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

Meningococcal Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01466387
• Other study ID #: V59_38
• Secondary ID: 2011-000475-14
• Status: Completed
• Phase: Phase 3
• First received: November 3, 2011
• Last updated: February 7, 2014
• Start date: November 2011
• Est. completion date: April 2012

Study information

• Verified date: February 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compares the safety and immunogenicity profile of several travel vaccines given alone or concomitantly with MenACWY-CRM to healthy adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 552
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

Female and male subjects who must be healthy and must be:

1. Between 18 and 60 years of age inclusive and who have 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, having a negative urine pregnancy test.

Exclusion Criteria:

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

1. who are breastfeeding;

2. 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);

3. who have been immunized with any of the study vaccines within the last five years as determined by medical history and/or vaccination card;

4. 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;

5. 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);

6. who have received an anti-malaria drug, up to 2 months prior to the study;

7. 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;

8. 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);

9. who have epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome;

10. 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;

11. 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;

12. who are known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;

13. who have myasthenia gravis; thyroid or thymic disorders,

14. who have any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives;

15. who are part of the study personnel or close family members of those conducting this study.

16. for whom a long-term stay (= 1 month) was planned in Africa, Latin America, or Asia.

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Japanese
• Japanese Encephalitis
• Meningitis
• Meningitis, Meningococcal
• Meningococcal Disease
• Meningococcal Infections
• Meningococcal Meningitis
• Rabies
• Typhoid
• Typhoid Fever
• Yellow Fever

Intervention

Biological:
• Typhoid Vi Polysaccharide Vaccine
One dose of typhoid Vi polysaccharide vaccine.
• Yellow Fever Vaccine
One dose of yellow fever vaccine.
• Japanese Encephalitis Vaccine
Two doses of Japanese Encephalitis Vaccine.
• Rabies Vaccine
Three doses of Rabies vaccine.
• MenACWY-CRM Vaccine
One dose of MenACWY-CRM vaccine.

Locations

Country	Name	City	State
Czech Republic	Centrum ockovani a cestovni mediciny (Vaccination and Travel Medicine Centre) Poliklinika II	Bratri Stefanu 895	Hradec Kralove
Germany	Berliner Centrum Fur Reise und Tropenmedizin	Jaegerstrasse 67-69	Berlin
Germany	University of Munich Georgenstr.5	Muenchen
Germany	Universitat Rostock, Ernst Heydemann Str 6	Rostock

Sponsors (2)

Lead Sponsor	Collaborator
Novartis	Novartis Vaccines

Countries where clinical trial is conducted

Czech Republic,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).
Primary	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).
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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)
Secondary	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).
Secondary	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)
Secondary	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).
Secondary	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).
Secondary	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