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

NCT01339923 | Completed Phase 3 Results

• 1 other identifier: V72_28
• Study Type: interventional
• Target: 1,409
• Locations: 4 countries
• Sites: 26

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.

Conditions

Meningococcal Disease; Meningococcal Meningitis

Keywords

Meningococcal disease; Vaccines; intercalated administration

Outcome Measures

Primary Outcomes (1)

• 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.

  Immunogenicity was assessed in terms of percentages of subjects with hSBA titers ≥ 4 against N meningitidis serogroup B strains H44/76, 5/99, NZ98/254 and hSBA titers ≥ 5 against strain M10713 following 2-dose primary series of vaccination with rMenB+OMV NZ at 3.5 and 5 months of age or at 6 and 8 months of age. Analysis was done on Full analysis set (FAS)-Primary series.

  1 month after second vaccination

Secondary Outcomes (27)

• 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

  1 month after third vaccination

• 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

  1 month after second vaccination

• Percentages of Subjects Achieving Four-fold Rise Over Baseline hSBA Titers Following a 2-dose Catch-up Series of rMenB+OMV Vaccination

  1 month after second vaccination

• Geometric Mean hSBA Titers (GMTs) Following 2 or 3 Dose Primary Series of Vaccination With rMenB+OMV

  1 month after primary series vaccination

• Geometric Mean hSBA Titers (GMTs) After First Infant Vaccination With rMenB+OMV.

  1, 1.5 or 2 months after first infant vaccination

Study Arms (7)

B_2h3h5_11

EXPERIMENTAL

Subjects, approximately 2.5 months of age, received 3 dose primary vaccination of rMenB+OMV NZ at 2.5, 3.5, 5 months of age, followed by a booster dose at 11 months of age.

Biological: rMenB + OMV NZ vaccine

B_3h5_11

EXPERIMENTAL

Subjects, approximately 3.5 months of age, received 2 dose primary vaccination of rMenB+OMV NZ at 3.5 and 5 months of age, followed by a booster dose at 11 months of age.

Biological: rMenB + OMV NZ vaccine

B_68_11

EXPERIMENTAL

Subjects, approximately 6 months of age, received 2 dose primary vaccination of rMenB+OMV NZ at 6 and 8 months of age, followed by a booster dose at 11 months of age.

Biological: rMenB + OMV NZ vaccine

B_02_2_5

EXPERIMENTAL

Subjects, 2-5 years of age received 2 catch-up doses of rMenB+OMV NZ, each at 0 and 2 months. Blood draw at 0 and 3 months since study start.

Biological: rMenB + OMV NZ vaccine

B_02_6_10

EXPERIMENTAL

Subjects, 6-10 years of age received 2 catch-up doses of rMenB+OMV NZ, each at 0 and 2 months. Blood draw at 0 and 3 months since study start.

Biological: rMenB + OMV NZ vaccine

BC_35_12

EXPERIMENTAL

Subjects, 3 months of age received rMenB+OMV NZ + MenC-CRM and Synflorix concomitantly at 3, 5 and 12 months of age and an additional dose of Synflorix alone dose at 7 months of age.

Biological: Meningococcal C oligosaccharide conjugated vaccine; Biological: Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed.; Biological: rMenB + OMV NZ vaccine

C_35_12

EXPERIMENTAL

Subjects, 3 months of age received MenC-CRM and Synflorix concomitantly at 3, 5 and 12 months of age and an additional dose of Synflorix alone at 7 months of age and rMenB+OMV NZ alone at 13 and 15 months of age.

Biological: Meningococcal C oligosaccharide conjugated vaccine; Biological: Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed.; Biological: rMenB + OMV NZ vaccine

Interventions

rMenB + OMV NZ vaccine BIOLOGICAL

3 doses (2.5, 3.5, 5 months if age) plus booster (11 months of age)

Also known as: rMenB for Group I

B_2h3h5_11

Meningococcal C oligosaccharide conjugated vaccine BIOLOGICAL

Schedule 3, 5, 7, 12, Meningococcal C oligosaccharide conjugated vaccine

BC_35_12; C_35_12

Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed. BIOLOGICAL

Schedule 3, 5, 7, 12 Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed.

BC_35_12; C_35_12

Eligibility Criteria

• Age: 71 Days - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• 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;
• Available for all the visits scheduled in the study;
• Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

You may not qualify if:

• Individuals whose parent(s)/legal guardian(s) are unwilling or unable to give written informed consent to participate in the study;
• 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.
• History of any meningococcal B vaccine administration;
• Previous ascertained or suspected disease caused by N. meningitidis;
• Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;
• History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component
• Significant acute or chronic infection within the previous 7 days or temperature 38° C within the previous day of receiving the study vaccine;
• Antibiotics treatment within 6 days prior to enrollment;
• Individuals with history of allergy to vaccine components.
• 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);
• Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 90 days prior to enrollment.
• Receipt of, or intent to immunize with, any other vaccine(s) within 7 days prior to enrollment.
• 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.
• Family members and household members of research staff
• 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.

Sponsors & Collaborators

• Novartis Vaccines: lead

Study Sites (26)

Site 55 - Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)

Rua Dos Coelhos, 300 - Boa Vista, Recife/PE, 50070-550, Brazil

Location

Site 54- Associação Obras Sociais Irmã Dulce, Avenida Bonfim, nº 161

Largo de Roma, Salvador/BA-CEP, 40420-000, Brazil

Location

Site 53 - CRIE UNIFESP

Rua Borges Lagoa 770, São Paulo, 04038002, Brazil

Location

Site 50 - Associacao Fundo de Incentivo a Psicofarmacologia

Rua Marselhesa 500 Vila Clementino, São Paulo, 04020-060, Brazil

Location

Site 37 - Praxis Dr Julianna Kovacs

Honved Utca 2, Bordany, 6795, Hungary

Location

Site 40 - General Pediatric Practice Hacsek

Poth Iren U 80, Budapest, Hungary

Location

Site 42 - Praxis Dr Eszter Bari

Szentharomsag Ter 10, Csongrád megye, 6640, Hungary

Location

Site 34 - General Pediatric Practice Somorjai

Bajcsi Ut 32, Debrecen, 4025, Hungary

Location

Site 32 - Praxis Dr Eleonora Konya

Fo Utca 12, Malyi, 3434, Hungary

Location

Site 31 - General Practice Dr Olga Fekete

Kando Kalman Utca 1, Miskolc, 3534, Hungary

Location

Site 30 - General Practice Dr Simko

Selyemret U. 1., Miskolc, 3527, Hungary

Location

Site 33 - General Pediatric Practice Ujhelyi

Szent Istvan U 10, Nyiregyhaza, 4400, Hungary

Location

Site 35 - Praxis Dr Eva Kovacs

Csongradi Sgt 63, Szeged, 6723, Hungary

Location

Site 36 - General Practice Dr Edit Oszlacs

Debreceni Utca 10-14, Szeged, 6723, Hungary

Location

Site 80 - Hospital Nacional docente Madre Nino San Bartolome

Av Alfonso Ugarte, Lima, Peru

Location

Site 82 - Investigaciones Medicas en Salud INMENSA

Jr Jose de La Torre Ugarte Lince, Lima, Peru

Location

Site 81 - Via Libre

Jr Paraguay Cercado de Lima, Lima, Peru

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 11

Ourense, 32005, Spain

Location

Site 13

Pontevedra, 36002, Spain

Location

Site 10

Santiago de Compostela, 15706, Spain

Location

Site 14

Seville, 41014, Spain

Location

Related Publications (3)

• 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.

  PMID: 31327652 DERIVED

• 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

• 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.

  PMID: 28318767 DERIVED

MeSH Terms

Conditions

Meningococcal Infections; Meningitis, Meningococcal

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Meningitis, Bacterial; Central Nervous System 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 and Diagnostics

RegistryContactVaccinesUS@novartis.com

Study Officials

• Novartis Vaccines

  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: April 13, 2011
• First Posted: April 21, 2011
• Study Start: April 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 9, 2016
• Results First Posted: January 20, 2016

Record last verified: 2016-03

Locations

BR (4); ES (9); HU (10); PE (3)