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

A Phase 3, Open-Label, Randomized, Multi-Center Study to Evaluate the Safety and Immunogenicity After One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine Administered to Healthy Infants and Toddlers

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).

Study Overview

• Status: Completed
• Conditions: Meningococcal Meningitis
• Intervention / Treatment: Biological: MenACWY-CRM197 (two doses); Biological: PCV7; Biological: DTPa-IPV-HepB-Hib; Biological: MenACWY-CRM197 (one dose); Biological: MenC

• Study Type: Interventional
• Enrollment (Actual): 662
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bad Kreuznach, Germany, 55543
    • Site 22
  • Bad Lobenstein, Germany, 07356
    • Site 38
  • Balve, Germany, 58802
    • Site 24
  • Berlin, Germany, 12589
    • Site 3
  • Berlin, Germany, 12619
    • Site 27
  • Berlin, Germany, 12627
    • Site 20
  • Berlin, Germany, 12627
    • Site 26
  • Berlin, Germany, 13189
    • Site 13
  • Berlin, Germany, 13189
    • Site 31
  • Berlin, Germany, 13347
    • Site 25
  • Bönnigheim, Germany, 74357
    • Site 15
  • Eschwege, Germany, 37269
    • Site 39
  • Flensburg, Germany, 24937
    • Site 32
  • Frankenthal, Germany, 67227
    • Site 16
  • Glücksburg, Germany, 24960
    • Site 33
  • Hamburg, Germany, 22147
    • Site 35
  • Kehl, Germany, 77694
    • Site 2
  • Mainz, Germany, 55127
    • Site 28
  • Mainz, Germany, 55131
    • Site 44
  • München-Ramersdorf, Germany, 81669
    • Site 43
  • Neuhaus am Rennweg, Germany, 98724
    • Site 42
  • Neumünster, Germany, 24534
    • Site 21
  • Neumünster, Germany, 24534
    • Site 9
  • Oberstenfeld, Germany, 71720
    • Site 10
  • Stuttgart, Germany, 70193
    • Site 4
  • Stuttgart, Germany, 70469
    • Site 19
  • Weilheim i OB, Germany, 82362
    • Site 30
  • Wiesloch, Germany, 69168
    • Site 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MenACWY-CRM197 (2 doses) + Concomitant Vaccines; 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.	Biological: MenACWY-CRM197 (two doses); Two 0.5mL doses of MenACWY conjugate vaccine (MenACWY-CRM197) was administered by intramuscular injection.; Biological: PCV7; One 0.5mL dose of Pneumococcal 7-valent Conjugate Vaccine (PCV7) was administered by intramuscular injection.; Biological: DTPa-IPV-HepB-Hib; One 0.5mL dose of Combined Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b (DTPa-IPV-HepB-Hib) vaccine was administered by intramuscular injection.
Experimental: MenACWY-CRM197 (1 dose) + Concomitant Vaccines; 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.	Biological: PCV7; One 0.5mL dose of Pneumococcal 7-valent Conjugate Vaccine (PCV7) was administered by intramuscular injection.; Biological: DTPa-IPV-HepB-Hib; One 0.5mL dose of Combined Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b (DTPa-IPV-HepB-Hib) vaccine was administered by intramuscular injection.; Biological: MenACWY-CRM197 (one dose); One 0.5mL dose of MenACWY conjugate vaccine (MenACWY-CRM197) was administered by intramuscular injection.
Active Comparator: MenC (1 dose) + Concomitant Vaccines; 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.	Biological: PCV7; One 0.5mL dose of Pneumococcal 7-valent Conjugate Vaccine (PCV7) was administered by intramuscular injection.; Biological: DTPa-IPV-HepB-Hib; One 0.5mL dose of Combined Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b (DTPa-IPV-HepB-Hib) vaccine was administered by intramuscular injection.; Biological: MenC; One 0.5mL dose of MenC vaccine was administered by intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Serum Bactericidal Titer ≥ 1:8 Against N.Meningitidis Serogroup C	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.	1 month postvaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:4 Against N.Meningitidis Serogroup C	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.	1 month postvaccination
Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, C, W, Y	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.; 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.	1 month postvaccination.
Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, W, Y	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.	1 month postvaccination.
Human Serum Bactericidal Activity Geometric Mean Titers After One Dose of MenACWY-CRM197 and MenC Against N.Meningitidis Serogroup C	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.	1 month postvaccination
Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, W, Y	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.	1 month postvaccination
Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, C, W, Y	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.; 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.	1 month postvaccination
Percentages of Subjects With Seroresponse Rates After One Dose of DTPa-IPV-HepB-Hib (Concomitant Vaccine)	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.	1 month postvaccination
Percentages of Subjects With Seroresponse Rates After One Dose of PCV7 (Concomitant Vaccine)	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.	1 month postvaccination
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	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).	1 month postvaccination and 6-18 months postvaccination.
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	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).	1 month postvaccination 6-18 months postvaccination
Persistence of Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup C	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).	1 month postvaccination and 6-18 months postvaccination.
Persistence of Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, W, Y	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).	6-18 months postvaccination.
Percentages of Subjects With Rabbit Serum Bactericidal ≥ 1:8, ≥ 1:128 and Four Fold Rise Against N.Meningitidis Serogroup C	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.; 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.	1 month postvaccination.
Percentages of Subjects With Rabbit Serum Bactericidal ≥ 1:8, ≥ 1:128, and Four Fold Rise Against N.Meningitidis Serogroup A, W, Y	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.; 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.	1 month postvaccination.
Rabbit Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup C	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.; 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.	1 month postvaccination.
Rabbit Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup A, W, Y	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.; 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.	1 month postvaccination.
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 to Day 7 Postvaccination), After Any Vaccination	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	From day 1 to day 7 postvaccination

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Giuliani MM, Biolchi A, Keshavan P, Moriondo M, Tomei S, Santini L, Mori E, Brozzi A, Bodini M, Nieddu F, Ricci S, Mzolo T, Costantini M, Azzari C, Pellegrini M. Bactericidal antibodies against hypervirulent Neisseria meningitidis C field strains following MenC-CRM or MenACWY-CRM priming and MenACWY-CRM booster in children. Hum Vaccin Immunother. 2021 May 4;17(5):1442-1449. doi: 10.1080/21645515.2020.1833578. Epub 2020 Dec 16.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: April 24, 2008
• First Submitted That Met QC Criteria: April 25, 2008
• First Posted (Estimate): April 28, 2008

Study Record Updates

• Last Update Posted (Estimate): November 7, 2013
• Last Update Submitted That Met QC Criteria: September 3, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Meningitis; Infants; Toddlers; Conjugate Vaccine; Meningococcal; ACWY; Concomitant Vaccination
• 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
• Other Study ID Numbers: V59P22; 2007-004754-82