alone in healthy adults aged ≥18 years to ≤60 years. | Baseline and 1 month postvaccination (day 29). | 
| Geometric Mean Anti-Japanese Encephalitis Neutralizing Antibody Titers | Assessment was made to demonstrate the non-inferiority of the geometric mean anti-Japanese encephalitis neutralizing antibody titers, 28 days after the vaccination of the second dose of Japanese Encephalitis vaccine and third dose of the rabies virus vaccine given concomitantly with MenACWY-CRM197 or alone in healthy adults aged ≥18 years to ≤60 years. | Baseline and 1 month post last vaccination (day 57). | 
| Geometric Mean Anti-Rabies Virus Neutralizing Antibody Concentration | Assessment was made to demonstrate the non-inferiority of the geometric mean anti-rabies virus neutralizing antibody concentrations, 28 days after the vaccination of the second dose of Japanese encephalitis vaccine and third dose of rabies virus vaccine given concomitantly with MenACWY-CRM197 or alone in healthy adults aged ≥18 years to ≤60 years. | Baseline and 1 month post last vaccination (day 57). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages Of Subjects With Anti-YF Neutralizing Antibody Titers ≥ 1/10, 28 Days After The Vaccination Of Typhoid Vi Polysaccharide And Yellow Fever, Concomitantly With MenACWY-CRM197 Or Given Alone | Immunogenicity was assessed as the percentages of subjects who achieved seroprotection as measured by neutralization test for anti-YF neutralizing antibody titers after the vaccination of typhoid Vi polysaccharide and yellow fever, given alone or concomitantly with MenACWY-CRM197 on day 29. Seroprotection is defined as percentages of subjects who achieved anti-YF neutralizing antibody titers ≥ 1/10 on day 29. | Baseline and 1 month postvaccination (day 29). | 
| Percentages Of Subjects With Anti-JE Neutralizing Antibody Titers ≥ 1/10, 28 Days After The Vaccination Of The Last Doses Of Japanese Encephalitis And Rabies, Given Concomitantly With MenACWY-CRM197 Or Alone | Immunogenicity was measured as the percentages of subjects who achieved seroprotection as measured by neutralization test for anti-Japanese encephalitis neutralizing antibody titers, 28 days after administration of the second dose of Japanese encephalitis virus vaccine and 28 days after the vaccination of third dose of rabies virus vaccine, given alone or concomitantly with MenACWY-CRM197. Seroprotection is defined as percentages of subjects who achieved anti-JE neutralizing titers ≥ 1/10 on Day 57. | Baseline and 1 month post last vaccination (day 57). | 
| Percentages Of Subjects With Anti-Rabies Virus Antibody Concentrations ≥ 0.5 IU/mL 28 Days After the Vaccination Of The Last Doses Of Japanese Encephalitis And Rabies Virus, Given Concomitantly With MenACWY-CRM197 Or Alone | Immunogenicity was assessed as the percentages of subjects who achieved seroprotection as measured by neutralization test for anti-rabies neutralizing antibody titers, 28 days after administration of the second dose of Japanese encephalitis virus vaccine and 28 days after the vaccination of third dose of rabies virus vaccine, given alone or concomitantly with MenACWY-CRM197. Seroprotection is defined as a subject with a baseline hSBA titer < 1:4, seroresponse was defined as a post-vaccination hSBA titer ≥ 1:8; for a subject with a baseline hSBA titer ≥ 1:4, seroresponse was defined as a post-vaccination hSBA titer of at least 4 times the baseline. | Baseline and 1 month post last vaccination (day 57). | 
| Geometric Mean hSBA Titers For Meningococcal Serogroups A,C,W,Y 28 Days After The Vaccination Of MenACWY-CRM197 Given Concomitantly With Typhoid Vi Polysaccharide And Yellow Fever Vaccines Alone | Immunogenicity was assessed by Serum Bactericidal Assay using human complement (hSBA) geometric mean titers (GMTs) for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with typhoid Vi polysaccharide and yellow fever vaccines or alone. | Baseline and 1 month postvaccination (day 29). | 
| Seroresponse Rate For Meningococcal Serogroups A,C,W,Y 28 Days After Vaccination of MenACWY-CRM197 Given Concomitantly With Typhoid Vi Polysaccharide and Yellow Fever Vaccines or Alone | Immunogenicity was assessed by seroresponse rates as measured by human serum bactericidal activity (hSBA) titers for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with typhoid Vi polysaccharide and yellow fever vaccines or alone. 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 four times the baseline. | 1 month postvaccination (day 29) | 
| Geometric Mean hSBA Titers for Meningococcal Serogroups A,C,W,Y 28 Days After the Vaccination of MenACWY-CRM197 Given Concomitantly With Japanese Encephalitis and Rabies Virus Vaccines or Alone | Immunogenicity was measured by human serum bactericidal activity (hSBA) geometric mean titers (GMTs) for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with Japanese encephalitis and rabies virus vaccines or alone. | Baseline and 1 month post last vaccination (day 29 or day 57). | 
| Seroresponse Rate for Meningococcal Serogroups A,C,W,Y 28 Days After Vaccination of MenACWY-CRM197 Given Concomitantly With Japanese Encephalitis and Rabies Virus Vaccines or Alone | Immunogenicity was assessed by seroresponse rates as measured by human serum bactericidal activity (hSBA) titers for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with Japanese encephalitis and rabies virus vaccines or alone. Seroresponse is defined as a subject with a baseline hSBA titer < 1:4, seroresponse was defined as a post-vaccination hSBA titer ≥ 1:8; for a subject with a baseline hSBA titer ≥ 1:4, seroresponse was defined as a postvaccination hSBA titer of at least 4 times the baseline. | 1 month post last vaccination (day 29 or day 57) | 
| Geometric Mean Rabies Virus Neutralizing Antibody Concentration 28 Days After the Last Vaccination Of Rabies Virus Vaccine Concomitantly Either With Japanese Encephalitis or With Japanese Encephalitis And MenACWY-CRM197 | The immunogenicity was assessed in rabies virus vaccine as measured by geometric mean rabies virus neutralizing antibody concentration, 28 days after vaccination of the third dose, when administered alone or concomitantly either with Japanese encephalitis vaccine or with Japanese Encephalitis and MenACWY-CRM197 vaccines. | Baseline and 1 month post last vaccination (day 57). | 
| Percentages of Subjects With Anti-rabies Virus Concentrations ≥ 0.5 IU/mL, 28 Days After the Last Vaccination of Rabies Virus Vaccine Concomitantly Either With Japanese Encephalitis or With Japanese Encephalitis and MenACWY-CRM197 | Immunogenicity was measured as the percentages of subjects who achieved seroprotection of anti-rabies virus antibody concentrations 28 days after vaccination of the third dose of rabies virus vaccine, when administered alone or concomitantly either with Japanese encephalitis or with Japanese encephalitis and MenACWY-CRM197 vaccines. Seroprotection is defined as percentages of subjects who achieved anti-rabies virus antibody concentrations ≥ 0.5 IU/mL on day 57. | Baseline and 1 month post last vaccination (day 57). | 
| Number of Subjects With Adverse Events of Special Interest After Any Vaccination of Japanese Encephalitis and Rabies Virus Vaccines Given Concomitantly With MenACWY-CRM197 or Alone | In addition to the AEs and SAEs. Additional AESI were collected from day 1 to day 57 postvaccination in subjects after the vaccination of Japanese encephalitis and rabies virus vaccines given concomitantly with MenACWY-CRM197 or alone. | day 1 to day 57 post last vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adults, international travel vaccination, Meningococcal disease, meningococcal meningitis, typhoid, yellow fever, rabies, Japanese encephalitis