Safety, Tolerability and Immunogenicity of Meningococcal B Recombinant Vaccine Administered With or Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules

Meningococcal Infections Clinical Trial

Official title:

A Phase 2b, Open Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered With or Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00721396
• Other study ID #: V72P12
• Status: Completed
• Phase: Phase 2
• First received: July 22, 2008
• Last updated: March 17, 2015
• Start date: August 2008
• Est. completion date: July 2010

Study information

• Verified date: March 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Federal Institute for Drugs and Medical DevicesBelgium: Federal Agency for Medicinal Products and Health ProductsSpain: Agencia Española de Medicamentos y Productos SanitariosItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthCzech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

Primary :1.To demonstrate a sufficient immune response of rMenB+OMV NZ, when given concomitantly with routine infant vaccines to healthy infants at 2, 4 and 6 and 2, 3 and 4 months of age, as measured by percentage of subjects with serum bactericidal activity (SBA) titer ≥1:5, at 1 month after the third vaccination Secondary :To demonstrate that immunogenicity of routine infant vaccines, when given concomitantly with rMenB+OMV NZ to healthy infants at 2, 3 and 4 months of age, was non-inferior to that of routine infant vaccines given without rMenB+OMV NZ. 2. To demonstrate that the immunogenicity of rMenB+OMV NZ when given concomitantly with routine infant vaccines was non-inferior to that of rMenB+OMV NZ given without routine infant vaccines at 2, 4 and 6 months of age. 3. To assess prevalence of meningococcal B antibodies over the study period by evaluation of SBA, at baseline and at 1 month after third vaccination, in subjects- received routine infant vaccine without rMenB+OMV NZ.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1885
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Days to 89 Days

Eligibility

Inclusion Criteria:

• Healthy 2-month old infants (55-89 days, inclusive), who were born after full term pregnancy with an estimated gestational age = 37 weeks and a birth weight = 2.5 kg;

• For whom a parent/legal guardian has given written informed consent after the nature of the study has been explained.

Exclusion Criteria:

• History of any meningococcal B or C vaccine administration;

• prior vaccination with routine infant vaccines (Diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenzae type b (Hib), and Pneumococcal antigens);

• Previous ascertained or suspected disease caused by 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 axillary temperature major or equal to38 degrees within the previous day;

• Antibiotics within 6 days prior to enrollment;

• Any serious chronic or progressive disease;

• Known or suspected impairment or alteration of the immune system;

• Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Meningococcal Infections

Intervention

Biological:
• rMenB+OMV NZ

• combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine

• Pneumococcal vaccine

Locations

Country	Name	City	State
Belgium	Novartis Investigational Site Nr. 55	Antwerp
Belgium	Novartis Investigational Site Nr. 57	Brussels	Brussels-Capital Region
Belgium	Study Investigational Site Nr. 60	Brussels	Brussels-Capital Region
Belgium	Novartis Investigational Site Nr. 59	Edegem	Antwerpen
Belgium	Novartis Investigational Site Nr. 56	Hasselt	Limburg
Belgium	Novartis Investigational Site Nr. 58	Namur
Czech Republic	Novartis Investigational Site Nr. 95	Cervený Kostelec	Hradec Králové
Czech Republic	Novartis Investigational Site Nr. 93	Hradec Králové
Czech Republic	Novartis Investigational Site Nr. 96	Jindrichuv Hradec	South Bohemian
Czech Republic	Novartis Investigational Site Nr. 94	Pardubice
Germany	Novartis Investigational Site Nr. 69	Aschaffenburg	Bavaria
Germany	Novartis Investigational Site Nr. 68	Bad Saulgau	Baden-Württemberg
Germany	Novartis Investigational Site Nr. 73	Baunatal	Hesse
Germany	Novartis Investigational Site Nr. 70	Berlin
Germany	Novartis Investigational Site Nr. 85	Bielefeld	North-Rhine Westphalia
Germany	Novartis Investigational Site Nr. 81	Bochum	North Rhine-Westphalia
Germany	Novartis Investigational Site Nr. 75	Bramsche	Lower Saxony
Germany	Novartis Investigational Site Nr. 71	Bremerhaven	Bremen
Germany	Novartis Investigational Site Nr. 65	Bretten	Baden-Württemberg
Germany	Novartis Investigational Site Nr. 90	Erfurt	Thuringia
Germany	Novartis Investigational Site Nr. 72	Hamburg
Germany	Novartis Investigational Site Nr. 79	Heiligenhaus	North Rhine-Westphalia
Germany	Novartis Investigational Site Nr. 88	Itzenhoe	Schleswig-Holstein
Germany	Novartis Investigational Site Nr. 89	Itzenhoe	Schleswig-Holstein
Germany	Novartis Investigational Site Nr. 62	Kehl	Baden-Württemberg
Germany	Novartis Investigational Site Nr. 80	Kleve Materborn	North Rhine-Westphalia
Germany	Novartis Investigational Site Nr. 61	Mainz	Rhineland-Palatinate
Germany	Novartis Investigational Site Nr. 78	Monchengladbach	North Rhine-Westphalia
Germany	Novartis Investigational Site Nr. 82	Munster	North Rhine-Westphalia
Germany	Novartis Investigational Site Nr. 64	Oberstenfeld	Baden-Württemberg
Germany	Novartis Investigational Site Nr. 67	Schweigen	Rhineland-Palatinate
Germany	Novartis Investigational Site Nr. 87	Stockelsdorf	Schleswig-Holstein
Germany	Novartis Investigational Site Nr. 86	Wanzleben	Saxony-Anhalt
Germany	Novartis Investigational Site Nr. 83	Warburg	North Rhine-Westphalia
Germany	Novartis Investigational Site Nr. 66	Welzheim	Baden-Württemberg
Italy	Novartis Investigational Site Nr. 7	Firenze	Tuscany
Italy	Novartis Investigational Site Nr. 5	Milano	Lombardy
Italy	Novartis Investigational Site Nr. 52	Milano	Lombardy
Italy	Novartis Investigational Site Nr. 6	Novara	Piedmont
Italy	Novartis Investigational Site Nr. 9	Padova	Veneto
Spain	Novartis Investigational Site Nr. 11	Almassora	Castellón
Spain	Novartis Investigational Site Nr. 10	Castellon de la Plana	Castellón
Spain	Novartis Investigational Site Nr. 25	Catarroja	Valencia
Spain	Novartis Investigational Site Nr. 21	La Eliana	Valencia
Spain	Novartis Investigational Site Nr. 49	Oviedo	Asturias
Spain	Novartis Investigational Site 14	Sagunto	Valencia
Spain	Novartis Investigational Site Nr. 46	Santiago de Compostela	A Coruña
Spain	Novartis Investigational Site Nr. 15	Valencia
Spain	Novartis Investigational Site Nr. 16	Valencia
Spain	Novartis Investigational Site Nr. 17	Valencia
Spain	Novartis Investigational Site Nr. 18	Valencia
Spain	Novartis Investigational Site Nr. 19	Valencia
Spain	Novartis Investigational Site Nr. 23	Valencia
Spain	Novartis Investigational Site Nr. 24	Valencia
Spain	Novartis Investigational Site Nr. 12	Vall D'Uixo	Castelló
Spain	Novartis Investigational Site Nr. 48	Vigo Pontevedra	Pontevedra
United Kingdom	Novartis Investigational Site 3	Bristol	South West England
United Kingdom	Novartis Investigational Site Nr. 4	Exeter	South West England
United Kingdom	Novartis Investigational Site Nr. 2	London
United Kingdom	Novartis Investigational Site Nr. 1	Oxford	South East England

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Serum Bactericidal Activity =1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine	The percentage of subjects with serum bactericidal activity(hSBA)titer =1:5 after receiving three doses of rMenB+OMV NZ vaccine were evaluated to demonstrate sufficient immune response following rMenB+OMV NZ vaccination, when given concomitantly with routine infant vaccines to healthy infants.; The serum bactericidal antibodies directed against serogroup B meningococci, are measured by human complement Serum Bactericidal Assay (hSBA).; The immune response was considered sufficient for groups B+R246 and B+R234 if the lower limit of the 2-sided 95% confidence interval was = 70% for all three strains.	One month after third Men B vaccination	No
Primary	Safety and Tolerability of 3 Doses of rMenB - Concomitantly With Routine Infant Vaccines at 2, 4 and 6 Months of Age - Concomitantly With Routine Vaccines at 2, 3 and 4 Months of Age - Alone at 2, 4 and 6 Months of Age	Safety and Tolerability of 3 Doses of rMenB was assessed in terms of the number of subjects who reported solicited local and systemic adverse events when administered concomitantly with routine infant vaccines at 2,4,6 months of age (B+R246) to when rMenB+OMV NZ and routine vaccines were administered separately (group B246_R357).	10 months (groups 1 and 2); 8 months (groups 3 and 4)	No
Secondary	Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age	The non-inferiority of immune response to rMenB+OMV NZ vaccination when administered concomitantly with routine infant vaccines at 2,4,6 months of age(B+R246) to when rMenB+OMV NZ and routine vaccines were administered separately (group B246_R357)was assessed in terms of percentage of subjects With hSBA= 1:5.	One month after 3rd Men B vaccination	No
Secondary	Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine	Non-inferiority of immune response to routine vaccine antigens when routine vaccines were administered concomitantly with rMenB+OMV NZ vaccine [group B+R234] to when only routine vaccines were given [Group R234] were assessed in terms of percentage of subjects with antibody concentrations =0.1 IU/mL against Diphtheria and Tetanus antigens as measured by enzyme-linked immunosorbent assay.	One month after 3rd vaccination	No
Secondary	Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines.	The hSBA antibody titers when rMenB+OMV NZ vaccine is administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately are reported in terms of vaccine-group-specific geometric mean titers.	One month after third Men B vaccination	No
Secondary	Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines.	The geometric mean ratio(GMR) of GMTs at 1 month after 3rd rMenB+OMV NZ vaccination to prevaccination GMTs, when rMenB+OMV NZ was administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately.	one month after third Men B vaccination	No
Secondary	Percentage of Subjects With hSBA =1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine.	The percentage of subjects with hSBA titers =1:8, following rMenB+OMV NZ vaccination when given concomitantly with routine infant vaccines to when rMenB+OMV NZ and routine vaccines were given separately.	One month after third Men B vaccination	No
Secondary	Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines.	The percentage of subjects with 4-fold rise in hSBA titers at 1 month after 3rd rMenB+OMV NZ vaccination from baseline, when rMenB+OMV NZ was administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately.	One month after third Men B vaccination	No
Secondary	Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine.	Non-inferiority of immune response to routine vaccine antigens when routine vaccines were administered concomitantly with rMenB+OMV NZ vaccine [group B+R234] to when only routine vaccines were given [Group R234] were assessed in terms of percentage of subjects achieving seroconversion for pertussis antigens - Filamentous Hemagglutinin (FHA), Pertactin and Pertussis Toxoid (PT) at 1 month after 3rd vaccination versus baseline.; Seroconversion was defined as a 4-fold increase for each pertussis antigen or in those initially seropositive, persistence of the pre-vaccination antibody concentration at least at the same antibody concentration as before vaccination, taking into account the decay of maternal antibodies.	1 month after 3rd vaccination	No