Immunogenicity and Safety of Meningococcal ACWY Conjugate Vaccine in Healthy Subjects From 2 to 18 Years in Taiwan

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01410474
• Collaborator: Novartis Vaccines (Industry)
• Enrollment: 341
• Locations: 3
• Arm: 1
• Duration (Months): 5
• Patients Per Site: 113.7
• Patients Per Site Per Month: 22.6

Study Details

Study Description

Brief Summary

This study will evaluate the immunogenicity and safety of a single injection of Novartis Meningococcal ACWY conjugate vaccine in healthy subjects from 2 to 18 years in Taiwan.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Meningitis	Biological: Meningococcal ACWY conjugate vaccine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 341 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Multicenter, Open-label Study to Evaluate Immunogenicity and Safety of Novartis Meningococcal ACWY Conjugate Vaccine (MenACWY-CRM) in Healthy Subjects From 2 to 18 Years in Taiwan
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2-18 years	Biological: Meningococcal ACWY conjugate vaccine; All subjects received a single dose of Meningococcal ACWY conjugate vaccine and had blood draw at day 1 and day 29.

Outcome Measures

Primary Outcome Measures

1. Percentage of Overall Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination [Day 1 and Day 29]

   Immunogenicity was measured as the percentage of subjects with hSBA seroresponse and associated 95% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y, evaluated by serum bactericidal assay using human complement (hSBA), at 28 days after one vaccination of MenACWY-CRM (day 29). Seroresponse is defined as: for subjects with a prevaccination hSBA titer <1:4, a postvaccination hSBA titer ≥1:8. for subjects with a prevaccination hSBA titer ≥1:4, an increase in hSBA titer of at least four times the prevaccination titer.

Secondary Outcome Measures

1. Percentage of Subjects With Seroresponse, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination, by Age Group [Day 1 and Day 29]

   Immunogenicity was measured as the percentage of subjects with hSBA response and associated 95% CI, directed against N. meningitidis serogroups A, C, W and Y, at Day 29, by age groups. Seroresponse is defined as: for subjects with a prevaccination hSBA titer <1:4, a postvaccination hSBA titer ≥1:8. for subjects with a prevaccination hSBA titer ≥1:4, an increase in hSBA titer of at least four times the prevaccination titer.

2. Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination [Day 1 and 29]

   Immunogenicity was measured as hSBA GMTs and associated 95% CI, against N. meningitidis serogroups A, C, W and Y, before the vaccination (Day 1) and 28 days after MenACWY-CRM vaccination (Day 29), by age group and overall.

3. Geometric Mean Ratios (GMRs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination [Day 1 and Day 29]

   Immunogenicity was measured as ratio of postvaccination GMTs to prevaccination GMTs and associated 95% CI, against N. meningitidis serogroups A, C, W and Y, at 28 days after MenACWY-CRM vaccination (Day 29), by age group and overall.

4. Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination [Day 1 and 29]

   Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI, before vaccination (Day 1) and 28 days after MenACWY-CRM vaccination (Day 29), bye age group and overall.

5. Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After MenACWY-CRM Vaccination, Age 2 to 5 Years [From day 1 through day 7 postvaccination]

   Safety was assessed as the number of subjects aged 2 to 5 years who reported solicited local and systemic adverse events (AEs) within days 1 through 7 after MenACWY-CRM vaccination.

6. Number of Subjects Who Reported Solicited Local and Systemic AEs After MenACWY-CRM Vaccination, Age 6 to 18 Years [From day 1 through day 7 postvaccination]

   Safety was assessed as the number of subjects aged 6 to 18 years who reported solicited local and systemic AEs within days 1 through 7 after MenACWY-CRM vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Healthy subjects from 2 up to and including 18 years of age

2. Who are in good health as determined by : medical history, physical exam,clinical judgment of the investigator, who have a negative urine pregnancy test for female subjects ≥11 years of age

Exclusion Criteria:

Individuals not eligible to be enrolled in the study were those:

1. Who had a previous confirmed or suspected disease caused by N. meningitidis.

2. Who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrolment.

3. Who have previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) (licensed or investigational).

4. Who have received any vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 30 days from the study vaccines.

5. Who have experienced within the 7 days prior to enrolment significant acute infection or have experienced fever within 3 days prior to enrolment.

6. Who have any serious acute, chronic or progressive who have epilepsy or any progressive neurological disease or history of Guillain-Barre syndrome.

7. Who have a history of any anaphylaxis, serious vaccine reactions, or allergy to any vaccine components.

8. Who have a known or suspected impairment/alteration of immune function, either congenital or acquired

9. Who are known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

10. Who have Down's syndrome or other known cytogenic disorders.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mackay Memorial Hospital,	Taipei	Taiwan	China	10002
2	National Taiwan University Hospital	Taipei	Taiwan	China	10002
3	Far Eastern Memorial Hospital,	Taipei	Taiwan	China	22060

Sponsors and Collaborators

• Novartis
• Novartis Vaccines

Investigators

• Principal Investigator: Li Min Huang, Dr., Dr. Li Min Huang, National Taiwan University Hospital
• Principal Investigator: Nan Chang Chiu, Dr., Mackay Memorial Hospital
• Principal Investigator: Shu Jen Yeh, Dr., Far Eastern Memorial Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT01410474
• Other Study ID Numbers: V59_49
• First Posted: Aug 5, 2011
• Last Update Posted: Sep 22, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Novartis: Meningococcal; ACWY; bacterial meningitis; conjugate vaccine; healthy; children; adolescents; Taiwan
• Additional relevant MeSH terms: Meningitis, Bacterial; Meningitis

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at three study centres in Taiwan.
Pre-assignment Detail	All enrolled subjects were included in the trial.

Arm/Group Title	2-10 Years	11-18 Years
Arm/Group Description	Subjects 2-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.
Period Title: Overall Study
STARTED	173	168
COMPLETED	173	167
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	2-10 Years	11-18 Years	Total
Arm/Group Description	Subjects 2-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Total of all reporting groups
Overall Participants	173	168	341
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	6.3 (2.6)	14.0 (2.2)	10.1 (4.5)
Sex: Female, Male (Count of Participants)
Female	92 53.2%	88 52.4%	180 52.8%
Male	81 46.8%	80 47.6%	161 47.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Overall Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination
Description	Immunogenicity was measured as the percentage of subjects with hSBA seroresponse and associated 95% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y, evaluated by serum bactericidal assay using human complement (hSBA), at 28 days after one vaccination of MenACWY-CRM (day 29). Seroresponse is defined as: for subjects with a prevaccination hSBA titer <1:4, a postvaccination hSBA titer ≥1:8. for subjects with a prevaccination hSBA titer ≥1:4, an increase in hSBA titer of at least four times the prevaccination titer.
Time Frame	Day 1 and Day 29

Outcome Measure Data

Analysis Population Description

Analysis was done on modified intention-to-treat (MITT) population i.e subjects in the exposed population who provided evaluable serum samples whose assay results were available for at least one serogroup on day 1 and/or day 29.

Arm/Group Title	Overall (2 to 18 Years)
Arm/Group Description	Subjects 2 to 18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.
Measure Participants	336
MenA (N=335)	83
MenC (N=333)	93
MenW (N=334)	50
MenY (N=333)	65

2. Secondary Outcome

Title	Percentage of Subjects With Seroresponse, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination, by Age Group
Description	Immunogenicity was measured as the percentage of subjects with hSBA response and associated 95% CI, directed against N. meningitidis serogroups A, C, W and Y, at Day 29, by age groups. Seroresponse is defined as: for subjects with a prevaccination hSBA titer <1:4, a postvaccination hSBA titer ≥1:8. for subjects with a prevaccination hSBA titer ≥1:4, an increase in hSBA titer of at least four times the prevaccination titer.
Time Frame	Day 1 and Day 29

Outcome Measure Data

Analysis Population Description

Analysis was done on MITT population

Arm/Group Title	2-10 Years	11-18 Years
Arm/Group Description	Subjects 2-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.
Measure Participants	170	166
Men A (N=170,165)	77	89
MenC (N=167,166)	92	95
MenW (N=168,166)	54	46
MenY (N=167,166)	61	69

3. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination
Description	Immunogenicity was measured as hSBA GMTs and associated 95% CI, against N. meningitidis serogroups A, C, W and Y, before the vaccination (Day 1) and 28 days after MenACWY-CRM vaccination (Day 29), by age group and overall.
Time Frame	Day 1 and 29

Outcome Measure Data

Analysis Population Description

Analysis was done on MITT population

Arm/Group Title	2-10 Years	11-18 Years	Overall (2 to 18 Years)
Arm/Group Description	Subjects 2-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 2 to 18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.
Measure Participants	170	166	336
MenA at Day 1(N=170,165,335)	2.05	2.2	2.12
MenA at Day 29(N=170,165,335)	32	88	53
MenC at Day 1 (N=167,166,333)	2.66	3.64	3.11
MenC at Day 29 (N=167,166,333)	117	273	179
MenW at Day 1 (N=168,166,334)	7.32	15	10
MenW at Day 29 (N=168,166,334)	49	104	71
MenY at Day 1 (N=167,166,333)	3.21	3.95	3.56
MenY at Day 29 (N=167,166,333)	26	56	38

4. Secondary Outcome

Title	Geometric Mean Ratios (GMRs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination
Description	Immunogenicity was measured as ratio of postvaccination GMTs to prevaccination GMTs and associated 95% CI, against N. meningitidis serogroups A, C, W and Y, at 28 days after MenACWY-CRM vaccination (Day 29), by age group and overall.
Time Frame	Day 1 and Day 29

Outcome Measure Data

Analysis Population Description

Analysis was done on MITT population

Arm/Group Title	2-10 Years	11-18 Years	Overall (2 to 18 Years)
Arm/Group Description	Subjects 2-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 2 to 18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.
Measure Participants	170	166	336
MenA(N=170,165,335)	16	40	25
MenC (N=167,166,333)	44	75	57
MenW (N=168,166,334)	6.66	6.91	6.78
MenY (N=167,166,333)	8.02	14	11

5. Secondary Outcome

Title	Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination
Description	Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI, before vaccination (Day 1) and 28 days after MenACWY-CRM vaccination (Day 29), bye age group and overall.
Time Frame	Day 1 and 29

Outcome Measure Data

Analysis Population Description

Analysis was done on MITT population

Arm/Group Title	2-10 Years	11-18 Years	Overall (2 to 18 Years)
Arm/Group Description	Subjects 2-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.	Subjects 2 to 18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.
Measure Participants	170	166	336
MenA at Day 1 (N=170,165,335)	1	4	3
MenA at Day 29 (N=170,165,335)	77	90	83
MenC at Day 1 (N=167,166,333)	11	23	17
MenC at Day 29 (N=167,166,333)	95	98	96
MenW at Day 1 (N=168,166,334)	47	70	58
MenW at Day 29 (N=168,166,334)	93	99	96
MenY at Day 1 (N=167,166,333)	22	26	24
MenY at Day 29 (N=167,166,333)	78	86	82

6. Secondary Outcome

Title	Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After MenACWY-CRM Vaccination, Age 2 to 5 Years
Description	Safety was assessed as the number of subjects aged 2 to 5 years who reported solicited local and systemic adverse events (AEs) within days 1 through 7 after MenACWY-CRM vaccination.
Time Frame	From day 1 through day 7 postvaccination

Outcome Measure Data

Analysis Population Description

Analysis was done on safety population i.e. the subjects in the exposed population who provided post-baseline safety data.

Arm/Group Title	2-5 Years
Arm/Group Description	Subjects 2-5 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1
Measure Participants	72
Injection site tenderness	27
Injection site erythema	7
Injection site induration	6
Change in eating habits	2
Sleepiness	3
Irritability	5
Vomiting	7
Diarrhea	2
Rash - Any	4
Rash - Urticarial	1
Fever (≥38°C)	4

7. Secondary Outcome

Title	Number of Subjects Who Reported Solicited Local and Systemic AEs After MenACWY-CRM Vaccination, Age 6 to 18 Years
Description	Safety was assessed as the number of subjects aged 6 to 18 years who reported solicited local and systemic AEs within days 1 through 7 after MenACWY-CRM vaccination.
Time Frame	From day 1 through day 7 postvaccination

Outcome Measure Data

Analysis Population Description

Analysis was done on safety population.

Arm/Group Title	6-10 Years	11-18 Years	Overall (6-18 Years)
Arm/Group Description	Subjects 6-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1	Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1	Subjects 6-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1
Measure Participants	101	167	268
Injection site pain	37	62	99
Injection site erythema	17	17	34
Injection site induration	14	12	26
Chills	2	6	8
Nausea	10	10	20
Malaise	13	35	48
Myalgia	20	49	69
Arthralgia	3	13	16
Headache	11	29	40
Rash - Any	7	4	11
Rash - Urticarial	3	3	6
Fever (≥38°C)	3	2	5

Adverse Events

Time Frame	Throughout the study period (from day 1 through day 29)
Adverse Event Reporting Description	A systematic adverse event is equivalent to an event that was solicited by the diary card, whereas a non-systematic event is equivalent to an event that was not solicited by the diary card.
Arm/Group Title	2-10 Years		11-18 Years		Overall (2 to 18 Years)
Arm/Group Description	Subjects 2-10 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.		Subjects 11-18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.		Subjects 2 to 18 years of age received one 0.5 mL dose of MenACWY-CRM vaccination as intramuscular (IM) injection at Day 1.
All Cause Mortality
	2-10 Years		11-18 Years		Overall (2 to 18 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	2-10 Years		11-18 Years		Overall (2 to 18 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/173 (0.6%)		0/167 (0%)		1/340 (0.3%)
Infections and infestations
Pneumonia	1/173 (0.6%)	1	0/167 (0%)	0	1/340 (0.3%)	1
Other (Not Including Serious) Adverse Events
	2-10 Years		11-18 Years		Overall (2 to 18 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/173 (63.6%)		98/167 (58.7%)		208/340 (61.2%)
Gastrointestinal disorders
Nausea	10/173 (5.8%)	10	10/167 (6%)	10	20/340 (5.9%)	20
General disorders
Injection site erythema	58/173 (33.5%)	58	43/167 (25.7%)	43	101/340 (29.7%)	101
Injection site induration	49/173 (28.3%)	49	36/167 (21.6%)	36	85/340 (25%)	85
Injection site pain	64/173 (37%)	64	62/167 (37.1%)	62	126/340 (37.1%)	126
Malaise	13/173 (7.5%)	13	35/167 (21%)	35	48/340 (14.1%)	48
Infections and infestations
Nasopharyngitis	10/173 (5.8%)	10	2/167 (1.2%)	2	12/340 (3.5%)	12
Upper respiratory tract infection	16/173 (9.2%)	16	6/167 (3.6%)	6	22/340 (6.5%)	22
Musculoskeletal and connective tissue disorders
Arthralgia	3/173 (1.7%)	3	13/167 (7.8%)	13	16/340 (4.7%)	16
Myalgia	20/173 (11.6%)	20	49/167 (29.3%)	49	69/340 (20.3%)	69
Nervous system disorders
Headache	13/173 (7.5%)	13	29/167 (17.4%)	29	42/340 (12.4%)	42
Skin and subcutaneous tissue disorders
Rash	11/173 (6.4%)	11	4/167 (2.4%)	4	15/340 (4.4%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.