Immunogenicity, Safety and Lot to Lot Consistency of Novartis Meningococcal B Recombinant Vaccine When Administered With Routine Infant Vaccinations to Healthy Infants

A Phase 3, Partially Blinded, Randomized, Multi-Center, Controlled Study to Evaluate Immunogenicity, Safety and Lot to Lot Consistency of Novartis Meningococcal B Recombinant Vaccine When Administered With Routine Infant Vaccinations to Healthy Infants

The proposed study was aimed to assess the immunogenicity, safety, tolerability and lot to lot consistency of 3 lots of Novartis Meningococcal B vaccine when given concomitantly with routine infant vaccines.

Study Overview

• Status: Completed
• Conditions: Serogroup B Meningococcal Meningitis
• Intervention / Treatment: Biological: Serogroup B meningococcal Vaccine lot 1 (rMenB Lot 1); Biological: Serogroup B meningococcal Vaccine lot 2 (rMenB Lot 2); Biological: Serogroup B meningococcal Vaccine lot 3 (rMenB Lot 3); Biological: Infanrix Hexa; Biological: Prevenar; Biological: Menjugate

• Study Type: Interventional
• Enrollment (Actual): 3630
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Hall in Tirol, Austria, 6060
    • Grässl
  • Kirchdorf, Austria, 4560
    • Häckel
  • Neufeld a.d. Leitha, Austria, 2491
    • Prieler
  • Salzburg, Austria, 5020
    • Maurer
  • Wels, Austria, 4600
    • Angermayr
  • Wien, Austria, 1230
    • Sommer
• Czechia
  • Boskovice, Czechia, 680 01
    • Site 27
  • Brno, Czechia, 628 00
    • Site 19
  • Chomutov, Czechia, 430 03
    • Site 22
  • Děčín, Czechia, 405 01
    • Site 14
  • Havlíčkův Brod, Czechia, 580 22
    • Site 12
  • Hradec Králové, Czechia, 500 01
    • Site 8
  • Hradec Králové, Czechia, 500 05
    • Site 9
  • Hranice I-mesto, Czechia, 753 01
    • Site 28
  • Humpolec, Czechia, 396 01
    • Site 13
  • Jindřichův Hradec, Czechia, 377 01
    • Site 15
  • Kladno 2, Czechia, 272 00
    • Site 25
  • Kolín, Czechia, 280 02
    • Site 21
  • Liberec, Czechia, 460 15
    • Site 10
  • Litomerice, Czechia, 412 01
    • Site 24
  • Ostrava, Czechia, 702 00
    • Site 17
  • Ostrava-Poruba, Czechia, 708 68
    • Site 18
  • Pardubice, Czechia, 532 03
    • Site 7
  • Plzeň, Czechia, 305 99
    • Site 16
  • Prague, Czechia, 130 00
    • Site 2
  • Prague, Czechia, 140 00
    • Site 3
  • Prague, Czechia, 16000
    • Site 5
  • Prague, Czechia, 19000
    • Site 6
  • Rumburk, Czechia, 408 01
    • Site 26
  • Usti nad Labem, Czechia, 400 01
    • Site 23
  • Znojmo, Czechia, 669 00
    • Site 20
  • Červený Kostelec, Czechia, 54941
    • Site11
• Finland
  • Espoo, Finland, 02230
    • Site 30
  • Helsinki, Finland, 00100
    • Site 31
  • Helsinki, Finland, 00930
    • Site 32
  • Järvenpää, Finland, 04400
    • Site 34
  • Kokkola, Finland, 67100
    • Site 35
  • Kotka, Finland, 48600
    • Site 45
  • Kuopio, Finland, 70211
    • Site 46
  • Lahti, Finland, 15140
    • Site 47
  • Oulu, Finland, 90220
    • Site 49
  • Pori, Finland, 28100
    • Site 50
  • Seinäjoki, Finland, 60100
    • Site 51
  • Tampere, Finland, 33100
    • Site 52
  • Turku, Finland, 20520
    • Site 53
  • Vantaa, Finland, 01300
    • Site 33
  • Vantaa, Finland, 01600
    • Site 48
• Germany
  • Detmold, Germany, 32756
    • Site 99
  • Espelkamp, Germany, 32339
    • Site 92
  • Freising, Germany, 85354
    • Site 95
  • Fulda, Germany, 36037
    • Site 64
  • Lauffen, Germany, 74348
    • Site 58
  • Marbach a. N., Germany, 74348
    • Site 57
  • München, Germany, 81377
    • Site 97
  • München, Germany, 81475
    • Site 96
  • Műnchen, Germany, 81737
    • Site 91
  • Porta Westfalica, Germany, 32457
    • Site 81
  • Schwieberdingen, Germany, 71701
    • Site 65
  • Weilheim, Germany, 82362
    • Site 94
• Italy
  • Genova, Italy, 16132
    • Dipartimento di Scienze della Salute
  • Messina, Italy, 98122
    • Università degli Studi di Messina - Pad. NI - A.O.U. Policlinico G. Martino
  • Milano, Italy, 20122
    • Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena Italia
  • Milano, Italy, 20157
    • Pediatria dell' Ospedale Sacco
  • Novara, Italy, 28100
    • Ospedale Maggiore della Carita'-Clinica Pediatrica
  • Sassari, Italy, 07100
    • Istituto di Igiene e Medicina Preventiva - Università degli Studi di Sassari
  • Taranto, Italy, 74100
    • ASL/TA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy 2-month old infants (55-89 days, inclusive)

Exclusion Criteria:

• 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;
• Any serious chronic or progressive disease
• Known or suspected impairment or alteration of the immune system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rMenB Lot1; Subjects received one injection of rMenB+OMV NZ (Lot 1) at 2, 4, 6 months of age concomitantly with the routinely administered infant vaccines.	Biological: Serogroup B meningococcal Vaccine lot 1 (rMenB Lot 1); One dose of rMenB Lot concomitantly with the routinely administered infant vaccines
Experimental: rMenB Lot2; Subjects received one injection of rMenB+OMV NZ (Lot 2) at 2, 4, 6 months of age concomitantly with the routinely administered infant vaccines.	Biological: Serogroup B meningococcal Vaccine lot 2 (rMenB Lot 2); One dose of rMenB concomitantly with the routinely administered infant vaccines
Experimental: rMenB Lot3; Subjects received one injection of rMenB+OMV NZ (Lot 3) at 2, 4, 6 months of age concomitantly with the routinely administered infant vaccines.	Biological: Serogroup B meningococcal Vaccine lot 3 (rMenB Lot 3); One dose of rMenB concomitantly with the routinely administered infant vaccines
Active Comparator: Routine; Subjects received the routinely administered infant vaccines at 2, 4, 6 months of age.	Biological: Infanrix Hexa; Routine vaccination; Biological: Prevenar; Routine vaccination
Active Comparator: MenC + Routine; Subjects received the routinely administered infant vaccines and Men C vaccine at 2, 4 and 6 months of age.	Biological: Infanrix Hexa; Routine vaccination; Biological: Prevenar; Routine vaccination; Biological: Menjugate; One dose of the routinely administered infant vaccines + MenC vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Geometric Mean Human Serum Bactericidal Activity (hSBA) Titers After Three Doses of rMenB+OMV NZ Vaccination	The hSBA antibody titer responses, one month after receiving the third vaccination of rMenB+OMV NZ vaccination, are reported as geometric mean titers (GMTs).	one month after the third vaccination
The Percentages of Subjects With hSBA Titer ≥1:5 After Receiving Three Doses of rMenB+OMV Vaccination (3 Lots Combined)	The immunogenicity was assessed in terms of the percentages of subjects who had received the three doses of rMenB+OMV NZ (3 lots combined) given concomitantly with routine infant vaccinations and percentages of subjects who received only the routine infant vaccinations as measured by hSBA titer ≥1:5 following rMenB+OMV NZ vaccinations one month after the third vaccination is reported.	one month after the third vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentages of Subjects With hSBA Titer ≥1:5 After Receiving Three Doses of rMenB+OMV Vaccination (From 3 Lots)	The immunogenicity was evaluated to assess the consistency of the immune response from three lots of rMenB+OMV NZ in terms of percentage of subjects as measured by hSBA titer ≥1:5 when given to healthy infants at 2, 4, and 6 months of age, at 1 month after the third vaccination.	1 month after the third vaccination
Geometric Mean Human Serum Bactericidal Activity Titers After the Routine Vaccination Without rMenB OMV NZ	The immunogenicity was assessed in terms of prevalence of meningococcal B antibodies as measured by the hSBA, at baseline and at one month after the third vaccination, in the subjects that received routine infant vaccines without rMenB+OMV NZ.	1 Month after the third vaccination
Geometric Mean Concentrations After Three Doses of rMenB+OMV NZ Vaccination (Against the 287-953 Antigen)	The immunogenicity was evaluated to characterize the immune response against vaccine antigen 287-953, as measured by ELISA at one month after third vaccination.	1 month after third vaccination
Geometric Mean Concentrations for Antigens (Pertussis Components) for the Routine Vaccinations	Immunogenicity of the pertussis components (PT, FHA, pertactin) of DTPa-HBV-IPV when given concomitantly with rMenB and PCV7 would be considered non-inferior to that of the routine vaccines given alone if the lower limit of the two-sided CI for the ratio of GMCs one month after third vaccination.	1 month after third vaccination
Percentages of Subjects With Antibody Response Against the Routine Antigens	The immunogenicity of routine infant vaccines when given concomitantly with rMenB+OMV NZ at 2, 4, and 6 months of age and of the routine infant vaccines given without rMenB+OMV NZ at 1 month after third vaccination with B pertussis, diptheria and tetanus toxoid, H influenza type b, Hepatitis B antigens was measured by ELISA (Enzyme-linked immunosorbent assay) and for polio type 1, type 2 and type 3 by neutralization test (NT)(>=1:8). Diptheria and Tetanus: primary endpoint ELISA >=0.1 (international unit -IU) IU/mL and the secondary endpoint is ELISA>=1.0 IU/mL. HepB (HBV):primary endpoint ELISA >=10 mU/mL. PRP-T: primary endpoint ≥ 0.15 mcg/mL and ≥ 1.00 mcg/mL.PNC >=0.35 mcg/ml	1 Month after third vaccination
Percentages of Subjects With Fourfold Increase in Antibody Concentrations Against the Routine Antigens	Immunogenicity was assessed in terms of the percentages of subjects with fourfold increase in antibody concentrations against the routine pertussis antigens FHA (Filamentous Hemagglutinin), Pertactin and PT (Pertussis Toxoid).	5 months
Percentages of Subjects With Fourfold Rise in hSBA Titers After Three Doses of rMenB+OMV NZ Vaccination	Immunogenicity was assessed in terms of the percentages of subjects with fourfold rise in hSBA titers after the three doses of rMenB+OMV NZ (lot 1 or lot 2 or lot 3) vaccination at 2, 4 and 6 months of age.	1 Month after third vaccination
Percentage of Subjects With hSBA Titers ≥1:8	Immunogenicity was assessed in terms of the percentages of subjects achieving hSBA titers ≥1:8 at one month after third vaccination with rMenB (lot 1 or lot 2 or lot 3) against the three vaccine strains.	1 month after third vaccination
Number of Subjects Reporting Solicited Adverse Events After Receiving Three Doses of rMenB+OMV NZ Vaccine	The safety and tolerability of three doses of rMenB+OMV NZ when given concomitantly with routine infant vaccines at 2, 4 and 6 months of age was assessed by the number of subjects reporting solicited local and systemic adverse events.	upto 7 days after any vaccination

Collaborators and Investigators

• Sponsor: Novartis Vaccines
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Zafack JG, Bureau A, Skowronski DM, De Serres G. Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials. BMJ Open. 2019 May 19;9(5):e026953. doi: 10.1136/bmjopen-2018-026953.
• Vesikari T, Esposito S, Prymula R, Ypma E, Kohl I, Toneatto D, Dull P, Kimura A; EU Meningococcal B Infant Vaccine Study group. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. Lancet. 2013 Mar 9;381(9869):825-35. doi: 10.1016/S0140-6736(12)61961-8. Erratum In: Lancet. 2013 Mar 9;381(9869):804.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: April 2, 2008
• First Submitted That Met QC Criteria: April 11, 2008
• First Posted (Estimate): April 14, 2008

Study Record Updates

• Last Update Posted (Actual): October 10, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: prevention; vaccination; infant; Meningococcal disease
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Meningococcal Infections; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V72P13; EUDRACT 2007-007781-38