Safety and Immunogenicity Evaluation After One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants and Toddlers

Phase 3

Completed

Conditions: Meningococcal Meningitis

Interventions: Biological: MenACWY-CRM197 (two doses)
Biological: MenC
Biological: PCV7
Biological: DTPa-IPV-HepB-Hib
Biological: MenACWY-CRM197 (one dose)

Registration Number: NCT00667602

Lead Sponsor: Novartis Vaccines

Brief Summary: The primary immunogenicity objective is to assess and compare the immunogenicity of one dose of MenACWY to one dose of Menjugate given to healthy toddlers at 12 months of age as measured by the percentage of subjects with serum bactericidal titers directed against N. meningitidis serogroup C ≥ 1:8 obtained in the serum bactericidal assay using human complement (hSBA).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 662

Inclusion Criteria

infants 6 to 8 months old inclusive, who were born after full term pregnancy and previously received three doses of both Prevenar and Infanrix-hexa vaccines at least 30 days before study entry

Exclusion Criteria

who previously received any meningococcal vaccine;
who have had a previous confirmed or suspected disease caused by N. meningitidis, C. diphtheriae, C. tetani, Poliovirus, Hepatitis B, Hib, Pneumococcus or B. pertussis;
who have had household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis (serogroups A, C, W135, or Y), B. pertussis, Hib, C. diphtheriae, Polio, or pneumococcal infection at any time since birth;
Subjects with any serious, acute or chronic progressive disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MenACWY-CRM197 (2 doses) + Concomitant Vaccines	MenACWY-CRM197 (two doses)	Infants received two doses of MenACWY-CRM197 at 6 to 8 and 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months.
MenACWY-CRM197 (2 doses) + Concomitant Vaccines	PCV7	Infants received two doses of MenACWY-CRM197 at 6 to 8 and 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months.
MenACWY-CRM197 (2 doses) + Concomitant Vaccines	DTPa-IPV-HepB-Hib	Infants received two doses of MenACWY-CRM197 at 6 to 8 and 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months.
MenACWY-CRM197 (1 dose) + Concomitant Vaccines	PCV7	Infants received one dose of MenACWY-CRM197 at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age.
MenACWY-CRM197 (1 dose) + Concomitant Vaccines	DTPa-IPV-HepB-Hib	Infants received one dose of MenACWY-CRM197 at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age.
MenACWY-CRM197 (1 dose) + Concomitant Vaccines	MenACWY-CRM197 (one dose)	Infants received one dose of MenACWY-CRM197 at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age.
MenC (1 dose) + Concomitant Vaccines	MenC	Infants received one dose of MenC vaccine at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age.
MenC (1 dose) + Concomitant Vaccines	PCV7	Infants received one dose of MenC vaccine at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age.
MenC (1 dose) + Concomitant Vaccines	DTPa-IPV-HepB-Hib	Infants received one dose of MenC vaccine at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age.

Primary Outcome Measures

Name	Time	Method
Percentages of Subjects With Serum Bactericidal Titer ≥ 1:8 Against N.Meningitidis Serogroup C	1 month postvaccination	Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was measured using serum bactericidal assay with human complement (hSBA) titer ≥ 1:8 against N.meningitidis serogroup C.

Secondary Outcome Measures

Name	Time	Method
Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:4 Against N.Meningitidis Serogroup C	1 month postvaccination	Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentage of subjects with serum bactericidal activity using human complement (hSBA) titers ≥ 1:4 against N. meningitidis serogroup C.
Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, C, W, Y	1 month postvaccination.	1. Immunogenicity of two doses of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month postvaccination was assessed and compared as percentages of subjects with serum bactericidal titer with human complement (hSBA) ≥ 1:8, ≥ 1:4 against N.meningitidis Serogroup C. 2. Immunogenicity of two doses of MenACWY-CRM197 vaccine one month postvaccination was assessed as percentages of subjects with serum bactericidal titer with human complement (hSBA) ≥ 1:8, ≥ 1:4 against N.meningitidis Serogroup A, W, Y.
Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, W, Y	1 month postvaccination.	Immunogenicity for one dose of MenACWY was assessed as percentages of subjects with serum bactericidal titer with human complement (hSBA) ≥ 1:8 and titer ≥ 1:4 by serogroups A, W, Y. Serogroup C is not shown here as it is shown in other outcome measures.
Human Serum Bactericidal Activity Geometric Mean Titers After One Dose of MenACWY-CRM197 and MenC Against N.Meningitidis Serogroup C	1 month postvaccination	Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed with geometric mean titer (GMT) of serum bactericidal assay with human complement (hSBA) against N. meningitidis serogroup C.
Persistence of Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup C	1 month postvaccination and 6-18 months postvaccination.	Persistence of immunogenicity of either one or two doses of MenACWY or one dose of MenC as measured by human serum bactericidal activity geometric mean titers directed against N.meningitidis serogroup C (only for subjects enrolled in Australia).
Persistence of Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, W, Y	6-18 months postvaccination.	Immunogenicity of two doses of MenACWY to one dose of MenACWY as measured by hSBA GMTs directed against N.meningitidis serogroups A, W, Y (only for subjects enrolled in Australia).
Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, W, Y	1 month postvaccination	Immunogenicity of one dose of MenACWY-CRM197 one month postvaccination was assessed with GMT of serum bactericidal assay with hSBA against Serogroups A, W, Y.
Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, C, W, Y	1 month postvaccination	1. The immunogenicity of two doses of MenACWY-CRM197, to a single dose of MenC was assessed and compared as measured by human Serum Bactericidal Activity Geometric Mean Titers directed against N. meningitidis serogroup C. 2. The immunogenicity of two doses of MenACWY-CRM197, to a single dose of MenC was assessed as measured by human Serum Bactericidal Activity Geometric Mean Titers directed against N. meningitidis serogroups A, W, Y.
Percentages of Subjects With Seroresponse Rates After One Dose of DTPa-IPV-HepB-Hib (Concomitant Vaccine)	1 month postvaccination	The immunogenicity of one dose of MenC to one dose of DTPa-IPV-HepB-Hib concomitant vacccine was assessed. For Pertussis antigens, Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN), the seroresponse in initially seronegative subjects (pre-vaccination antibody concentration \< LLQ) is defined as post-vaccination antibody concentration \>= LLQ; in initially seropositive subjects (pre-vaccination antibody concentration \>=LLQ) seroresponse is defined as at least two fold increase of the pre-vaccination antibody concentration. Diptheria and Tetanus: primary endpoint ELISA (Enzyme-linked immunosorbent assay) \>=0.1 (international unit -IU) IU/mL and the secondary endpoint is ELISA\>=1.0 IU/mL. Polio type 1, 2 and 3: bNT (neutralization test) with \>=1:8. HepB (HBV): primary endpoint ELISA \>=10mU/mL. PRP-T: primary endpoint ≥ 0.15 mcg/mL and ≥ 1.00 mcg/mL.
Percentages of Subjects With Seroresponse Rates After One Dose of PCV7 (Concomitant Vaccine)	1 month postvaccination	To compare the immunogenicity of PCV7 (Pneumococcal 7-valent Conjugate)Vaccine when given concomitantly with one dose or two doses of MenACWY-CRM197 or with MenC to infants at 12 months of age. Seroresponse for PCV7 (PnC 4, PnC 6B, PnC 9V, PnC 14, PnC 18C, PnC 19F, PnC 23F) is defined as: a subject with primary endpoint ELISA ≥ 0.35 mcg/mL and secondary endpoint ELISA ≥ 1.0 mcg/mL.
Persistence of Immune Response Measured as Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroup C	1 month postvaccination and 6-18 months postvaccination.	Persistence of immune response to either one or two doses of MenACWY-CRM197 or one dose of MenC as measured by serum bactericidal assay with human complement (hSBA) titers ≥ 1:8, and titers ≥ 1:4 directed against N.meningitidis serogroup C (only for subjects enrolled in Australia).
Persistence of Immune Response Measured as Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 ,and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, W, Y	1 month postvaccination 6-18 months postvaccination	Persistence of immune response to either one or two doses of MenACWY-CRM197 or one dose of MenC as measured by serum bactericidal assay with human complement (hSBA) titer ≥ 1:8 and titer ≥ 1:4 directed against N. meningitidis serogroups A, W and Y (only for subjects enrolled in Australia).
Percentages of Subjects With Rabbit Serum Bactericidal ≥ 1:8, ≥ 1:128 and Four Fold Rise Against N.Meningitidis Serogroup C	1 month postvaccination.	1. Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup C. 2. Immunogenicity of two doses of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup C.
Percentages of Subjects With Rabbit Serum Bactericidal ≥ 1:8, ≥ 1:128, and Four Fold Rise Against N.Meningitidis Serogroup A, W, Y	1 month postvaccination.	1. Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup A, W, Y. 2. Immunogenicity of two doses of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup A, W, Y.
Rabbit Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup C	1 month postvaccination.	1. Immunogenicity of one dose of MenACWY-CRM197 to one dose of MenC vaccine at 12 months of age was assessed with geometric mean titer (GMT) of serum bactericidal assay with rabbit complement (rSBA) against Serogroup C. 2. Immunogenicity of two doses of MenACWY-CRM197 to one dose of MenC vaccine at 6 to 8 and 12 months of age was assessed with geometric mean titer (GMT) of serum bactericidal assay with rabbit complement (rSBA) against Serogroup C.
Rabbit Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup A, W, Y	1 month postvaccination.	1. Immunogenicity of one dose of MenACWY-CRM197 to one dose of MenC vaccine at 12 months of age was assessed with GMT of SBA with rabbit complement (rSBA) against Serogroup A, W, Y. 2. Immunogenicity of two doses of MenACWY-CRM197 to one dose of MenC vaccine at 6 to 8 and 12 months of age was assessed with geometric mean titer (GMT) of serum bactericidal assay with rabbit complement (rSBA) against Serogroup A, W, Y.
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 to Day 7 Postvaccination), After Any Vaccination	From day 1 to day 7 postvaccination	Safety was assessed as the number of subjects who reported solicited local reactions from day 1 to day 7 postvaccination for all the three vaccination groups. safety was assessed as the number of subjects who reported solicited systemic reactions from day 1 to day 7 Following the Month 12 vaccination in all three vaccination groups

Trial Locations

Locations (28): Site 38
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Bad Lobenstein, Germany
Site 24
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Balve, Germany
Site 4
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Stuttgart, Germany
Site 44
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Mainz, Germany
Site 22
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Bad Kreuznach, Germany
Site 13
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Berlin, Germany
Site 31
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Berlin, Germany
Site 30
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Weilheim i OB, Germany
Site 3
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Berlin, Germany
Site 27
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Berlin, Germany
Site 35
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Hamburg, Germany
Site 16
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Frankenthal, Germany
Site 33
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Glücksburg, Germany
Site 2
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Kehl, Germany
Site 28
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Mainz, Germany
Site 20
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Berlin, Germany
Site 26
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Berlin, Germany
Site 25
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Berlin, Germany
Site 15
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Bönnigheim, Germany
Site 42
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Neuhaus am Rennweg, Germany
Site 43
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München-Ramersdorf, Germany
Site 21
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Neumünster, Germany
Site 10
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Oberstenfeld, Germany
Site 9
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Neumünster, Germany
Site 19
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Stuttgart, Germany
Site 6
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Wiesloch, Germany
Site 39
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Eschwege, Germany
Site 32
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Flensburg, Germany