Clinical trial NCT01894919: Antibody Persistence, and Safety and Tolerability of a Booster Dose of the Meningococcal B Vaccine After the Completion of the Vaccination Course in Study V72_28
Official title: A Phase IIIb, Open Label, Multi Center Extension Study of V72_28 to Assess Antibody Persistence, and the Safety and Tolerability of a Booster Dose After the Completion of the Vaccination Course in Study V72_28
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningoccocal Disease
Meningococcal Meningitis
Keywords: Meningococcal B disease,
Antibody persistence
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2013-07-10
Enrollment: 851
Sex: ALL
Minimum age (years): 35
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this extension study is to explore the antibody persistence 24 to 36 months after the last dose of vaccine, in infants that received a two or three dose primary series plus a booster dose at 11 months of age, of the Novartis meningococcal B vaccine (Bexsero®) in groups I to III of the parent V72_28 study.

This study will also explore the antibody persistence 24 to 36 months after two catch-up doses of the Novartis meningococcal B vaccine (Bexsero®) administered in children (2 to 10 years old) in group IV of the parent V72_28 study.


Eligibility criteria: Inclusion Criteria:

For naïve subjects newly enrolled:

1. Healthy infants and children according to the following age groups:

   1. Healthy subjects from 35 to 47 months of age, (only applicable to group K) (The age window is defined as the first day the subject turns 35 months of age up to the day before the subject turns 48 months of age),
   2. Healthy subjects 4 to 7 years of age (only applicable to group L) (The age window is defined as the first day the subject turns 4 years of age up to the day before the subject turns 8 years of age).
   3. Healthy subjects 8 to 12 years of age (only applicable to group M) (The age window is defined as the first day the subject turns 8 years of age up to the day before the subject turns 13 years of age).
2. for whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;
3. for whom a parent/legal guardian confirmed availability for the visit scheduled in the study;
4. in good health as determined by medical history, physical examination, clinical judgment of the investigator.

For Subjects who participated in the V72_28 study (Follow-on Subjects):

1. for whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;
2. for whom a parent/legal guardian confirmed availability for the visit scheduled in the study;
3. in good health as determined by medical history, physical examination, clinical judgment of the investigator
4. who have completed the vaccination course in the V72_28 study and have received their last vaccination 24 to 36 months before enrollment in V72_28E1

Exclusion Criteria:

For naïve subjects newly enrolled:

1. History of any serogroup B meningococcal vaccine administration;
2. Previous known or suspected disease caused by N. meningitidis;
3. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection or colonization;
4. History of severe allergic reaction after previous vaccinations or hypersensitivity to any component of the vaccine;
5. Pregnancy or nursing (breastfeeding) mothers;
6. Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study. Oral, injected or implanted hormonal contraceptive, barrier methods (condom or diaphragm with spermicide), intrauterine device, surgical sterilization, transdermal delivery, congenital sterility or sexual abstinence are considered acceptable forms of birth control. If sexually active the subject must have been using one of the accepted birth control methods at least two months prior to study entry;
7. Known or suspected autoimmune disease or impairment/alteration of the immune system resulting from (for example):

   * Receipt of any chronic immunosuppressive therapy
   * Receipt of any chronic immunostimulants
   * Immune deficiency disorder, or known HIV infection
8. History of seizure, any progressive neurological disease or Guillain Barré Syndrome (exception: one self-limited febrile seizure is acceptable).
9. Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
10. Subject's parent(s) or legal guardian(s) are not able to comprehend and to follow all required study procedures for the whole period of the study.
11. Intent to participate in another clinical study during this study.
12. Family members and household members of study staff;
13. History or any illness/condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives or pose additional risk to the subjects due to participation in the study.
14. Any significant chronic infection.
15. Any serious chronic or progressive disease according to judgment of the investigator (e.g. neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).

For Subjects who participated in the V72_28 study (Follow-on Subjects):

Exclusion criteria are the same as for naïve subjects, with the exception of criterion 1.

Primary outcomes:
measure: Percentage of Subjects With Human Serum Bactericidal Activity Titers (hSBA) ≥ 4 or ≥ 5 Against Neisseria Meningitidis (N. Meningitidis) Serogroup B Strains
timeFrame: 24-36 months after booster dose in the parent study; baseline for vaccine-naïve subjects
measure: Percentage of Subjects With hSBA Titers ≥ 8 Against N.Meningitidis Serogroup B Strains
timeFrame: At 24-36 months after booster dose in the parent study: baseline for vaccine-naïve subjects
measure: The hSBA Geometric Mean Titers (GMTs) Against N.Meningitidis Serogroup B Strains
timeFrame: 24-36 months after booster dose in the parent study; baseline for vaccine-naïve subjects
measure: The Geometric Mean Ratio (GMR) of hSBA GMTs Against N. Meningitidis Serogroup B, 24 to 36 Months Versus 1 Month After Completion of Bexsero® Vaccination Course According to Different Schedules in the Parent Study.
timeFrame: At Day 1 in this study over one month after the completion of the vaccination course in the parent study
measure: The Geometric Mean Ratio (GMR) of hSBA GMTs Against N. Meningitidis Serogroup B, 24 to 36 Months Versus Visit 1 in the Parent Study.
timeFrame: At Day 1 in this study over visit 1 in the vaccination course in the parent study
Secondary outcomes:
measure: Percentage of Subjects With hSBA Titers ≥4 or ≥ 5 Against N.Meningitidis Serogroup B, After Receiving Bexsero® Booster Vaccination in This Study.
timeFrame: At 24-36 months (Visit 1) and one month after booster vaccination (Day 31)
measure: Percentage of Subjects With hSBA Titers ≥ 8 Against N.Meningitidis serogroupB, After Receiving Bexsero® Booster Vaccination in This Study.
timeFrame: At 24-36 months (Visit 1) and one month after booster vaccination (Day 31)
measure: Percentage of Subjects With Four-fold Rise in hSBA Titers, After Receiving Bexsero® Vaccination in This Study.
timeFrame: One month after booster vaccination (day 31)/24-36 months (Visit 1)
measure: Percentage of Subjects With Four-fold Rise in hSBA Titers, One Month After Receiving Bexsero® Vaccination in This Study
timeFrame: From post primary visit in the parent study to visit 2 in this extension study
measure: Percentage of Subjects With Four-fold Rise in hSBA Titers, One Month After Receiving Bexsero® Vaccination in This Study.
timeFrame: From pre primary visit in the parent study (Visit 1) to visit 2 in this extension study
measure: The GMTs Against N.Meningitidis Serogroup B, One Month After Receiving Bexsero® Booster Vaccination in the Present Study.
timeFrame: At Visit 1 and one month post booster vaccination (Day 31)
measure: The Geometric Mean Ratio (GMR) of hSBA Titers, One Month After Receiving Bexsero® Booster Vaccination in the Present Study.
timeFrame: At Day 31 versus Day 1
measure: The Geometric Mean Ratio (GMR) of hSBA Titers, One Month After Receiving Bexsero® Booster Vaccination in the Present Study.
timeFrame: Visit 2 (day 31 in extension study) versus post primary vaccination visit in parent study
measure: Percentage of Subjects With hSBA Titers ≥ 4 or ≥ 5, After Receiving Two Catch up Doses of Bexsero® Vaccination
timeFrame: At Baseline and One month post second vaccination (Day 61)
measure: Percentage of Subjects With hSBA Titers ≥ 8 , After Receiving Two Catch up Doses of Bexsero® Vaccination.
timeFrame: At Baseline and One month post second vaccination (Day 61)
measure: Percentage of Subjects With Four-fold Rise in hSBA Titers, After Receiving Two Catch up Doses of Bexsero® Vaccination.
timeFrame: One month post second vaccination (Day 61)
measure: The GMTs in Subjects Who Received Two Catch up Doses of Bexsero® Vaccination.
timeFrame: At Baseline and One month post second vaccination (Day 61)
measure: The GMRs of hSBA Titers After Two Catch up Doses of Bexsero® Vaccination Versus hSBA Titers at Baseline.
timeFrame: At one month after receiving second vaccination (Day 61) versus baseline (Day 1)
measure: Number of Subjects (35 Months to 7 Years of Age) Reporting Solicited Local and Systemic Adverse Events After Receiving Bexsero® Booster Vaccine.
timeFrame: From day 1 (6 hr) through day 7 after vaccination
measure: Number of Newly Recruited Subjects (Aged 35 Months to 7 Years) Reporting Solicited Local and Systemic Adverse Events After Receiving Catch-up Doses of Bexsero® Vaccine.
timeFrame: From day 1 (6 hr) through day 7 after vaccination
measure: Number of Subjects (8 to 12 Years of Age) Reporting Solicited Local and Systemic Adverse Events After Receiving Bexsero® Booster Vaccine.
timeFrame: From day 1 (6 hr) through day 7 after vaccination
measure: Number of Newly Recruited naïve Subjects (Aged 8 to 12 Years of Age) Solicited Local and Systemic Adverse Events After Receiving Bexsero® Vaccine.
timeFrame: From day 1(6 hr) through day 7 after vaccination
measure: Number of Subjects Reporting Unsolicited Adverse Events After Receiving Bexsero® Vaccination.
timeFrame: From day 1 through day 7 after any vaccination
measure: Number of Subjects Reporting Unsolicited Serious Adverse Events (SAEs), Medically Attended AEs and AEs Leading to Withdrawal for Entire Study Period.
timeFrame: Throughout the entire study period (up to 2 months)
Other outcomes:
Locations:
city: Debrecen
country: Hungary
facility: Site 34, General Pediatric Practice Somorjai
state: Bajcsi Ut 32
city: Szeged
country: Hungary
facility: Site 35, Praxis Dr Eva Kovacs
state: Csongradi Sgt 63
city: Szeged
country: Hungary
facility: Site 36, General Practice Dr Edit Oszlacs
state: Debreceni Utca 10-14
city: Bordany
country: Hungary
facility: Site 37, Praxis Dr Julianna Kovacs
state: Honved Utca 2
city: Miskolc
country: Hungary
facility: Site 31, General Practice Dr Olga Fekete
state: Kando Kalman Utca 1
city: Budapest
country: Hungary
facility: Site 40, General Pediatric Practice Hacsek
state: Poth Iren U 80
city: Miskolc
country: Hungary
facility: Site 30, General Practice Dr Simko
state: Selyemret U. 1.
city: Nyiregyhaza
country: Hungary
facility: Site 33, General Pediatric Practice Ujhelyi
state: Szent Istvan U 10
city: Csongrad
country: Hungary
facility: Site 42, Praxis Dr Eszter Bari
state: Szentharomsag Ter 10
city: Almeria
country: Spain
facility: Site 15
city: Almeria
country: Spain
facility: Site 16
city: Barcelona
country: Spain
facility: Site 20
city: Madrid
country: Spain
facility: Site 17
city: Madrid
country: Spain
facility: Site 18
city: Pontevedra
country: Spain
facility: Site 13
city: Santiago de Compostela
country: Spain
facility: Site 10
city: Sevilla
country: Spain
facility: Site 14
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines and Diagnostics
role: STUDY_CHAIR
References:
citation: Martinon-Torres F, Carmona Martinez A, Simko R, Infante Marquez P, Arimany JL, Gimenez-Sanchez F, Couceiro Gianzo JA, Kovacs E, Rojo P, Wang H, Bhusal C, Toneatto D. Antibody persistence and booster responses 24-36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial. J Infect. 2018 Mar;76(3):258-269. doi: 10.1016/j.jinf.2017.12.005. Epub 2017 Dec 15.