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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00667602
First received: April 24, 2008
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

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).


Condition Intervention Phase
Meningococcal Meningitis
Biological: MenACWY-CRM197 (two doses)
Biological: MenC
Biological: PCV7
Biological: DTPa-IPV-HepB-Hib
Biological: MenACWY-CRM197 (one dose)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentages of Subjects With Serum Bactericidal Titer ≥ 1:8 Against N.Meningitidis Serogroup C [ Time Frame: 1 month postvaccination ] [ Designated as safety issue: No ]
    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:
  • Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:4 Against N.Meningitidis Serogroup C [ Time Frame: 1 month postvaccination ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month postvaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month postvaccination. ] [ Designated as safety issue: No ]

    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 [ Time Frame: 1 month postvaccination ] [ Designated as safety issue: No ]
    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.

  • Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, W, Y [ Time Frame: 1 month postvaccination ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month postvaccination ] [ Designated as safety issue: No ]
    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) [ Time Frame: 1 month postvaccination ] [ Designated as safety issue: No ]

    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) [ Time Frame: 1 month postvaccination ] [ Designated as safety issue: No ]

    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 [ Time Frame: 1 month postvaccination and 6-18 months postvaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month postvaccination 6-18 months postvaccination ] [ Designated as safety issue: No ]
    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).

  • Persistence of Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup C [ Time Frame: 1 month postvaccination and 6-18 months postvaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-18 months postvaccination. ] [ Designated as safety issue: No ]
    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).

  • Percentages of Subjects With Rabbit Serum Bactericidal ≥ 1:8, ≥ 1:128 and Four Fold Rise Against N.Meningitidis Serogroup C [ Time Frame: 1 month postvaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month postvaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month postvaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 month postvaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From day 1 to day 7 postvaccination ] [ Designated as safety issue: Yes ]

    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



Enrollment: 662
Study Start Date: March 2008
Study Completion Date: October 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: MenC
One 0.5mL dose of MenC vaccine 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.

  Eligibility

Ages Eligible for Study:   6 Months to 8 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00667602

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

No publications provided

Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT00667602     History of Changes
Other Study ID Numbers: V59P22, 2007-004754-82
Study First Received: April 24, 2008
Results First Received: February 18, 2013
Last Updated: September 3, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut

Keywords provided by Novartis:
Meningococcal
ACWY
Conjugate Vaccine
Meningitis
Toddlers
Infants
Concomitant Vaccination

Additional relevant MeSH terms:
Meningitis
Meningitis, Meningococcal
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Bacterial
Central Nervous System Bacterial Infections
Bacterial Infections
Meningococcal Infections
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Pentetic Acid
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antidotes
Protective Agents
Physiological Effects of Drugs
Iron Chelating Agents

ClinicalTrials.gov processed this record on April 16, 2014