One Year Antibody Persistence After a Fourth Dose Boost or Two Catch-Up Doses of Novartis Meningococcal B Recombinant Vaccine Administered Starting From 12 Months of Age and Response to a Third Dose Boost or Two Catch-Up Doses Starting at 24 Months of Age

Meningococcal Disease Clinical Trial

Official title:

A Phase 3, Open-Label, Multi-Center, Extension Study of V72P13E1 to Assess Antibody Persistence at One Year After a Fourth Dose Boost or Two Catch-Up Doses of Novartis Meningococcal B Recombinant Vaccine Administered Starting at 12 Months of Age and to Evaluate the Response to a Third Dose Boost or Two Catch-Up Doses Starting at 24 Months of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01139021
• Other study ID #: V72P13E2
• Secondary ID: EudraCT No 2009-
• Status: Completed
• Phase: Phase 3
• First received: June 4, 2010
• Last updated: April 9, 2015
• Start date: June 2010
• Est. completion date: September 2011

Study information

• Verified date: April 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines AgencyUnited States: Food and Drug AdministrationEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

One year antibody persistence after the fourth dose boost or two catch-up doses administered starting from 12 months of age and to evaluate the response to a a third dose boost or two catch-up dose starting at 24 months of age.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 508
• Est. completion date: September 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 23 Months to 27 Months

Eligibility

Inclusion Criteria:

• Healthy male and female children, 23 to 27 months of age (naïve children)

• Available for all the visits scheduled in the study;

• For whom parent(s)/legal guardian(s) have given written informed consent according to local regulations after the nature of the study has been explained;

• Available for all the visits scheduled in the study;

• In good health as determined by medical history, physical examination, clinical judgment of the investigator.

• Healthy children who participated in the immunogenicity part of V72P13E1 and have received their last vaccination 12 months (-30/+60 days) before enrolment in V72P13E2;

• Who received all vaccinations with rMenB+OMV NZ in V72P13 and V72P13E1 according to the protocols;

• Who provided at least the blood sample one month after their fourth dose of rMenB+OMV NZ (groups B246_12M12/B246_12M13) or after their second dose of rMenB+OMV NZ (groups B13_15_27/B12_14_26) in V72P13E1 according to the protocol;

• For whom parent(s)/legal guardian(s) had given written informed consent after the nature of the study has been explained;

• In good health as determined by medical history, physical examination, clinical judgment of the investigator.

Exclusion Criteria:

• Subjects whose parent(s)/legal guardian(s) were unwilling or unable to give written informed consent to participate in the study;

• History of any meningococcal B vaccine administration;

• Previous ascertained or suspected disease caused by N. meningitidis;

• For whom parent(s)/legal guardian(s) have given written informed consent according to local regulations after the nature of the study has been explained;

• History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;

• Antibiotics treatment within 6 days prior to enrolment;

• Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;

• Any serious chronic or progressive disease

• Known or suspected impairment/ alteration of the immune system,

• Receipt of, or intent to immunize with another vaccine, within 30 days prior and after vaccination with the investigational vaccines (within 14 days for licensed flu vaccines)

• Significant acute or chronic infection within the previous 7 days or axillary temperature =38C within the previous day;

• Family members and household members of research staff;

• Any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, diabetes mellitus Type I, cardiac disease, hepatic disease, neurological disease or seizure, either associated with fever or as part of an underlying neurological disorder or syndrome, autoimmune disease, Human Immunodeficiency Virus (HIV) infection or Acquired Immune Deficiency Syndrome (AIDS), or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition);

• Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within 30 days prior to enrolment (use of low or moderate doses of inhaled steroids is not an exclusion);

• Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 90 days prior to enrolment;

• Participation in another clinical trial within 90 days prior to enrolment or planned for during study;

• Receipt of, or intent to immunize with any other vaccine(s) within 30 days prior to enrolment (exception: flu-vaccines should not be administered within 14 days prior to enrolment);

• Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Meningococcal Disease
• Meningococcal Infections

Intervention

Biological:
• rMenB+OMV NZ
Subjects will be assigned to a study group based on the group assignment in the parent study (follow-on subjects). In addition, one group of naïve age-matched subjects will be recruited at the same study sites. Subjects who had received 4 doses of rMenB+OMV NZ will have one visit including one blood draw. Subjects who had received two catch-up doses in V72P13E1 will receive a third dose boost and will have 3 blood samples drawn. Naïve subjects will receive two catch-up doses and have 3 blood samples drawn.

Locations

Country	Name	City	State
Czech Republic	amostatná ordinace praktického lékare pro deti a dorost Jindrichuv Hradec	Hradec
Czech Republic	Detské oddelení nemocnice Náchod	Náchod
Czech Republic	Detské oddelení nemocnice Pardubice	Pardubice
Finland	University of Tampere Medical School, Vaccine Research Center Tampere	Biokatu 10	Tampere
Finland	Espoo Vaccine Research Clinic,	Espoo
Finland	Helsinki East, Vaccine Research Clinic,	Helsinki
Finland	Helsinki South, Vaccine Research Clinic,	Helsinki
Finland	Järvenpää, Vaccine Research Clinic	Järvenpää
Finland	Kokkola Vaccine Research Clinic	Kokkola
Finland	Kotka Vaccine Research Clinic	Kotka
Finland	Kuopio Vaccine Research Clinic	Kuopio
Finland	Lahti Vaccine Research Clinic	Lahti
Finland	Oulu Vaccine Research Clinic	Oulu
Finland	Pori Vaccine Research Clinic	Pori
Finland	Seinäjoki Vaccine Research Clinic	Seinäjoki
Finland	Tampere Vaccine Research Clinic	Tampere
Finland	Turku Vaccine Research Clinic	Turku
Finland	Vantaa East, Vaccine Research Clinic	Vantaa
Finland	Vantaa West, Vaccine Research Clinic	Vantaa

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Czech Republic,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Titers (GMTs) to Assess Antibody Persistence at 12 Months After a Booster Dose of rMenB+OMV NZ Vaccination.	To assess the immunogenicity in terms of human Serum Bactericidal Assay (hSBA) GMTs through antibody persistence at 12 months after a booster (fourth) dose of Novartis Meningococcal B Recombinant Vaccine (rMenB+OMV NZ) in groups that received a three-dose primary series at 2, 4,6 months of age. Group B246_12M12 received Measles, Mumps, Rubella, Varicella (MMRV) at 12 months of age (concomitantly) and group B246_12M13 received MMRV at 13 months of age (separately).; Analysis was done on Modified Intention-To-Treat (MITT) population- (Primary).	12 months post booster (fourth) vaccination.	No
Primary	Percentage of Subjects With hSBA =1:5 and hSBA =1:8 to Assess Antibody Persistence at on 12 Months After a Booster Dose of rMenB+OMV NZ Vaccination.	To assess the immunogenicity in terms of percentage of subjects with hSBA =1:5 and hSBA =1:8 through antibody persistence at 12 months after a booster (fourth) dose of rMenB+OMV NZ in groups that received a three-dose primary series at 2, 4, 6 months of age. Group B246_12M12 received MMRV at 12 months of age (concomitantly) and group B246_12M13 received MMRV at 13 months of age (separately).; Analysis was done on MITT population (Primary).	12 months post booster (fourth) vaccination.	No
Primary	Geometric Mean Concentrations (GMCs) to Assess Antibody Persistence at One Year After a Booster Dose of rMenB+OMV NZ Vaccination.	To assess the immunogenicity in terms of GMCs determined by Enzyme Linked Immunosorbent Assay (ELISA) through antibody persistence at one year after a booster (fourth) dose of rMenB+OMV NZ in groups that received a three-dose primary series at 2, 4, 6 months of age. Group B246_12M12 received MMRV at 12 months of age (concomitantly) and group B246_12M13 received MMRV at 13 months of age (separately) against vaccine antigen 287-953.; Analysis was done on MITT population (Primary).	12 months post booster (fourth) vaccination.	No
Secondary	GMTs to Assess Antibody Persistence at 12 Months After Two Catch-up Doses and 6 Months After Booster Dose of rMenB+OMV NZ Vaccination.	To assess the immunogenicity in terms of hSBA GMTs at 12 months after two catch up doses previously administered to children at either 12 and 14 or 13 and 15 months of age and 6 months after a booster dose of rMenB+OMV NZ administered at 26 or 27 months of age.; Both the groups received MMRV at 12 months of age.	12 months post two catch-up dose vaccination and 6 months post booster dose.	No
Secondary	Percentage of Subjects With hSBA =1:5 and hSBA =1:8 to Assess Antibody Persistence at 12 Months After Two Catch up Doses and 6 Months After a Booster Doses of rMenB+OMV NZ Vaccination.	To assess the immunogenicity in terms of percentage of subjects with hSBA =1:5 and hSBA =1:8 at 12 months after two catch up doses previously administered to children at either 12 and 14 or 13 and 15 months of age and 6 months after a booster dose of rMenB+OMV NZ administered at 26 or 27 months of age.; Both the groups received MMRV at 12 months of age.	6month post booster dose and 12 months post two catch-up dose vaccination.	No
Secondary	Percentage of Subjects With at Least Four Fold Increase in hSBA Titers to Evaluate Antibody Response 1 Month Post Booster Dose of rMenB+OMV NZ Vaccination.	To assess the immunogenicity in terms of percentage of subjects with at least four fold increase in hSBA titers 1 month post booster dose of rMenB+OMV NZ administered at 26 or 27 months of age, in children previously administered two catch-up doses of rMenB+OMV NZ at either 12 and 14 or 13 and 15 months of age.Both the groups received MMRV at 12 months of age.	1 month post booster dose versus prebooster.	No
Secondary	GMCs to Assess Antibody Persistence at One Year After Two Catch-up Doses and 6 Months After Booster of rMenB+OMV NZ Vaccination Against 287-953 Strain.	To assess the immunogenicity in terms of GMCs determined by ELISA at 12 months after two catch up doses previously administered to children at either 12 and 14 or 13 and 15 months of age and 6 months after a booster dose of rMenB+OMV NZ administered at 26 or 27 months of age.; Both the groups received MMRV at 12 months of age.	12 months post two catch-up dose vaccination and 6 months post booster dose.	No
Secondary	GMTs to Characterize Antibody Response at 1 Month and 6 Month Post Two Catch-up Doses of rMenB+OMV NZ Administered to Naive Children at 24 and 26 Months of Age.	To assess the immunogenicity in terms of GMTs through antibody response at 1 month and 6 month post two catch-up doses of rMenB+OMV NZ administered to naive children at 24 and 26 months of age.	1 month and 6 months post two catch-up doses.	No
Secondary	Percentage of Subjects With hSBA =1:5 and hSBA =1:8 to Assess Antibody Response at 1 Month and 6 Month Post Two Catch-up Doses of rMenB+OMV NZ Administered to Naive Children at 24 and 26 Months of Age.	To assess the immunogenicity in terms of percentage of subjects with hSBA =1:5 and hSBA =1:8 through antibody response at at 1 month and 6 month post two catch-up doses of rMenB+OMV NZ administered to naive children at 24 and 26 months of age.	1 month and 6 months post two catch-up doses.	No
Secondary	Percentage of Subjects With Four Fold Increase in hSBA to Assess Antibody Response at 1 Month Post Two Catch-up Doses of rMenB+OMV NZ Administered to Naive Children at 24 and 26 Months of Age.	To assess the immunogenicity in terms of percentage of subjects with fourfold increases in hSBA titers at 1 month post two catch-up doses of rMenB+OMV NZ in children previously administered to naive children at 24 and 26 months of age against 4 strains.; Analysis was done on MITT population (Secondary).	1 month post two catch-up doses versus prevaccination	No
Secondary	GMCs to Assess Antibody Response at 1 Month and 6 Month Post Two Catch-up Doses of rMenB+OMV NZ Administered to Naive Children at 24 and 26 Months of Age Against 287-953 Strain.	To assess the immunogenicity in terms of GMCs to assess through antibody response at 1 month and 6 month post two catch-up doses of rMenB+OMV NZ administered to naive children at 24 and 26 months of age against 287-953 strain.; Analysis was done on MITT population (Secondary).	1 month and 6 months post two catch-up doses.	No
Secondary	Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) After Receiving a Booster (Third) Dose of rMenB+OMV NZ Administered at One Year After Two Catch-up Doses of rMenB+OMV NZ, Previously Administered to Children.	To assess the safety and tolerability by reporting solicited local and systemic AEs of a booster (third) dose of rMenB+OMV NZ administered at one year after two catch-up doses of rMenB+OMV NZ, previously administered to children at either 12 and 14 or 13 and 15 months of age in study V72P13E1.	Up to 7 days after any vaccination.	Yes
Secondary	Number of Subjects Reporting Unsolicited Adverse Events After Receiving a Booster (3rd) Dose of rMenB+OMV NZ Administered at One Year After Two Catch-up Doses of rMenB+OMV NZ, Previously Administered to Children.	To assess the safety and tolerability in terms of number of subjects reporting unsolicited adverse events in yerms of serious adverse events (SAEs), atleast possibly related SAEs and AEs leading to withdrawl of a booster (third) dose of rMenB+OMV NZ administered at one year after two catch-up doses of rMenB+OMV NZ, previously administered to children at either 12 and 14 or 13 and 15 months of age in study V72P13E1.	Up to 7 days after any vaccination.	Yes
Secondary	Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Two Catch-up Doses of rMenB+OMV NZ Administered to Naive Children at 24 and 26 Months of Age.	To assess the safety and tolerability by reporting solicited local and systemic adverse events of two catch-up doses of rMenB+OMV NZ administered to naive children at 24 and 26 months of age.	Up to 7 days after any vaccination.	Yes
Secondary	Number of Subjects Reporting Unsolicited Adverse Events After Receiving Two Catch-up Doses of rMenB+OMV NZ Administered to Naive Children at 24 and 26 Months of Age.	To assess the safety and tolerability in terms of number of subjects reporting unsolicited adverse events after receiving two catch-up doses of rMenB+OMV NZ administered to naive children at 24 and 26 months of age. The analysis was done on safety subset.	Up to 7 days after any vaccination	Yes