Evaluation of Antibody Persistence Following 4 MenACWY Vaccinations

• MenACWY (Biological): Four Intramuscular doses of MenACWY vaccine at 2, 4, 6 and 12 months of age followed by two blood samples at 13 and 24 months of age.

Primary outcomes

• Number of Subjects With Any Solicited Adverse Events (AEs) Within 30 Minutes After Each Vaccination. [Within 30 minutes of each vaccination]: Solicited signs and symptoms occurring within 30 minutes following each vaccination, include solicited local events (e.g. injection site erythema, induration and tenderness -threshold for Erythema and Induration: Type II- None \[<10mm\], Any\[>=10 mm\]), solicited systemic events (e.g. change in eating habits, sleepiness, irritability, vomiting, diarrhea, fever\[ body temperature >=38°C measured preferably via tympanic route\]), and any other solicited event like use of analgesic/antipyretics for treatment or for prophylaxis
• Number of Subjects With Any Solicited Local AEs From Day 1 to Day 7 After Each Vaccination [From Day 1 to Day 7 after each vaccination]: Solicited local AEs reported from day 1 to day 7 after each vaccination were assessed. Assessed local symptoms include injection site erythema, injection site induration and injection site tenderness. Any = incidence of a particular symptom regardless of intensity grade.Threshold for Erythema and Induration: Type II None (<10 mm), Any (>=10 mm)
• Number of Subjects With Any Solicited Systemic AEs From Day 1 to Day 7 After Each Vaccination. [From Day 1 to Day 7 after each vaccination]: Solicited systemic AEs reported from day 1 to day 7 after each vaccination were assessed. Assessed systemic symptoms include change in eating habits, sleepiness, irritability, vomiting, diarrhea and fever (body temperature ≥ 38°C (100.4°F)).
• Number of Subjects With Any Medically Attended Unsolicited AEs and AEs Leading to Premature Withdrawal [From Day 1 to Visit 6 (at 24 Months of age)]: An unsolicited adverse event is an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject parent(s)/legal guardian(s)\] who has signed the informed consent. All medically attended unsolicited AEs were collected from Day 1 to Visit 6.
• Number of Subjects With Serious AEs (SAEs) [From Day 1 to Visit 6 (At 24 months of age)]: Subjects reporting SAEs from day 1 to visit 6 (at 24 months of age) were assessed. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in one or more of the following: death, is life-threatening, required or prolonged hospitalization, persistent or significant disability/incapacity, congenital anomaly/or birth defect, An important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above.
• Percentage of Subjects With Human Serum Bactericidal Assay (hSBA) Titers ≥ 8 Against Each N.Meningitidis Serogroup A,C,W and Y at 24 Months of Age. [At 24 months of age (Visit 6)]: To assess antibody persistence against N. meningitidis serogroups A, C, W and Y at 1 year after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine as measured by serum bactericidal assay using human serum complement.
• Percentage of Subjects With Rabbit Serum Bactericidal Assay (rSBA) Titers ≥ 8, Against Each N.Meningitidis Serogroup at 24 Months of Age [At 24 months of age (Visit 6)]: To assess antibody persistence against N. Meningitidis serogroups A, C, W and Y at 1 year after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine as measured by serum bactericidal assay using rabbit serum complement
• Percentage of Subjects With Rabbit Serum Bactericidal Assay (rSBA) Titers ≥ 128 Against Each N.Meningitidis Serogroup at 24 Months of Age [At 24 months of age (Visit 6)]: To assess antibody persistence against N. Meningitidis serogroups A, C, W and Y at 1 year after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine as measured by serum bactericidal assay using rabbit serum complement

Secondary outcomes

• Percentage of Subjects With hSBA ≥8 Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age [At 13 months of age (Visit 5)]: To assess antibody response against N. meningitidis serogroups A, C, W and Y at 1 month after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine as measured by serum bactericidal assay using human serum complement.
• Percentage of Subjects With rSBA Titers ≥ 8 Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age [At 13 months of age (Visit 5)]: To assess antibody response against N. meningitidis serogroups A, C, W and Y at 1 month after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine as measured by serum bactericidal assay using rabbit serum complement.
• Percentage of Subjects With rSBA Titers ≥ 128 Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age [At 13 months of age (Visit 5)]: To assess antibody response against N. meningitidis serogroups A, C, W and Y at 1 month after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine as measured by serum bactericidal assay using rabbit serum complement.
• hSBA Geometric Mean Titers (GMTs) Against Each N. Meningitidis Serogroups A, C, W and Y at 24 Months of Age [At 24 months of age (Visit 6)]: To assess persistence of antibody response in terms of GMTs using hSBA assay against N. meningitidis serogroups A, C, W and Y at 1 year after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine.
• rSBA GMTs Against Each N. Meningitidis Serogroups A, C, W and Y at 24 Months of Age [At 24 months of age (Visit 6)]: To assess persistence of antibody response in terms of GMTs using rSBA assay against N. meningitidis serogroups A, C, W and Y at 1 year after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine.
• hSBA GMTs Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age [At 13 months of age (Visit 5)]: To assess antibody response in terms of GMTs using hSBA assay against N. meningitidis serogroups A, C, W and Y at 1 month after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine.
• rSBA GMTs Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age. [At 13 months of age (Visit 5)]: To assess antibody response in terms of GMTs using rSBA assay against N. meningitidis serogroups A, C, W and Y at 1 month after completion of a 4-dose infant vaccination series (2, 4, 6 and 12 months of age) of MenACWY vaccine.

Sex: All, ages: 2 Months to 24 Months, accepts healthy volunteers

Inclusion Criteria:

1. Healthy male and female 2 month-old infants (55 - 89 days) on the day of consent.
2. Infants whose parents or legal guardians have voluntary given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Infants whose parents or legal guardians can comply with study procedures including follow-up

Exclusion Criteria:

1. Previously received any meningococcal A, C, W and Y vaccines.
2. Previous confirmed or suspected disease caused by N. meningitidis or who have had household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection at any time since birth.
3. Progressive, unstable or uncontrolled clinical conditions.
4. A history of anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component, such as latex allergy.
5. Experienced significant acute or chronic infection within the previous 7 days or have experienced fever (temperature ≥ 38.0°C \[100.4°F\]) within the previous 3 days.
6. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
7. Received treatment with systemic administration corticosteroids (PO/IV/IM) for more than 14 consecutive days from birth
8. Ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation (including Hepatitis B immune globulin) at any time since birth and for the full length of the study.
9. Any bleeding disorder which is considered as a contraindication to intramuscular injection or blood draw.
10. Any condition which, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
11. Received or are planning to receive any investigational or non-registered medicinal product from birth and throughout the study.
12. Received oral or parenteral antibiotic treatment in the 3 days prior to the scheduled blood draw (topical antibiotics are acceptable, including antibiotic eye drops).
13. Relatives of site research staff working on this study.

Participant flow

Outcome results

• Number of Subjects With Any Solicited Adverse Events (AEs) Within 30 Minutes After Each Vaccination. (Primary), Count of participants, Participants: MenACWY Group 0
• Number of Subjects With Any Solicited Local AEs From Day 1 to Day 7 After Each Vaccination (Primary), Count of participants, Participants: MenACWY Group 4
• Number of Subjects With Any Solicited Systemic AEs From Day 1 to Day 7 After Each Vaccination. (Primary), Count of participants, Participants: MenACWY Group 29
• Number of Subjects With Any Medically Attended Unsolicited AEs and AEs Leading to Premature Withdrawal (Primary), Count of participants, Participants: MenACWY Group 85
• Number of Subjects With Serious AEs (SAEs) (Primary), Count of participants, Participants: MenACWY Group 26
• Percentage of Subjects With Human Serum Bactericidal Assay (hSBA) Titers ≥ 8 Against Each N.Meningitidis Serogroup A,C,W and Y at 24 Months of Age. (Primary), Number, Percentage of subjects: MenACWY Group 39 (30.4 to 49.1)
• Percentage of Subjects With Rabbit Serum Bactericidal Assay (rSBA) Titers ≥ 8, Against Each N.Meningitidis Serogroup at 24 Months of Age (Primary), Number, Percentage of subjects: MenACWY Group 99 (94.9 to 99.98)
• Percentage of Subjects With Rabbit Serum Bactericidal Assay (rSBA) Titers ≥ 128 Against Each N.Meningitidis Serogroup at 24 Months of Age (Primary), Number, Percentage of subjects: MenACWY Group 98 (93.5 to 99.77)
• Percentage of Subjects With hSBA ≥8 Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age (Secondary), Number, Percentage of subjects: MenACWY Group 94 (88.5 to 97.7)
• Percentage of Subjects With rSBA Titers ≥ 8 Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age (Secondary), Number, Percentage of subjects: MenACWY Group 100 (96.8 to 100.0)
• Percentage of Subjects With rSBA Titers ≥ 128 Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age (Secondary), Number, Percentage of subjects: MenACWY Group 100 (96.8 to 100.0)
• hSBA Geometric Mean Titers (GMTs) Against Each N. Meningitidis Serogroups A, C, W and Y at 24 Months of Age (Secondary), Geometric mean, Titers: MenACWY Group 6.80 (5.19 to 8.93)
• rSBA GMTs Against Each N. Meningitidis Serogroups A, C, W and Y at 24 Months of Age (Secondary), Geometric mean, Titers: MenACWY Group 2269.48 (1761.12 to 2924.59)
• hSBA GMTs Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age (Secondary), Geometric mean, Titers: MenACWY Group 107.90 (85.73 to 135.81)
• rSBA GMTs Against Each N. Meningitidis Serogroups A, C, W and Y at 13 Months of Age. (Secondary), Geometric mean, Titers: MenACWY Group 7394.18 (6057.42 to 9025.93)

Adverse events

Time frame: Solicited local and systemic adverse events (AEs): from Day 1 to Day 7 after each vaccination. Unsolicited AEs, serious AEs (SAEs): From Day 1 to study end (visit 6).

Serious adverse events by term

Other adverse events by term

16 more terms not shown.

• Study Protocol (PDF, 2015-08-25)
• Statistical Analysis Plan (PDF, 2016-06-07)

• GSK Clinical Trials, Study director, GlaxoSmithKline

NIH grants: 2014