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

NCT01894919 | Completed Phase 3 Results

• 2 other identifiers: V72_28E12012-000657-30
• Study Type: interventional
• Target: 851
• Locations: 2 countries
• Sites: 17

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.

Conditions

Meningoccocal Disease; Meningococcal Meningitis

Keywords

Meningococcal B disease,; Antibody persistence

Outcome Measures

Primary Outcomes (5)

• Percentage of Subjects With Human Serum Bactericidal Activity Titers (hSBA) ≥ 4 or ≥ 5 Against Neisseria Meningitidis (N. Meningitidis) Serogroup B Strains

  The antibody persistence in subjects, 24 to 36 months after completion of Bexsero® vaccination course in the parent study according to different schedules, is presented in terms of the percentage of subjects in each vaccine group, with hSBA titers ≥ 4 for what concerns the H44/76, 5/99 and NZ98/254 strains, and hSBA titers ≥ 5 for M10713 strain, alongside with the corresponding antibody responses in age-matched vaccine naïve subjects at baseline. The functional bactericidal antibodies directed against serogroup B meningococcal were assessed by the Serum Bactericidal Assay (SBA) using human serum as the source of exogenous complement (hSBA).

  24-36 months after booster dose in the parent study; baseline for vaccine-naïve subjects

• Percentage of Subjects With hSBA Titers ≥ 8 Against N.Meningitidis Serogroup B Strains

  The antibody persistence in subjects, 24 to 36 months after completion of Bexsero® vaccination course in the parent study according to different schedules is presented in terms of the percentage of subjects in each vaccine group with hSBA titers ≥ 8, alongside with the corresponding antibody responses in age matched vaccine naïve subjects at baseline.

  At 24-36 months after booster dose in the parent study: baseline for vaccine-naïve subjects

• The hSBA Geometric Mean Titers (GMTs) Against N.Meningitidis Serogroup B Strains

  The hSBA antibody titers in subjects, 24 to 36 months after completion of Bexsero® vaccination course according to different schedules in the parent study, are presented in terms of vaccine-group-specific GMTs, alongside with the corresponding antibody responses in age-matched vaccine-naïve subjects at baseline.

  24-36 months after booster dose in the parent study; baseline for vaccine-naïve subjects

• 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.

  The within-subjects GMR of GMTs at 24 to 36 months versus 1 month after completion of Bexsero® vaccination course according to different schedules vaccination in parent study are reported.

  At Day 1 in this study over one month after the completion of the vaccination course in the parent study

• The Geometric Mean Ratio (GMR) of hSBA GMTs Against N. Meningitidis Serogroup B, 24 to 36 Months Versus Visit 1 in the Parent Study.

  The within-subjects GMR of GMTs at 24 to 36 months versus visit 1 in the vaccination course according to different schedules vaccination in the parent study are reported.

  At Day 1 in this study over visit 1 in the vaccination course in the parent study

Secondary Outcomes (19)

• Percentage of Subjects With hSBA Titers ≥4 or ≥ 5 Against N.Meningitidis Serogroup B, After Receiving Bexsero® Booster Vaccination in This Study.

  At 24-36 months (Visit 1) and one month after booster vaccination (Day 31)

• Percentage of Subjects With hSBA Titers ≥ 8 Against N.Meningitidis serogroupB, After Receiving Bexsero® Booster Vaccination in This Study.

  At 24-36 months (Visit 1) and one month after booster vaccination (Day 31)

• Percentage of Subjects With Four-fold Rise in hSBA Titers, After Receiving Bexsero® Vaccination in This Study.

  One month after booster vaccination (day 31)/24-36 months (Visit 1)

• Percentage of Subjects With Four-fold Rise in hSBA Titers, One Month After Receiving Bexsero® Vaccination in This Study

  From post primary visit in the parent study to visit 2 in this extension study

• Percentage of Subjects With Four-fold Rise in hSBA Titers, One Month After Receiving Bexsero® Vaccination in This Study.

  From pre primary visit in the parent study (Visit 1) to visit 2 in this extension study

Study Arms (13)

2H3H511_V

EXPERIMENTAL

In the parent study V72\_28 (NCT01339923), subjects received three primary doses and one booster dose of Bexsero® vaccine at 2.5, 3.5 and 5 months and at 11 months of age, respectively. The subjects in this group received a 5th dose of Bexsero® vaccine in the present study.

Biological: Bexsero® vaccine (1 dose at study month zero)

2H3H511_NV

NO INTERVENTION

In the parent study V72\_28 (NCT01339923), subjects received three primary doses and one booster dose of Bexsero® vaccine at 2.5, 3.5 and 5 months and at 11 months of age, respectively. These subjects were evaluated only for persistence.

3H5_11_V

EXPERIMENTAL

In the parent study V72\_28 (NCT01339923), subjects received two primary doses and one booster dose of Bexsero® vaccine at 3.5 and 5 months and at 11 months of age, respectively. These subjects received a 4th dose of Bexsero® vaccine in the present study.

Biological: Bexsero® vaccine (1 dose at study month zero)

3H5_11_NV

NO INTERVENTION

In the parent study V72\_28 (NCT01339923), subjects received two primary doses and one booster dose of Bexsero® vaccine at 3.5 and 5 months and at 11 months of age, respectively. These subjects were evaluated only for persistence.

68_11_V

EXPERIMENTAL

In the parent study V72\_28 (NCT01339923), subjects received two primary doses and one booster dose of Bexsero® vaccine at 6 and 8 months and at 11 months of age, respectively. These subjects received a 4th dose of Bexsero® vaccine in the present study.

Biological: Bexsero® vaccine (1 dose at study month zero)

68_11_NV

NO INTERVENTION

In the parent study V72\_28 (NCT01339923), subjects received two primary doses and one booster dose of Bexsero® vaccine at 6 and 8 months and at 11 months of age, respectively. These subjects were evaluated only for persistence.

02_2_5_V

EXPERIMENTAL

In the parent study V72\_28 (NCT01339923), these subjects received two catch-up doses of Bexsero® vaccine, two months apart. These subjects received a 3rd dose of Bexsero® vaccine in the present study.

Biological: Bexsero® vaccine (1 dose at study month zero)

02_2_5_NV

NO INTERVENTION

In the parent study V72\_28 (NCT01339923), these subjects received two catch-up doses of Bexsero® vaccine, two months apart. These subjects were evaluated only for persistence.

02_6_10_V

EXPERIMENTAL

In the parent study V72\_28 (NCT01339923), these subjects received two catch-up doses of Bexsero® vaccine, two months apart. These subjects received a 3rd dose of Bexsero® vaccine in the present study.

Biological: Bexsero® vaccine (1 dose at study month zero)

02_6_10_NV

NO INTERVENTION

In the parent study V72\_28 (NCT01339923), these subjects received two catch-up doses of Bexsero® vaccine, two months apart. These subjects were evaluated only for persistence.

NAIVE 123

EXPERIMENTAL

Newly recruited naïve subjects who received two catch-up doses of Bexsero® vaccine, one month apart, in the present study.

Biological: Bexsero® vaccine (2 doses 1 month apart)

NAIVE_4A

EXPERIMENTAL

Newly recruited naïve subjects who received two catch-up doses of Bexsero® vaccine, one month apart, in the present study.

Biological: Bexsero® vaccine (2 doses 1 month apart)

NAIVE_4B

EXPERIMENTAL

Newly recruited naïve subjects who received two catch-up doses of Bexsero® vaccine, one month apart, in the present study.

Biological: Bexsero® vaccine (2 doses 1 month apart)

Interventions

Bexsero® vaccine (1 dose at study month zero) BIOLOGICAL

02_2_5_V; 02_6_10_V; 2H3H511_V; 3H5_11_V; 68_11_V

Bexsero® vaccine (2 doses 1 month apart) BIOLOGICAL

NAIVE 123; NAIVE_4A; NAIVE_4B

Eligibility Criteria

• Age: 35 Months - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• For naïve subjects newly enrolled:
• Healthy infants and children according to the following age groups:
• 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),
• 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).
• 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).
• for whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;
• for whom a parent/legal guardian confirmed availability for the visit scheduled in the study;
• 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):
• for whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;
• for whom a parent/legal guardian confirmed availability for the visit scheduled in the study;
• in good health as determined by medical history, physical examination, clinical judgment of the investigator
• 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

You may not qualify if:

• For naïve subjects newly enrolled:
• History of any serogroup B meningococcal vaccine administration;
• Previous known or suspected disease caused by N. meningitidis;
• Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection or colonization;
• History of severe allergic reaction after previous vaccinations or hypersensitivity to any component of the vaccine;
• Pregnancy or nursing (breastfeeding) mothers;
• 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;
• 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
• History of seizure, any progressive neurological disease or Guillain Barré Syndrome (exception: one self-limited febrile seizure is acceptable).
• Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
• 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.
• Intent to participate in another clinical study during this study.

Sponsors & Collaborators

• Novartis Vaccines: lead
• GlaxoSmithKline: collaborator

Study Sites (17)

Site 34, General Pediatric Practice Somorjai

Debrecen, Bajcsi Ut 32, 4025, Hungary

Location

Site 35, Praxis Dr Eva Kovacs

Szeged, Csongradi Sgt 63, 6723, Hungary

Location

Site 36, General Practice Dr Edit Oszlacs

Szeged, Debreceni Utca 10-14, 6723, Hungary

Location

Site 37, Praxis Dr Julianna Kovacs

Bordány, Honved Utca 2, 6795, Hungary

Location

Site 31, General Practice Dr Olga Fekete

Miskolc, Kando Kalman Utca 1, 3534, Hungary

Location

Site 40, General Pediatric Practice Hacsek

Budapest, Poth Iren U 80, 1188, Hungary

Location

Site 30, General Practice Dr Simko

Miskolc, Selyemret U. 1., 3527, Hungary

Location

Site 33, General Pediatric Practice Ujhelyi

Nyíregyháza, Szent Istvan U 10, 4400, Hungary

Location

Site 42, Praxis Dr Eszter Bari

Csongrád, Szentharomsag Ter 10, 6640, Hungary

Location

Site 15

Almería, 04007, Spain

Location

Site 16

Almería, 04120, Spain

Location

Site 20

Barcelona, 08195, Spain

Location

Site 17

Madrid, 28041, Spain

Location

Site 18

Madrid, 28935, Spain

Location

Site 13

Pontevedra, 36002, Spain

Location

Site 10

Santiago de Compostela, 15706, Spain

Location

Site 14

Seville, 41014, Spain

Location

Related Publications (1)

• 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.

  PMID: 29253560 DERIVED

MeSH Terms

Conditions

Meningitis, Meningococcal

Condition Hierarchy (Ancestors)

Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Results Point of Contact

• Title: Posting Director
• Organization: Novartis Vaccines

RegistryContactVaccinesUS@novartis.com

Study Officials

• Novartis Vaccines and Diagnostics

  Novartis Vaccines

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2013
• First Posted: July 10, 2013
• Study Start: June 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: November 1, 2015
• Last Updated: November 30, 2021
• Results First Posted: December 7, 2018

Record last verified: 2018-05

Locations

ES (8); HU (9)