Clinical trial NCT01717638: Persistence of Antibody Levels and Response to Fifth or Third Meningococcal B Recombinant Vaccine in 4-year Old Healthy Children Who Previously Participated in Study V72P12E1
Official title: A Phase 3, Open Label, Multi-Center, Extension Study to Assess Antibody Persistence and Response to a Third or Fifth Dose of Novartis Meningococcal B Recombinant Vaccine in 4-Year-Old Children Who Previously Participated in Study V72P12E1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningococcal Disease
Meningococcal Meningitis
Keywords: Meningococcal disease, vaccines, children, persistence
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-10-30
Enrollment: 805
Sex: ALL
Minimum age (years): 48
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: It is a Phase 3 extension of study V72P12E1 (NCT00944034). The main aim of the second extension study is to explore the bactericidal antibody persistence in 4-year-old children after a fourth dose boost of rMenB+OMV NZ or after a two-dose catch-up schedule of rMenB+OMV NZ administered to toddlers as part of their respective vaccination courses in study V72P12E1.

In addition, this study will characterize the antibody response to a fifth dose boost in all children who received a three-dose primary series of rMenB+OMV NZ at 2, 3, 4 months of age (in parent study V72P12, NCT00721396), and only in a subset of children who received a three-dose primary series of rMenB+OMV NZ at 2, 4, 6 months of age (in parent study V72P12). Antibody response will also be characterized to a third dose boost of rMenB+OMV NZ administered at approximately 4 years of age in all children who received a two catch-up doses of rMenB+OMV NZ as toddlers in study V72P12E1.

Finally, the safety and immunogenicity of two catch-up doses of rMenB+OMV NZ administered 2 months apart to healthy naïve children at 4 years of age will be assessed.


Eligibility criteria: Inclusion Criteria:

A. Inclusion Criteria for naïve subjects, newly enrolled (B48_50):

1. 4 years old (48 to 60 months) healthy male and female subjects will be recruited from the same sites as in study V72P12E1. The age window is defined as the first day the subject turns 4 years old up to the day before the subject turns 5 years old.
2. For whom parent/legal guardian(s) has given written informed consent after the nature of the study has been explained.
3. For whom parent/legal guardian(s) confirmed availability for the visit(s) scheduled in the study.
4. In good health as determined by medical history, physical examination, clinical judgment of the investigator.

B. Inclusion Criteria for follow-on participants (Groups B+R246 12_48, B+R246 18_48, B+R246 24_48, B246 12_48, B246 18_48, B246 24_48, B+R234 12_48, B+R234 18_48, B+R234 24_48, B12 14_48, B18 20_48, B24 26_48):

Inclusion criteria are the same as for Group B48_50, with the addition that they are subjects who completed the vaccination course of V72P12E1 study.

Exclusion Criteria:

A. Exclusion Criteria for naïve subjects, newly enrolled (Group 7):

1. Subjects whose parents/legal guardians are unwilling or unable to give written informed consent to participate in the study.
2. History of any meningococcal B vaccine administration.
3. Previous ascertained or suspected disease caused by N. meningitidis.
4. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis.
5. History of allergic reaction to any vaccine component.
6. Significant chronic infection.
7. Any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, diabetes mellitus Type I, cardiac disease, hepatic disease, progressive neurological disease or seizure, either associated with fever or as part of an underlying neurological disorder or syndrome, autoimmune disease, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition).
8. Known or suspected impairment/alteration of the immune system resulting from (for example) receipt of chronic immunosuppressive therapy or immunostimulants.
9. Participation in another clinical trial within 90 days prior to enrolment or planned for during study.
10. Family members and household members of research staff.
11. Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

B. Exclusion Criteria for follow-on participants ((Groups B+R246 12_48, B+R246 18_48, B+R246 24_48, B246 12_48, B246 18_48, B246 24_48, B+R234 12_48, B+R234 18_48, B+R234 24_48, B12 14_48, B18 20_48, B24 26_48):

Exclusion criteria are the same as for Group B48_50, with the exception of criterion 2 and excluding participation in V72P12E1 for criterion 9.

Primary outcomes:
measure: Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules
timeFrame: Day 1 (24-36 months post booster; baseline for naive)
measure: Persisting Antibody Titers in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules
timeFrame: Day 1 (24-36 months post booster; baseline for naive)
measure: Geometric Mean Ratios (GMRs) in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules
timeFrame: Day 1 (24-36 months post booster dose; baseline for naive)
Secondary outcomes:
measure: Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Two Catch up Doses of rMenB+OMV NZ Vaccine According to Different Schedules
timeFrame: Day 1 (22-34 months post last MenB vaccine)
measure: Persisting Antibody Titers in Children (at 4 Years of Age) Who Had Previously Received Two Catch up Doses of rMenB+OMV NZ Vaccine According to Different Schedules
timeFrame: Day 1 (22-36 months post last MenB vaccine; baseline for naive)
measure: GMRs of GMTs in Children (at 4 Years of Age) Who Had Previously Received Two Catch up Doses of rMenB+OMV NZ Vaccine According to Different Schedules
timeFrame: Day 1 (22-34 months post last MenB vaccine)
measure: Percentages of Subjects With Serum Bactericidal Titers ≥1:5 and ≥1:8 After a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules
timeFrame: Day 31 (1 month post vaccination)
measure: GMTs in Children Following a Fifth Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules
timeFrame: Day 31 (1 month post vaccination)
measure: Geometric Mean Ratios of GMTs in Subjects Following a Fifth Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age), Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules
timeFrame: Day 31 (1 month post vaccination)
measure: Percentages of Subjects With Fourfold Increase in hSBA Titers After Receiving a Fifth Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age), Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules
timeFrame: Day 31 (1 month post vaccination)
measure: Percentages of Subjects With hSBA Titers ≥1:5 and ≥1:8 Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age), Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules
timeFrame: Day 31 (1 month post vaccination)
measure: GMTs Following a Third Dose of rMenB+OMV NZ Vaccine in Children (at 4 Years of Age) Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules
timeFrame: Day 31 (1 month post vaccination)
measure: GMRs of GMTs in Children Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules.
timeFrame: Day 31 (1 month post vaccination)
measure: Percentages of Subjects With a 4-fold Increase in hSBA Titers Following a Third Dose of rMenB+OMV NZ Vaccine Given at 4 Years of Age to Children Who Previously Received 2 Catch up Doses of the Same Vaccine
timeFrame: Day 31 (1 month post vaccination)
measure: Percentages of Subjects With hSBA ≥1:5 and ≥1:8 in Response of Two Catch up Doses of rMenB+OMV NZ Vaccine When Administered to Children at 4 Years of Age.
timeFrame: Day 91 (1 month post second vaccination)
measure: GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age
timeFrame: Day 91 (1 month post second vaccination)
measure: GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age
timeFrame: Day 91 (1 month post second vaccination)
measure: Percentages of Subjects With 4-fold Increase in Serum Bactericidal Titers, Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age
timeFrame: Day 91 (1 month post second vaccination)
measure: Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)
timeFrame: From day 1 to day 7 after vaccination
measure: Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)
timeFrame: From day 1 to day 7 after vaccination
measure: Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age
timeFrame: From day 1 to day 7 after any vaccination
measure: Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)
timeFrame: From day 1 to study termination
measure: Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)
timeFrame: From day 1 to study termination
measure: Number of Subjects Reporting Unsolicited AEs After Any Vaccination.
timeFrame: From day 1 to study termination
Other outcomes:
Locations:
city: Jaromer
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Alšova 466
city: Jaromer
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Dr. E.Beneše 191
city: Sezemice
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Havlickova 168
city: Hronov
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Hostovského 485
city: Ceska Skalice
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Husovo namesti 36
city: Pardubice
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: L.Male 656
city: Hradec Králové
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Manesova 646
city: Hronov
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Palackeho 517
city: Hradec Králové
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Pardubicka 752
city: Chlumec nad Cidlinou
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Pernstynska 127/I
city: Nachod
country: Czech Republic
facility: Nemocnice Náchod
state: Purkynova 446
city: Jindrichuv Hradec
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Ruských legií 352
city: Pardubice
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Sladkovskeho 2617
city: Jindrichuv Hradec
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: Sídliste Vajgar 724/III
city: Hradec Kralove
country: Czech Republic
facility: Fakulta vojenskeho zdravotnictvi UO
state: Trebesska 1575
city: Holice
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: U kaplicky 1042
city: Jindrichuv Hradec
country: Czech Republic
facility: Ordinace praktickeho lekare pro deti a dorost
state: U nemocnice380/III
city: Florence
country: Italy
facility: Universita di Firenze -Pediatria
city: Milan
country: Italy
facility: IRCCS Cà Granda
city: Novara
country: Italy
facility: Ospedale Maggiore della Carita
city: Padova
country: Italy
facility: Dip Pediatria AO Padova
city: Santiago de Compostela A Coruña
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valencia
country: Spain
facility: Centro Superior de Investigacion en Salud Publica/Clinica Universitaria San Vicente Martir
city: Vigo Pontevedra
country: Spain
facility: Complexo Hospitalario Xeral Cies
city: Oxford
country: United Kingdom
facility: Oxford Vaccine Group - Centre for Clinical Vaccinology and Tropical Medicine Churchill Hospital
state: Headington
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust
city: London
country: United Kingdom
facility: St Georges Hospital
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
References:
citation: Sadarangani M, Sell T, Iro MA, Snape MD, Voysey M, Finn A, Heath PT, Bona G, Esposito S, Diez-Domingo J, Prymula R, Odueyungbo A, Toneatto D, Pollard AJ; European MenB Vaccine Study Group. Persistence of immunity after vaccination with a capsular group B meningococcal vaccine in 3 different toddler schedules. CMAJ. 2017 Oct 16;189(41):E1276-E1285. doi: 10.1503/cmaj.161288.