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

Meningococcal Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01717638
• Other study ID #: V72P12E2
• Secondary ID: 2011-004931-30
• Status: Completed
• Phase: Phase 3
• First received: October 18, 2012
• Last updated: December 29, 2014
• Start date: November 2012
• Est. completion date: October 2013

Study information

• Verified date: December 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyCzech Republic: State Institute for Drug ControlSpain: Agencia Española de Medicamentos y Productos SanitariosItaly: Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 805
• Est. completion date: October 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 48 Months to 60 Months

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Meningitis, Meningococcal
• Meningococcal Disease
• Meningococcal Infections
• Meningococcal Meningitis

Intervention

Biological:
• 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine
0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose
• 2 doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine
0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, two doses, two months apart

Locations

Country	Name	City	State
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Ceska Skalice	Husovo namesti 36
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Chlumec nad Cidlinou	Pernstynska 127/I
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Holice	U kaplicky 1042
Czech Republic	Fakulta vojenskeho zdravotnictvi UO	Hradec Kralove	Trebesska 1575
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Hradec Králové	Manesova 646
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Hradec Králové	Pardubicka 752
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Hronov	Hostovského 485
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Hronov	Palackeho 517
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Jaromer	Alšova 466
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Jaromer	Dr. E.Beneše 191
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Jindrichuv Hradec	U nemocnice380/III
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Jindrichuv Hradec	Sídliste Vajgar 724/III
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Jindrichuv Hradec	Ruských legií 352
Czech Republic	Nemocnice Náchod	Nachod	Purkynova 446
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Pardubice	Sladkovskeho 2617
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Pardubice	L.Male 656
Czech Republic	Ordinace praktickeho lekare pro deti a dorost	Sezemice	Havlickova 168
Italy	Universita di Firenze -Pediatria	Florence
Italy	IRCCS Cà Granda	Milan
Italy	Ospedale Maggiore della Carita	Novara
Italy	Dip Pediatria AO Padova	Padova
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago de Compostela A Coruña
Spain	Centro Superior de Investigacion en Salud Publica/Clinica Universitaria San Vicente Martir	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Complexo Hospitalario Xeral Cies	Vigo Pontevedra
United Kingdom	North Bristol NHS Trust	Bristol
United Kingdom	Royal Devon and Exeter NHS Foundation Trust	Exeter
United Kingdom	St Georges Hospital	London
United Kingdom	Oxford Vaccine Group - Centre for Clinical Vaccinology and Tropical Medicine Churchill Hospital	Oxford	Headington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Czech Republic,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The antibody persistence at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the response in naïve children and reported as percentages of subjects with human serum bactericidal assay (hSBA) titers =1:5 and =1:8.; The functional bactericidal antibodies directed against serogroup B meningococci were assessed using the Serum Bactericidal Assay (SBA) using human serum as the source of exogenous complement (hSBA).	Day 1 (24-36 months post booster; baseline for naive)	No
Primary	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	The persisting antibody titers at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the titers in naive children and reported as geometric mean titers (GMTs).	Day 1 (24-36 months post booster; baseline for naive)	No
Primary	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	The GMRs of GMTs (48 months/one month post booster vaccination) at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is reported.	Day 1 (24-36 months post booster dose; baseline for naive)	No
Secondary	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	The antibody persistence in children at 4 year of age, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) according to different schedules is reported as percentages of subjects with hSBA titers =1:5 and hSBA titers =1:8.	Day 1 (22-34 months post last MenB vaccine)	No
Secondary	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	The persisting GMTs in children at 4 years of age, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules are reported.	Day 1 (22-36 months post last MenB vaccine; baseline for naive)	No
Secondary	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	The GMRs of GMTs (48 months/one month post last vaccination) in children at 4 years of age who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules.	Day 1 (22-34 months post last MenB vaccine)	No
Secondary	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	The Percentages of subjects with hSBA titers =1:5 and =1:8, one month after a 5th dose of rMenB+OMV NZ vaccine was given children who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of the same vaccine according to different schedules is compared with the hSBA response of children who received first dose of rMenB+OMV NZ at 4 years of age.	Day 31 (1 month post vaccination)	No
Secondary	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	The GMTs, at one month after a 5th dose of rMenB+OMV NZ vaccine in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules, are compared with the GMTs of children who received first dose of rMenB+OMV NZ at 4 years of age.	Day 31 (1 month post vaccination)	No
Secondary	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	The GMRs of GMTs (one month post booster/48 months persistence), one month after a 5th dose of rMenB+OMV NZ vaccine was given children, who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the GMR (one month post 1 dose\baseline) of children who received first dose of rMenB+OMV NZ at 4 years of age.	Day 31 (1 month post vaccination)	No
Secondary	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	The fourfold increase in hSBA titers, one month after a 5th dose of rMenB+OMV NZ vaccine was given to children, who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) and a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the response in children who received the first dose of rMenB+OMV NZ vaccine at 4 years of age.	Day 31 (1 month post vaccination)	No
Secondary	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	The percentages of subjects with hSBA titers =1:5 and hSBA titers =1:8 at one month after a third dose of rMenB+OMV NZ vaccine was given to children, who had previously received 2 catch up doses (at 12,14 or 18,20 or 24,26 months) of the same vaccine according to different schedules, are reported.	Day 31 (1 month post vaccination)	No
Secondary	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	The GMTs, one month following a third dose of rMenB+OMV NZ vaccine in 4 year old children who had previously received 2 catch up doses (at 12,14 or 18,20 or 24,26 months) of the same vaccine according to different schedules, are reported.	Day 31 (1 month post vaccination)	No
Secondary	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.	The GMRs of GMTs following a third dose of rMenB+OMV NZ vaccine (one month post 3rd dose/persistence at 48 months) in children, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of the same vaccine according to different schedules, are reported.	Day 31 (1 month post vaccination)	No
Secondary	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	The percentage of subjects with a four-fold increase in hSBA titers following a third dose of rMenB+OMV NZ vaccine, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules,are reported.; Fourfold increase is defined as- for subjects with a pre-vaccination titer <1:2 to a post-vaccination titer =1:8 and for subjects with a pre-vaccination titer =1:2 to a post-vaccination titer = 4 fold pre-vaccination titer.	Day 31 (1 month post vaccination)	No
Secondary	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.	The sufficiency of immune response is reported in terms of percentages of subjects with hSBA =1:5 and =1:8 in response of two catch up doses of rMenB+OMV NZ vaccine, administered two months apart, in children at 4 years of age.; Immune response was considered sufficient if the lower limit of the two-sided 95% CI for the percentage of subjects achieving hSBA = 1:5 at one month after the two-dose series was = 70% for all three indicator (H44/76; 5/99 and NZ 98/254) strains.; Immune sufficiency was not applicable for M10713 strain.	Day 91 (1 month post second vaccination)	No
Secondary	GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	The GMTs in children who received two catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months of age are reported.	Day 91 (1 month post second vaccination)	No
Secondary	GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	The GMR of GMTs(one month post dose 2/baseline) in children following a two catch up dose of rMenB+OMV NZ at 48 and 50 months of age are reported.	Day 91 (1 month post second vaccination)	No
Secondary	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	The percentages of subjects with 4-fold increase in hSBA titers, one month following a two catch up dose of rMenB+OMV NZ at 4 years of age are reported.	Day 91 (1 month post second vaccination)	No
Secondary	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)	The safety and tolerability of the 5th dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules in the earlier studies is reported as number of subjects with solicited local and systemic adverse events.	From day 1 to day 7 after vaccination	No
Secondary	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)	The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with solicited local and systemic adverse events.	From day 1 to day 7 after vaccination	No
Secondary	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	The safety and tolerability of rMenB+OMV NZ vaccine in 4 year old children who received 2 catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months, is reported as number of subjects with solicited local* and systemic adverse events.	From day 1 to day 7 after any vaccination	No
Secondary	Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	The safety and tolerability of the 5th dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules in the earlier studies is reported as number of subjects with unsolicited AEs, Serious Adverse Events (SAE), AEs leading to premature withdrawal.	From day 1 to study termination	No
Secondary	Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with Unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to premature withdrawal.	From day 1 to study termination	No
Secondary	Number of Subjects Reporting Unsolicited AEs After Any Vaccination.	The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to premature withdrawal.	From day 1 to study termination	No