Clinical trial NCT00488683: B Cell Response to a Primary and a Booster Course of the Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Meningococcal Disease
Keywords: Meningococcal disease
Prevention
Vaccination
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2007-06-20
Enrollment: 216
Sex: ALL
Minimum age (years): 56
Maximum age (years): 83
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility 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.

Primary outcomes:
measure: Summary of Memory B Cells Per 2 x 105 LOC by Serogroup A, C, W-135 and Y
timeFrame: 1 month after primary vaccination and immediately before third dose at 12 months of age
Secondary outcomes:
measure: Memory B Cells by Serogroup A, C, W-135 and Y
timeFrame: 1 month after primary vaccination and immediately before third dose
measure: 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
timeFrame: 1 month after primary vaccination and 1 month after third vaccination
measure: Memory B Cells 1 Month After Primary Vaccination and Rise From Pre-third Dose to 1 Month After Third Dose of MenACWY-CRM Vaccination
timeFrame: 1 month after primary and pre-third and 1 month after third vaccination
measure: Memory B Cells 1 Month After Primary Vaccination and 1 Week After Third Vaccination by Serogroup A, C, W-135 and Y
timeFrame: One month after primary vaccination and 1 week after third vaccination
measure: CRM197 Specific Memory B Cells 1 Month After Primary Vaccination and at 12 Months of Age and One Month After MenACWY-CRM Third Vaccination
timeFrame: 5 months (B cells), 12 months and 13 months (B cells and IgG) of age
measure: 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
timeFrame: Before and one month after booster vaccination
measure: 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
timeFrame: Before and one month after booster vaccination
measure: 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
timeFrame: One month after primary vaccination
measure: Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination
timeFrame: Day 0, 7, 14, 49, 90, and 120 after MenACWY-CRM vaccination at month 4
measure: Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination
timeFrame: Day 0, 7, 14, 30, 49, 90,120 after MenACWY-CRM vaccination at month 4
measure: 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
timeFrame: Day 1 (IgG) and one month after primary vaccination (B cells)
measure: 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
timeFrame: 1 month post primary vaccination (B cells) and 12 months (hSBA titers and IgG)
measure: 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
timeFrame: 1 month post primary vaccination (B cells) and 12 months (hSBA titers and IgG)
measure: Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations.
timeFrame: 7 days post each MenACWY-CRM and routine infant vaccination
measure: Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations
timeFrame: 7 days post vaccination at 2, 3, and 4 months of age
measure: Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age
timeFrame: 7 days post 12 month vaccination
measure: Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age
timeFrame: 7 days post 12 months vaccination
measure: 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
timeFrame: Before and one month after booster vaccination
measure: Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination
timeFrame: Day 0, 7, 14, 30, 49, 90,120 after MenACWY-CRM vaccination at month 4
Other outcomes:
Locations:
city: Headington
country: United Kingdom
facility: Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine
state: Oxford
Study officials:
affiliation: Novartis
name: Novartis Vaccines and Diagnostics
role: STUDY_CHAIR
References:
citation: Blanchard-Rohner G, Snape MD, Kelly DF, O'Connor D, John T, Clutterbuck EA, Ohene-Kena B, Klinger CL, Odrljin T, Pollard AJ. The B-cell response to a primary and booster course of MenACWY-CRM(1)(9)(7) vaccine administered at 2, 4 and 12 months of age. Vaccine. 2013 May 7;31(20):2441-8. doi: 10.1016/j.vaccine.2013.03.036. Epub 2013 Apr 6.