B Cell Response to a Primary and a Booster Course of the Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00488683
First received: June 19, 2007
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

This study is aimed to assess whether the frequency of meningococcal serogroup A, C, W-135 and Y specific memory B Cells, measured 1 month after a primary vaccination series of Novartis MenACWY vaccine, predicts the specific serum bactericidal activity using human complement (hSBA) of (respectively) serogroup A, C, W-135 and Y at 12 months of age


Condition Intervention Phase
Meningococcal Disease
Biological: MenACWY-CRM
Biological: DTaP-Hib-IPV
Biological: PCV
Biological: MMR
Biological: Hib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II, Single Center, Open-label, Randomized Study to Investigate Meningococcal Serogroup A, C, W-135 and Y Saccharide Specific B Cell Response to a Primary and a Booster Course of the Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Summary of Memory B Cells Per 2 x 105 LOC by Serogroup A, C, W-135 and Y [ Time Frame: 1 month after primary vaccination and immediately before third dose at 12 months of age ] [ Designated as safety issue: No ]

    The memory B cell response at one month after primary vaccinations (5 months of age) was defined as the mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells, measured in vitro by ELISpot assay per 2x100000 lymphocytes obtained from culture (LOC) of peripheral blood mononuclear cells (PBMC) circulating in blood incubated for 5.5 days in the presence of polyclonal B cell activators.

    Serogroup A, C, W-135 and Y geometric mean titers (GMTs) were measured by serum bactericidal assay using human complement (hSBA) at 12 months of age (before third dose).

    Correlation and linear regression coefficients were determined between memory B cells at 1 month after primary vaccinations with MenACWY-CRM (5 months of age) and hSBA titers at 12 months of age (before third dose) for the serogroups A, C, W-135 and Y.



Secondary Outcome Measures:
  • Memory B Cells by Serogroup A, C, W-135 and Y [ Time Frame: 1 month after primary vaccination and immediately before third dose ] [ Designated as safety issue: No ]

    Memory B cell response at 1 month after primary vaccination and immediately before third dose at 12 months of age was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    The meningococcal serogroup A, C, W-135 and Y specific IgG concentrations immediately before third dose at 12 months of age were measured by ELISA.


  • Memory B Cells Per 2x100000 by Serogroup A,C, W-135 and Y at One Month After Primary MenACWY-CRM Vaccination and Third MenACWY-CRM Vaccination [ Time Frame: 1 month after primary vaccination and 1 month after third vaccination ] [ Designated as safety issue: No ]

    Memory B cell response at 1 month after MenACWY-CRM primary and booster vaccinations was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    hSBA GMTs for the serogroup A, C, W-135 and Y were measured one month after the third MenACWY-CRM vaccination.

    The meningococcal serogroup A, C, W-135 and Y specific IgG concentrations one month after third MenACWY-CRM vaccination were measured by ELISA.


  • Memory B Cells 1 Month After Primary Vaccination and Rise From Pre-third Dose to 1 Month After Third Dose of MenACWY-CRM Vaccination [ Time Frame: 1 month after primary and pre-third and 1 month after third vaccination ] [ Designated as safety issue: No ]

    Memory B cell response at 1 month after MenACWY-CRM primary and third (booster) vaccination was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    The serogroup A, C, W-135 and Y specific IgG concentrations at 1 month after MenACWY-CRM booster were measured by ELISA.

    hSBA GMTs were measured by hSBA assay one month after MenACWY-CRM booster vaccination.

    The rise in serogroup specific IgG, memory B cells and hSBA was calculated by pre/post third dose geometric mean ratios, calculated by the difference in the log10 of the concentrations/titers measured at 13 months to the log10 of the concentrations at 12 months: i.e. rise = log10(x) at 13 months minus log10(x)at 12 months where x is the serogroup specific IgG or memory B cell concentrations or SBA titers.


  • Memory B Cells 1 Month After Primary Vaccination and 1 Week After Third Vaccination by Serogroup A, C, W-135 and Y [ Time Frame: One month after primary vaccination and 1 week after third vaccination ] [ Designated as safety issue: No ]

    Memory B cell response at 1 month after primary vaccination and at 1 week after third vaccination was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    Plasma B cell response at 1 week after vaccination was measured as the mean number of cells secreting antibodies specific for meningococcal serogroup A, C, W-135 and Y, measured by ELISpot assay, per 2x100000 PBMC.

    Serogroup A, C, W-135 and Y specific IgG were measured by ELISA and hSBA GMTs were measured at 1 week after third vaccination.


  • CRM197 Specific Memory B Cells 1 Month After Primary Vaccination and at 12 Months of Age and One Month After MenACWY-CRM Third Vaccination [ Time Frame: 5 months (B cells), 12 months and 13 months (B cells and IgG) of age ] [ Designated as safety issue: No ]

    CRM197 specific memory B cell response at each time point was measured as mean number of CRM197 specific memory B cells by ELISpot assay per 2x100000 LOC.

    CRM197 specific IgG concentration was measured by ELISA at 12 months of age and one month after MenACWY-CRM booster vaccination.


  • Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone [ Time Frame: Before and one month after booster vaccination ] [ Designated as safety issue: No ]
    Memory B cell response before and one month after MenACWY-CRM booster vaccination at 12 months of age was measured as mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells by ELISpot assay per 2x100000 LOC.

  • Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone [ Time Frame: Before and one month after booster vaccination ] [ Designated as safety issue: No ]
    hSBA GMTs were measured before and one month after MenACWY-CRM booster vaccination at 12 months of age.

  • Serogroups A, C, W-135 and Y Specific Memory B Cell Response in Children Lacking a hSBA Titer of ≥1:8 One Month After MenACWY-CRM Primary Vaccination [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]
    The memory B cell response in children lacking a hSBA titer ≥1:8 one month after MenACWY-CRM primary vaccination was calculated as the mean number of meningococcal serogroup specific memory B cells, measured by ELISpot assay per 2x100000 LOC.

  • Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination [ Time Frame: Day 0, 7, 14, 49, 90, and 120 after MenACWY-CRM vaccination at month 4 ] [ Designated as safety issue: No ]

    To assess the kinetics of serogroup A, C, W-135 and Y specific memory B cells, plasma B cells and IgG concentrations were measured on days 0, 7, 14, 49, 90, and 120 following vaccination with MenACWY-CRM vaccination at month 4 of the study.

    The memory B cell response at different timepoint was defined as the mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells, measured in vitro by ELISpot assay per 2x100000 lymphocytes obtained from culture (LOC) of peripheral blood mononuclear cells (PBMC) circulating in blood incubated for 5.5 days in the presence of polyclonal B cell activators in vitro.

    The B plasma cell response at each time point was defined as the mean number of cells secreting antibodies specific for meningococcal serogroup A, C, W-135 and Y, measured by ELISpot assay, per 2x100000 PBMC.


  • Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination [ Time Frame: Day 0, 7, 14, 30, 49, 90,120 after MenACWY-CRM vaccination at month 4 ] [ Designated as safety issue: No ]
    To assess the kinetics of serogroup A, C, W-135 and Y specific hSBA titers, the geometric mean titer was measured on day 0, 7, 14, 30, 49, 90, and 120 following vaccination with MenACWY-CRM vaccination at month 4 of the study.

  • Correlation and Linear Regression Coefficients Between Serogroup A, C, W-135 and Y Specific Memory B Cells 1 Month After MenACWY-CRM Primary Vaccination and IgG Concentration at Day 1 in the Serum of Mothers of Infants [ Time Frame: Day 1 (IgG) and one month after primary vaccination (B cells) ] [ Designated as safety issue: No ]
    The serogroup A, C, W-135 and Y specific IgG concentrations were measured in the serum of mothers at the time of their enrollment into the study (Day 1) by ELISA.

  • Linear Regression Coefficients (1) Between Serogroup A, C, W-135 and Y Memory B at 5 Months and hSBA Titers at 12 Months, (2) Between Serogroup A, C, W-135 and Y Memory B at 5 Months and IgG at 12 Months, After a 2-Dose Primary Course of MenACWY-CRM [ Time Frame: 1 month post primary vaccination (B cells) and 12 months (hSBA titers and IgG) ] [ Designated as safety issue: No ]
    Linear regression analysis between memory B cells at 5 months of age and hSBA titers and IgG at 12 months of age was performed with and without inclusion of demographic factors (subject's household smoking status, number of older children living in subject's household, attendance at daycare and total duration of breast feeding) in the model.

  • Linear Regression Coefficients (1) Between Serogroup A, C, W-135 and Y Memory B Cells at 5 Months and Rise in hSBA Titers, (2) Between Serogroup A, C, W-135 and Y Memory B Cells at 5 Months and Rise in IgG, After Third Dose of MenACWY-CRM at 12 Months [ Time Frame: 1 month post primary vaccination (B cells) and 12 months (hSBA titers and IgG) ] [ Designated as safety issue: No ]

    The rise in serogroup-specific hSBA and IgG was calculated by pre/post third dose geometric mean ratios, calculated by the difference in the log10 of the concentrations/titers measured at 13 months to the log10 of the concentrations at 12 months: i.e. rise = log10(x) at 13 months minus log10(x) at 12 months where x is the serogroup specific IgG or SBA titers.

    Linear regression analysis between memory B cells at 5 months of age and rise in hSBA titers or IgG at 12 months of age was performed with and without inclusion of demographic factors (subject's household smoking status, number of older children living in subject's household, attendance at daycare and total duration of breast feeding) in the model.


  • Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. [ Time Frame: 7 days post each MenACWY-CRM and routine infant vaccination ] [ Designated as safety issue: Yes ]
    Safety was assessed as the percentage of subjects who reported injection site local reactions during 7-day follow-up period after each MenACWY-CRM and routine infant vaccination administered as a primary course of vaccination.

  • Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations [ Time Frame: 7 days post vaccination at 2, 3, and 4 months of age ] [ Designated as safety issue: Yes ]
    Safety was assessed as the percentage of subjects who reported systemic reactions during 7-day follow-up period after MenACWY-CRM (2 and 4 months) and routine infant primary vaccinations (2, 3 and 4 months).

  • Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age [ Time Frame: 7 days post 12 month vaccination ] [ Designated as safety issue: Yes ]
    Safety was assessed as the percentage of subjects who reported injection site local reactions during 7-day follow-up period after MenACWY-CRM and PCV vaccinations at 12 months of age.

  • Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age [ Time Frame: 7 days post 12 months vaccination ] [ Designated as safety issue: Yes ]
    Safety was assessed as the percentage of subjects who reported systemic reactions during 7-day follow-up period after MenACWY-CRM and PCV vaccination at 12 months of age.

  • Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone [ Time Frame: Before and one month after booster vaccination ] [ Designated as safety issue: No ]
    Serogroup A, C, W-135 and Y specific IgG concentrations were measured before and one month after MenACWY-CRM booster vaccination by ELISA.

  • Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination [ Time Frame: Day 0, 7, 14, 30, 49, 90,120 after MenACWY-CRM vaccination at month 4 ] [ Designated as safety issue: No ]
    To assess the kinetics of serogroup A, C, W-135 and Y specific IgG concentrations, the geometric mean concentration was measured on day 0, 7, 14, 30, 49, 90, and 120 following vaccination with MenACWY-CRM vaccination at month 4 of the study.


Enrollment: 216
Study Start Date: July 2007
Study Completion Date: June 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MenACWY-CRM and Routine Vaccines (Group 1)
Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.
Biological: MenACWY-CRM
One dose (0.5 mL) of MenACWY conjugate vaccine supplied as an extemporaneous mixing just before injection of the lyophilized component (MenA) reconstituted with the liquid component (MenCWY) was administered at 2-, 4-, and 12-months as IM injections in the anterolateral area of the right thigh.
Biological: DTaP-Hib-IPV
IM injections of 3 doses of 0.5 mL each of DTaP-Hib-IPV supplied in prefilled vial were administered at 2-, 3-, and 4-months in the anterolateral area of the left thigh.
Other Name: Combined diphtheria, tetanus toxoid, acellular pertussis, Haemophilus influenzae type B and inactivated polio vaccine; Pediacel
Biological: PCV
IM injections of 3 doses of 0.5 mL each of PCV supplied in pre-filled syringe were administered at 2-, 4-, and 12-months (Groups 2 and 3) or 13-months (Group 1) in the anterolateral area of the left thigh.
Other Name: Heptavalent Streptoccus pneumonia; Prevnar
Biological: MMR
IM injection of one dose of 0.5 mL of MMR obtained by extemporaneous mixing just before injection of powder and the solvent for solution was administered at 13 months in the anterolateral area of the left thigh.
Other Name: Measles, mumps, and rubella vaccine; Priorix
Biological: Hib
IM injection of one dose 0.5 mL of Hib supplied in pre-filled syringe was administered at 13 months in the anterolateral area of the right thigh.
Other Name: Vaxem Hib
Experimental: MenACWY-CRM and Routine Vaccines (Group 2)

Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months.

This group had an additional blood draw at the time of enrollment.

Biological: MenACWY-CRM
One dose (0.5 mL) of MenACWY conjugate vaccine supplied as an extemporaneous mixing just before injection of the lyophilized component (MenA) reconstituted with the liquid component (MenCWY) was administered at 2-, 4-, and 12-months as IM injections in the anterolateral area of the right thigh.
Biological: DTaP-Hib-IPV
IM injections of 3 doses of 0.5 mL each of DTaP-Hib-IPV supplied in prefilled vial were administered at 2-, 3-, and 4-months in the anterolateral area of the left thigh.
Other Name: Combined diphtheria, tetanus toxoid, acellular pertussis, Haemophilus influenzae type B and inactivated polio vaccine; Pediacel
Biological: PCV
IM injections of 3 doses of 0.5 mL each of PCV supplied in pre-filled syringe were administered at 2-, 4-, and 12-months (Groups 2 and 3) or 13-months (Group 1) in the anterolateral area of the left thigh.
Other Name: Heptavalent Streptoccus pneumonia; Prevnar
Biological: MMR
IM injection of one dose of 0.5 mL of MMR obtained by extemporaneous mixing just before injection of powder and the solvent for solution was administered at 13 months in the anterolateral area of the left thigh.
Other Name: Measles, mumps, and rubella vaccine; Priorix
Biological: Hib
IM injection of one dose 0.5 mL of Hib supplied in pre-filled syringe was administered at 13 months in the anterolateral area of the right thigh.
Other Name: Vaxem Hib
Experimental: MenACWY-CRM and Routine Vaccines (Group 3)

Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age.

This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.

Biological: MenACWY-CRM
One dose (0.5 mL) of MenACWY conjugate vaccine supplied as an extemporaneous mixing just before injection of the lyophilized component (MenA) reconstituted with the liquid component (MenCWY) was administered at 2-, 4-, and 12-months as IM injections in the anterolateral area of the right thigh.
Biological: DTaP-Hib-IPV
IM injections of 3 doses of 0.5 mL each of DTaP-Hib-IPV supplied in prefilled vial were administered at 2-, 3-, and 4-months in the anterolateral area of the left thigh.
Other Name: Combined diphtheria, tetanus toxoid, acellular pertussis, Haemophilus influenzae type B and inactivated polio vaccine; Pediacel
Biological: PCV
IM injections of 3 doses of 0.5 mL each of PCV supplied in pre-filled syringe were administered at 2-, 4-, and 12-months (Groups 2 and 3) or 13-months (Group 1) in the anterolateral area of the left thigh.
Other Name: Heptavalent Streptoccus pneumonia; Prevnar
Biological: MMR
IM injection of one dose of 0.5 mL of MMR obtained by extemporaneous mixing just before injection of powder and the solvent for solution was administered at 13 months in the anterolateral area of the left thigh.
Other Name: Measles, mumps, and rubella vaccine; Priorix
Biological: Hib
IM injection of one dose 0.5 mL of Hib supplied in pre-filled syringe was administered at 13 months in the anterolateral area of the right thigh.
Other Name: Vaxem Hib

  Eligibility

Ages Eligible for Study:   56 Days to 83 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects who were eligible to be enrolled in the study:

  • healthy infants aged 2 months (56 - 83 days old, inclusive);
  • available for the visits scheduled in the study;
  • mother available for blood draw at Visit 1;
  • good health as determined by the clinical judgement of the investigator;
  • whose parents gave written informed consent for the infant to be enrolled in the study. The infant's parents must have been willing for the infant to receive the full primary immunization course.

Exclusion Criteria:

Subjects who were not eligible for the study were those:

  • whose parents had not given or were unwilling or unable to give written informed consent to their child's participation in the study
  • with known hypersensitivity to any vaccines contained within the routine immunization schedule
  • with unacceptable concurrent illnesses or conditions - e.g.:

    1. a severe acute or chronic illness; with any present or suspected serious disease such as metabolic, cardiac or autoimmune disease or insulin dependent diabetes or with any other serious disease (e.g., with signs of cardiac or renal failure or severe malnutrition), including progressive neurological disease;
    2. a genetic anomaly, e.g. Down's syndrome;
    3. any immunodeficiency, including use of systemic corticosteroids;
    4. born at less than 36 weeks gestation;
    5. weighing less than 2.5 kg at birth;
    6. previous clinical or bacteriological diagnosis of meningitis, or with a history of household contact or intimate exposure to an individual with culture proven Neisseria meningitidis disease;
    7. known bleeding diathesis, or any condition associated with a prolonged bleeding time;
  • who have received any prohibited prior or concomitant medications - e.g.:

    1. any immunizations within the 30 days prior to enrollment, with the exception of BCG or hepatitis B;
    2. immunoglobulin;
    3. any blood products;
  • participating in any other clinical trial either currently or in the previous month;
  • unable to adhere to the protocol, including plans to move from the area;
  • Other:

Had any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00488683

Locations
United Kingdom
Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine
Headington, Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
Novartis Vaccines
Novartis
Investigators
Study Chair: Novartis Vaccines and Diagnostics Novartis
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT00488683     History of Changes
Other Study ID Numbers: V59P16, 2006-003476-35
Study First Received: June 19, 2007
Results First Received: May 30, 2013
Last Updated: July 24, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Meningococcal disease
Prevention
Vaccination

Additional relevant MeSH terms:
Meningococcal Infections
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on August 27, 2014