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

NCT ID: NCT01339923

Last Updated: 2016-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1409 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

B_2h3h5_11

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.

Group Type: EXPERIMENTAL

rMenB + OMV NZ vaccine

Intervention Type: BIOLOGICAL

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

B_3h5_11

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.

Group Type: EXPERIMENTAL

rMenB + OMV NZ vaccine

Intervention Type: BIOLOGICAL

2 doses (3.5, 5 months of age) plus booster (11 months of age)

B_68_11

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.

Group Type: EXPERIMENTAL

rMenB + OMV NZ vaccine

Intervention Type: BIOLOGICAL

2 doses (6, 8 months of age) plus booster (11 months of age)

B_02_2_5

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.

Group Type: EXPERIMENTAL

rMenB + OMV NZ vaccine

Intervention Type: BIOLOGICAL

2 doses 2 months apart

B_02_6_10

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.

Group Type: EXPERIMENTAL

rMenB + OMV NZ vaccine

Intervention Type: BIOLOGICAL

2 doses 2 months apart

BC_35_12

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.

Group Type: EXPERIMENTAL

Meningococcal C oligosaccharide conjugated vaccine

Intervention Type: BIOLOGICAL

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

Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed.

Intervention Type: BIOLOGICAL

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

rMenB + OMV NZ vaccine

Intervention Type: BIOLOGICAL

Schedule 3, 5, 12 rMenB + OMV vaccine

C_35_12

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.

Group Type: EXPERIMENTAL

Meningococcal C oligosaccharide conjugated vaccine

Intervention Type: BIOLOGICAL

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

Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed.

Intervention Type: BIOLOGICAL

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

rMenB + OMV NZ vaccine

Intervention Type: BIOLOGICAL

Schedule 13,15 rMenB + OMV vaccine

Interventions

rMenB + OMV NZ vaccine

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

Intervention Type: BIOLOGICAL

rMenB + OMV NZ vaccine

2 doses (3.5, 5 months of age) plus booster (11 months of age)

Intervention Type: BIOLOGICAL

rMenB + OMV NZ vaccine

2 doses (6, 8 months of age) plus booster (11 months of age)

Intervention Type: BIOLOGICAL

rMenB + OMV NZ vaccine

2 doses 2 months apart

Intervention Type: BIOLOGICAL

Meningococcal C oligosaccharide conjugated vaccine

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

Intervention Type: BIOLOGICAL

Pneumococcal polysaccharide conjugate vaccine, 10 valent adsorbed.

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

Intervention Type: BIOLOGICAL

rMenB + OMV NZ vaccine

Schedule 3, 5, 12 rMenB + OMV vaccine

Intervention Type: BIOLOGICAL

rMenB + OMV NZ vaccine

Schedule 13,15 rMenB + OMV vaccine

Intervention Type: BIOLOGICAL

Other Intervention Names

rMenB for Group I; rMenB for Group II; rMenB for Group III; rMenB for Group IV; rMenB for Group V; rMenB for Group VI

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).

• Minimum Eligible Age: 71 Days
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Vaccines

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Vaccines

Role: STUDY_CHAIR

Novartis Vaccines

Locations

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

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

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

Largo de Roma, Salvador/BA-CEP, Brazil

Site 53 - CRIE UNIFESP

Rua Borges Lagoa 770, São Paulo, Brazil

Site 50 - Associacao Fundo de Incentivo a Psicofarmacologia

Rua Marselhesa 500 Vila Clementino, São Paulo, Brazil

Site 37 - Praxis Dr Julianna Kovacs

Honved Utca 2, Bordany, Hungary

Site 40 - General Pediatric Practice Hacsek

Poth Iren U 80, Budapest, Hungary

Site 42 - Praxis Dr Eszter Bari

Szentharomsag Ter 10, Csongrád megye, Hungary

Site 34 - General Pediatric Practice Somorjai

Bajcsi Ut 32, Debrecen, Hungary

Site 32 - Praxis Dr Eleonora Konya

Fo Utca 12, Malyi, Hungary

Site 31 - General Practice Dr Olga Fekete

Kando Kalman Utca 1, Miskolc, Hungary

Site 30 - General Practice Dr Simko

Selyemret U. 1., Miskolc, Hungary

Site 33 - General Pediatric Practice Ujhelyi

Szent Istvan U 10, Nyiregyhaza, Hungary

Site 35 - Praxis Dr Eva Kovacs

Csongradi Sgt 63, Szeged, Hungary

Site 36 - General Practice Dr Edit Oszlacs

Debreceni Utca 10-14, Szeged, Hungary

Site 80 - Hospital Nacional docente Madre Nino San Bartolome

Av Alfonso Ugarte, Lima, Peru

Site 82 - Investigaciones Medicas en Salud INMENSA

Jr Jose de La Torre Ugarte Lince, Lima, Peru

Site 81 - Via Libre

Jr Paraguay Cercado de Lima, Lima, Peru

Site 15

Almería, , Spain

Site 16

Almería, , Spain

Site 20

Barcelona, , Spain

Site 17

Madrid, , Spain

Site 18

Madrid, , Spain

Site 11

Ourense, , Spain

Site 13

Pontevedra, , Spain

Site 10

Santiago de Compostela, , Spain

Site 14

Seville, , Spain

Countries

Brazil; Hungary; Peru; Spain

References

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.

Reference Type: DERIVED

PMID: 31327652 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29253560 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28318767 (View on PubMed)

Other Identifiers

V72_28

Identifier Type: -

Identifier Source: org_study_id