Clinical trial NCT01339923: A Phase 3B, Open Label, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered Alone to Healthy Infants According to Different Immunization Schedules and to Healthy Children Aged 2 to 10 Years
Official title: A Phase 3B, Open Label, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered Alone to Healthy Infants According to Different Immunization Schedules and to Healthy Children Aged 2 to 10 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningococcal Disease
Meningococcal Meningitis
Keywords: Meningococcal disease
Vaccines
intercalated administration
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-04-21
Enrollment: 1409
Sex: ALL
Minimum age (years): 71
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The proposed study is aimed at assessing the safety and immunogenicity of rMenB+OMV NZ when administered alone without routine infant vaccines to healthy infants in their first year of life according to different two and three dose immunization schedules, which are suitable to be adopted by various national programs. This study will also investigate antibody persistence post primary series and administration of a subsequent booster dose of rMenB+OMV NZ at 11 months of age. In addition, this study will assess the safety and immunogenicity of two catch-up doses of rMenB+OMV NZ when administered to healthy children 2 to 10 years of age.

This study will also evaluate the safety and immunogenicity of the concomitant administration of rMenB+OMV NZ with meningococcal C conjugate vaccine (MenC-CRM) according to a 3, 5 and 12-month schedule.


Eligibility criteria: Inclusion Criteria:

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

   * Healthy infants 2½ months of age (71 -79 days, inclusive), (only applicable to group I)
   * Healthy infants 3½ months of age (101 -109 days, inclusive), (only applicable to group II)
   * Healthy infants 6 months of age (only applicable to group III) (The age window is defined as the first day the subject turns 6 months of age up to the day before the subject turns 7 months of age).
   * Healthy children 2 to 5 years of age (only applicable to group IVa) (The age window is defined as the first day the subject turns 2 years of age up to the day before the subject turns 6 years of age).
   * Healthy children 6 to 10 years of age (only applicable to group IVb) (The age window is defined as the first day the subject turns 6 years of age up to the day before the subject turns 11 years of age).
   * Healthy infants 3 months of age (83-104 days, inclusive), (only applicable to Group V and VI).
2. 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;
3. Available for all the visits scheduled in the study;
4. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

Exclusion Criteria:

1. Individuals whose parent(s)/legal guardian(s) are unwilling or unable to give written informed consent to participate in the study;
2. Children's parents or legal guardian who are not able to comprehend and to follow all required study procedures for the whole period of the study.
3. History of any meningococcal B vaccine administration;
4. Previous ascertained or suspected disease caused by N. meningitidis;
5. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;
6. History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component
7. Significant acute or chronic infection within the previous 7 days or temperature 38° C within the previous day of receiving the study vaccine;
8. Antibiotics treatment within 6 days prior to enrollment;
9. Individuals with history of allergy to vaccine components.
10. 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, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition);
11. Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, use of high dose systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within 14 days prior to enrollment (use of low or moderate doses of inhaled steroids is not an exclusion);
12. Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 90 days prior to enrollment.
13. Receipt of, or intent to immunize with, any other vaccine(s) within 7 days prior to enrollment.
14. Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
15. Family members and household members of research staff
16. Individuals with history or any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
17. History of any meningococcal C vaccine administration (Only applicable to group V and VI).
18. History of any Pneumococcal vaccine administration (Only applicable to group V and VI).

Primary outcomes:
measure: Percentages of Subjects With Serum Bactericidal Activity Using Human Serum (hSBA) Titers ≥ 4 or hSBA Titers ≥ 5 (Strain M10713) Following a 2-dose Primary Series of rMenB+OMV Vaccination.
timeFrame: 1 month after second vaccination
Secondary outcomes:
measure: Percentages of Subjects With hSBA Titers ≥ 4, hSBA Titers ≥ 5 (Strain M10713) and hSBA ≥ 8 Following a 3-dose Primary Series of rMenB+OMV Vaccination
timeFrame: 1 month after third vaccination
measure: Percentages of Subjects With hSBA Titers ≥ 4 or hSBA Titers ≥ 5 (Strain M10713) and hSBA ≥ 8 Following a 2-dose Catch-up Series of rMenB+OMV Vaccination
timeFrame: 1 month after second vaccination
measure: Percentages of Subjects Achieving Four-fold Rise Over Baseline hSBA Titers Following a 2-dose Catch-up Series of rMenB+OMV Vaccination
timeFrame: 1 month after second vaccination
measure: Geometric Mean hSBA Titers (GMTs) Following 2 or 3 Dose Primary Series of Vaccination With rMenB+OMV
timeFrame: 1 month after primary series vaccination
measure: Geometric Mean hSBA Titers (GMTs) After First Infant Vaccination With rMenB+OMV.
timeFrame: 1, 1.5 or 2 months after first infant vaccination
measure: Percentages of Subjects With hSBA Titers ≥ 4 or hSBA Titers ≥ 5 and hSBA ≥ 8 After First Infant Vaccination With rMenB+OMV
timeFrame: Post- first dose (1 month for B_2h3h5_11b, 1.5 month for B_3h5_11b and 2 months for B_68_11b after 1st vaccination)
measure: Percentages of Subjects With hSBA Titers ≥ 4 or hSBA Titers ≥ 5 and hSBA ≥ 8 Following a Booster Dose of rMenB+OMV Vaccination
timeFrame: 1 month post-booster dose
measure: Antibody Persistence in Terms of Percentages of Subjects With hSBA Titers ≥ 4 or hSBA Titers ≥ 5 (M10713) and hSBA ≥ 8 Following 2 or 3-dose Primary Series of Vaccination With rMenB+OMV NZ
timeFrame: 11 months of age (persistence)
measure: Antibody Persistence in Terms of Geometric Mean Titers Following 2 or 3-dose Primary Series of Vaccination With rMenB+OMV NZ
timeFrame: 11 months of age (persistence)
measure: Geometric Mean ELISA Concentrations Against Vaccine Antigen 287-953 Following 2 or 3-dose Primary Series and Booster Dose of Vaccination With rMenB+OMV NZ
timeFrame: 1 month after primary vaccination, pre-booster vaccination (persistence) and 1 month after booster vaccination
measure: Geometric Mean ELISA Concentrations Against Vaccine Antigen 287-953 After a Two Dose Catch-up rMenB+OMV NZ Immunization Series in Children 2-10 Years of Age
timeFrame: 1 month after second vaccination
measure: Percentages of Subjects With hSBA Titers ≥ 8 Against Serogroup C Following Concomitant Administration of rMenB+OMV NZ With MenC-CRM or MenC-CRM Alone
timeFrame: Baseline, 1 month after second vaccination and 1 month after booster vaccination
measure: GMTs Following Concomitant Administration of rMenB+OMV NZ With MenC-CRM or MenC-CRM Alone
timeFrame: 1 month after second vaccination, 1 month after booster vaccination
measure: GMTs Following Concomitant Administration of rMenB+OMV NZ With MenC-CRM or MenC-CRM Alone - Persistence
timeFrame: Pre-booster vaccination (persistence; 12 months of age)
measure: Percentages of Subjects With hSBA Titers ≥ 4 or hSBA Titers ≥ 5 (M10713) and hSBA ≥ 8 Following Concomitant Administration of rMenB+OMV NZ With MenC-CRM
timeFrame: 1 month after second vaccination and 1 month after booster vaccination
measure: GMTs Against N. Meningitidis Serogroup B Strains Following Concomitant Administration of rMenB+OMV NZ With MenC-CRM
timeFrame: 1 month after second vaccination, pre-booster vaccination and 1 month after booster vaccination
measure: Geometric Mean ELISA Concentrations Against Vaccine Antigen 287-953 Following Concomitant Administration of rMenB+OMV NZ With MenC-CRM
timeFrame: 1 month after second vaccination, pre-booster vaccination and 1 month after booster vaccination
measure: Geometric Mean ELISA Concentrations Against Vaccine Antigen 287-953 Following Concomitant Administration of rMenB+OMV NZ With MenC-CRM - Persistence
timeFrame: Pre-booster vaccination (persistence; 12 months of age)
measure: Number of Subjects Who Reported Immediate Reactions Within 30 Minutes After Any Vaccination With rMenB+OMV NZ
timeFrame: Within 30 minutes after any vaccination
measure: Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) Following a 3 or 4-dose Regimen of rMenB+OMV NZ
timeFrame: Day 1 to day 7 after any vaccination
measure: Number of Subjects Who Reported Immediate Reactions Within 30 Minutes After Any Vaccination - Groups B_02_2_5 and B_02_6_10
timeFrame: Within 30 minutes after any vaccination
measure: Number of Subjects With Solicited Local and Systemic AEs in Groups B_02_2_5 and B_02_6_10
timeFrame: Day 1 to day 7 after any vaccination
measure: Number of Subjects Who Reported Immediate Reactions Within 30 Minutes After Any rMenB+OMV NZ or MenC-CRM Vaccination
timeFrame: Within 30 minutes after any vaccination
measure: Number of Subjects With Solicited Local and Systemic AEs in Groups BC_35_12 and C_35_12 After Any rMenB+OMV NZ or MenC-CRM Vaccination
timeFrame: Day 1 to day 7 after any vaccination
measure: Number of Subjects Reporting Unsolicited AEs Following Any Vaccination With rMenB+OMV NZ in Groups B_2h3h5_11, B_3h5_11 and B_68_11
timeFrame: Until 12 months of age; Day 1 to day 7 (All AEs)
measure: Number of Subjects Reporting Unsolicited AEs Following Any Vaccination With rMenB+OMV NZ in Groups B_02_2_5 and B_02_6_10
timeFrame: Day 1 to day 7 (All AEs). Throughout the study period (SAEs, medically attended or leading to premature withdrawal AEs)
measure: Number of Subjects Reporting Unsolicited AEs Following Any Vaccination With rMenB+OMV NZ in Group BC_35_12 and C_35_12
timeFrame: Day 1 to Day 301 for BC_35_12 and C_35_12, Day 302 to Day 391 for C_35_12; Day 1 to day 7 (All AEs)
Other outcomes:
Locations:
city: Rua dos Coelhos, 300 - Boa Vista
country: Brazil
facility: Site 55 - Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
state: Recife/PE
city: Largo de Roma
country: Brazil
facility: Site 54- Associação Obras Sociais Irmã Dulce, Avenida Bonfim, nº 161
state: Salvador/BA-CEP
city: Rua Borges Lagoa 770
country: Brazil
facility: Site 53 - CRIE UNIFESP
state: Sao Paulo
city: Rua Marselhesa 500 Vila Clementino
country: Brazil
facility: Site 50 - Associacao Fundo de Incentivo a Psicofarmacologia
state: Sao Paulo
city: Honved utca 2
country: Hungary
facility: Site 37 - Praxis Dr Julianna Kovacs
state: Bordany
city: Poth Iren u 80
country: Hungary
facility: Site 40 - General Pediatric Practice Hacsek
state: Budapest
city: Szentharomsag ter 10
country: Hungary
facility: Site 42 - Praxis Dr Eszter Bari
state: Csongrad
city: Bajcsi ut 32
country: Hungary
facility: Site 34 - General Pediatric Practice Somorjai
state: Debrecen
city: Fo utca 12
country: Hungary
facility: Site 32 - Praxis Dr Eleonora Konya
state: Malyi
city: Kando Kalman utca 1
country: Hungary
facility: Site 31 - General Practice Dr Olga Fekete
state: Miskolc
city: Selyemret u. 1.
country: Hungary
facility: Site 30 - General Practice Dr Simko
state: Miskolc
city: Szent Istvan u 10
country: Hungary
facility: Site 33 - General Pediatric Practice Ujhelyi
state: Nyiregyhaza
city: Csongradi sgt 63
country: Hungary
facility: Site 35 - Praxis Dr Eva Kovacs
state: Szeged
city: Debreceni utca 10-14
country: Hungary
facility: Site 36 - General Practice Dr Edit Oszlacs
state: Szeged
city: Av Alfonso Ugarte
country: Peru
facility: Site 80 - Hospital Nacional docente Madre Nino San Bartolome
state: Lima
city: Jr Jose de la Torre Ugarte Lince
country: Peru
facility: Site 82 - Investigaciones Medicas en Salud INMENSA
state: Lima
city: Jr Paraguay Cercado de Lima
country: Peru
facility: Site 81 - Via Libre
state: Lima
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: Ourense
country: Spain
facility: Site 11
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
role: STUDY_CHAIR
References:
citation: Safadi MAP, Martinon-Torres F, Weckx LY, Moreira ED Junior, da Fonseca Lima EJ, Willemsen A, Toneatto D, Habib MA, Borys D. Immunogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered concomitantly with the meningococcal serogroup B (4CMenB) vaccine in infants: A post-hoc analysis in a phase 3b, randomised, controlled trial. Vaccine. 2019 Aug 14;37(35):4858-4863. doi: 10.1016/j.vaccine.2019.07.021. Epub 2019 Jul 18.
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.
citation: P Safadi MA, Martinon-Torres F, Weckx LY, Moreira ED Junior, da Fonseca Lima EJ, Mensi I, Calabresi M, Toneatto D. Immunogenicity and safety of concomitant administration of meningococcal serogroup B (4CMenB) and serogroup C (MenC-CRM) vaccines in infants: A phase 3b, randomized controlled trial. Vaccine. 2017 Apr 11;35(16):2052-2059. doi: 10.1016/j.vaccine.2017.03.002. Epub 2017 Mar 18.