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

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

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

Conditions
-----------------
Meningococcal Disease

Intervention / Treatment
-----------------
* Biological: rMenB+OMV NZ


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 23 Months
Maximum Age: 27 Months

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B246_12_M12<br>Subjects assessed one year post administration of rMenB+OMV NZ and MMRV at 12th month after primary vaccination at 2nd ,4th and 6th months of age. | Biological: rMenB+OMV NZ<br>* 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.<br>|
| Experimental: B246_12M13<br>Subjects assessed one year post administration of rMenB+OMV NZ at 12th month and MMRV at 13th month after primary vaccination at 2nd ,4th and 6th months of age. | Biological: rMenB+OMV NZ<br>* 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.<br>|
| Experimental: B13_15_27<br>Subjects assessed at 12 months after two catch-up doses of rMenB+OMV NZ administered to children at 13th and 15th months of age and MMRV at 12th month; at 1 month and 6 months post booster dose administered at 27 months of age. | Biological: rMenB+OMV NZ<br>* 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.<br>|
| Experimental: B12_14_26<br>Subjects assessed at 12 months after two catch-up doses of rMenB+OMV NZ administered to children at either 12th and 14th months of age and MMRV at 12th month; at 1 month and 6 months post booster dose administered at 26 months of age. | Biological: rMenB+OMV NZ<br>* 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.<br>|
| Experimental: B_24_26<br>Subjects assessed at 1 month and 6 months post two catch-up doses of rMenB+OMV NZ administered to naive children at 24 and 26 months of age. | Biological: rMenB+OMV NZ<br>* 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.<br>|
| Experimental: B12M13<br>Subject was randomized in group B13_15_27 but treated as group B12_M13. | Biological: rMenB+OMV NZ<br>* 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.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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 | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Children, Meningococcal disease, Prevention, Vaccination