Safety of Two Trivalent Influenza Vaccines Evaluated in Children and Adolescents 4 to 17 Years of Age

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01857206
• Collaborator: (none)
• Enrollment: 2,055
• Locations: 34
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 60.4
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

Evaluate safety and tolerability of TIVa or TIVb vaccine in healthy children and adolescents 4 to 17 years of age.

Condition or Disease	Intervention/Treatment	Phase
Influenza; Fever	Biological: Mammalian cell based flu vaccine; Biological: Egg based flu vaccine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2055 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Phase III, Observer Blind, Randomized, Controlled, Multicenter Study to Evaluate the Safety of a Trivalent Subunit Influenza Vaccine Produced Either in Mammalian Cell Culture or in Embryonated Chicken Eggs (Fluvirin®), in Healthy Children and Adolescents 4 to 17 Years of Age.
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TIVc Subjects ≥4 to ≤17 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Biological: Mammalian cell based flu vaccine
Active Comparator: TIVf Subjects ≥4 to ≤17 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.	Biological: Egg based flu vaccine

Outcome Measures

Primary Outcome Measures

1. Number Of Subjects Reporting Solicited Local and Systemic Adverse Events and Other Indicators Of Reactogenicity After Any Vaccination. [Day 1 to Day 7 after any vaccination]

   Safety was assessed as the number of subjects who reported solicited local and systemic adverse events and other indicators of reactogenicity following two doses of either mammalian cell culture-derived or egg-derived trivalent influenza vaccination in subjects aged ≥4 To ≤17 Years.

2. Number Of Subjects Reporting Unsolicited Adverse Events After Any Vaccination. [Day 1 to Day49 for subjects aged ≥4 To ≤8 years not previously vaccinated. Day 1 to Day 38 for subjects aged ≥4 To ≤8 years previously vaccinated and all subjects aged ≥9 To ≤17 years.]

   Safety was assessed as the number of subjects who reported unsolicited adverse events following vaccination with either mammalian cell culture-derived or egg-derived trivalent influenza vaccination in subjects aged ≥4 To ≤17 Years.

3. Number Of Subjects Reporting Unsolicited Serious Adverse Events After Any Vaccination. [Day 1 to Day 183 for previously vaccinated subjects and Day 213 for not-previously vaccinated subjects]

   Safety was assessed as the number of subjects who reported serious adverse events (SAEs), medically attended AEs and new onset of chronic diseases (NOCD) in subjects aged ≥4 To ≤17 Years.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy subjects 4-17 years of age

Exclusion Criteria:

• Subjects who are not healthy,

• Subjects who are pregnant or breast feeding,

• Subjects with a history of severe allergic reaction or allergic to any of the vaccine components.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	320, Novartis Investigational Site	Mobile	Alabama	United States	36608
2	312, Novartis Investigational Site	Ponte Vedra	Florida	United States	32081
3	313, Novartis Investigational Site	Augusta	Kansas	United States	67010
4	305, Novartis Investigational Site	Newton	Kansas	United States	67114
5	302, Novartis Investigational Site	Wichita	Kansas	United States	67205
6	301, Novartis Investigational Site	Wichita	Kansas	United States	67207
7	311, Novartis Investigational Site	Fremont	Nebraska	United States	68025
8	308, Novartis Investigational Site	Winston-salem	North Carolina	United States	27103
9	317, Novartis Investigational Site	Cleveland	Ohio	United States	44121
10	309, Novartis Investigational Site	Tulsa	Oklahoma	United States	74127
11	314, Novartis Investigational Site	Warwick	Rhode Island	United States	02886
12	319, Novartis Investigational Site	Mount Pleasant	South Carolina	United States	29464
13	310, Novartis Investigational Site	Bristol	Tennessee	United States	37620
14	318, Novartis Investigational Site	Nashville	Tennessee	United States	37203
15	304, Novartis Investigational Site	Salt Lake City	Utah	United States	84109
16	306, Novartis Investigational Site	Salt Lake City	Utah	United States	84121
17	315, Novartis Investigational Site	Salt Lake	Utah	United States	84124
18	303, Novartis Investigational Site	South Jordan	Utah	United States	84095
19	100, Novartis Investigational Site	Westmead	New South Wales	Australia	2145
20	108, Novartis Investigational Site	Auchenflower	Queensland	Australia	4066
21	107, Novartis Investigational Site	Sherwood	Queensland	Australia	4075
22	104, Novartis Investigational Site	North Adelaide	South Australia	Australia	5006
23	103, Novartis Investigational Site	Carlton	Victoria	Australia	3010
24	105, Novartis Investigational Site	Subiaco	Western Australia	Australia	6008
25	151, Novartis Investigational Site	Takapuna	Auckland	New Zealand	0622
26	150, Novartis Investigational Site	Beckenham	Christchurch	New Zealand	8024
27	250, Novartis Investigational Site	Muntinlupa City	Alabang	Philippines	1781
28	251, Novartis Investigational Site	Muntinlupa City	Alabang	Philippines	1781
29	254, Novartis Investigational Site	Muntinlupa City	Alabang	Philippines	1781
30	253, Novartis Investigational Site	Manila	Ermita	Philippines	1001
31	252, Novartis Investigation Site	Manila	Sampaloc	Philippines	1001
32	201, Novartis Investigational Site	Khon Kaen	Muang	Thailand	40002
33	200, Novartis Investigational Site	Bangkok	Rajathevi	Thailand	10400
34	202, Novartis Investigational Site	Bangkoknoi	Siriraj	Thailand	10700

Sponsors and Collaborators

• Novartis Vaccines

Investigators

• Study Chair: Novartis Vaccines and Diagnostics, Novartis Vaccines

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT01857206
• Other Study ID Numbers: V58_31; U1111-1139-9440
• First Posted: May 20, 2013
• Last Update Posted: Dec 5, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Novartis Vaccines: Influenza; children and adolescents; trivalent vaccine; cell culture; embryonated chicken eggs
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at a total of 34 centers in 5 countries: 18 sites in the US, 6 sites in Australia, 2 sites in New Zealand, 5 sites in the Philippines and 3 sites in Thailand.

Arm/Group Title	TIVc	TIVf
Arm/Group Description	Subjects ≥4 to ≤17 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥4 to ≤17 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.
Period Title: Overall Study
STARTED	1372	683
COMPLETED	1359	673
NOT COMPLETED	13	10

Baseline Characteristics

Arm/Group Title	TIVc	TIVf	TOTAL
Arm/Group Description	Subjects ≥4 to ≤17 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥4 to ≤17 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.	Total of all reporting groups
Overall Participants	1372	683	2055
Age (year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [year]	9.1 (3.8)	9.3 (3.9)	9.1 (3.8)
Sex: Female, Male (Count of Participants)
Female	703 51.2%	349 51.1%	1052 51.2%
Male	669 48.8%	334 48.9%	1003 48.8%

Outcome Measures

1. Primary Outcome

Title	Number Of Subjects Reporting Solicited Local and Systemic Adverse Events and Other Indicators Of Reactogenicity After Any Vaccination.
Description	Safety was assessed as the number of subjects who reported solicited local and systemic adverse events and other indicators of reactogenicity following two doses of either mammalian cell culture-derived or egg-derived trivalent influenza vaccination in subjects aged ≥4 To ≤17 Years.
Time Frame	Day 1 to Day 7 after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was done on the solicited safety dataset, i.e. the subjects in the exposed population who provided postvaccination solicited safety data.

Arm/Group Title	TIVc (≥4 to ≤8 Years)	TIVf (≥4 to ≤8 Years)	TIVc (≥9 to ≤17 Years)	TIVf (≥9 to ≤17 Years)
Arm/Group Description	Subjects ≥4 to ≤8 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥4 to ≤8 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥9 to ≤17 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥9 to ≤17 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.
Measure Participants	688	341	682	341
Any Local	422	202	370	160
Injection site Induration (AE)	109	43	46	33
Injection site Swelling (AE)	87	37	36	26
Injection site Erythema (AE)	148	57	72	37
Injection site Ecchymosis (AE)	68	30	27	11
Injection site Pain (AE)	384	186	356	142
Any Systemic	252	110	267	113
Chills (AE)	47	17	39	7
Nausea (AE)	57	26	45	16
Myalgia (AE)	113	41	126	44
Arthralgia (AE)	39	16	54	14
Headache (AE)	105	42	128	57
Fatigue (AE)	92	34	109	56
Loss of appetite (AE)	68	25	50	12
Malaise (AE)	112	43	99	46
Sweating (AE)	39	20	52	23
Body Temperature (≥38°C) (AE)	48	30	12	5
≥40°C (Other Indicator)	3	0	0	0
Prevention of pain and/or fever (Other Indicator)	61	29	24	10
Treatment of pain and/or fever (Other Indicator)	90	40	39	18

2. Primary Outcome

Title	Number Of Subjects Reporting Unsolicited Adverse Events After Any Vaccination.
Description	Safety was assessed as the number of subjects who reported unsolicited adverse events following vaccination with either mammalian cell culture-derived or egg-derived trivalent influenza vaccination in subjects aged ≥4 To ≤17 Years.
Time Frame	Day 1 to Day49 for subjects aged ≥4 To ≤8 years not previously vaccinated. Day 1 to Day 38 for subjects aged ≥4 To ≤8 years previously vaccinated and all subjects aged ≥9 To ≤17 years.

Outcome Measure Data

Analysis Population Description

Analysis was done on the unsolicited safety dataset, i.e. the subjects in the exposed population who provided postvaccination unsolicited safety data.

Arm/Group Title	TIVc (≥4 to ≤8 Years)	TIVf (≥4 to ≤8 Years)	TIVc (≥9 to ≤17 Years)	TIVf (≥9 to ≤17 Years)
Arm/Group Description	Subjects ≥4 to ≤8 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥4 to ≤8 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥9 to ≤17 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥9 to ≤17 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.
Measure Participants	688	340	681	341
Any AE	277	139	158	88
At least possibly related AE	50	26	32	22

3. Primary Outcome

Title	Number Of Subjects Reporting Unsolicited Serious Adverse Events After Any Vaccination.
Description	Safety was assessed as the number of subjects who reported serious adverse events (SAEs), medically attended AEs and new onset of chronic diseases (NOCD) in subjects aged ≥4 To ≤17 Years.
Time Frame	Day 1 to Day 183 for previously vaccinated subjects and Day 213 for not-previously vaccinated subjects

Outcome Measure Data

Analysis Population Description

Analysis was done on the unsolicited safety dataset, i.e. the subjects in the exposed population who provided postvaccination unsolicited safety data.

Arm/Group Title	TIVc (≥4 to ≤8 Years)	TIVf (≥4 to ≤8 Years)	TIVc (≥9 to ≤17 Years)	TIVf (≥9 to ≤17 Years)
Arm/Group Description	Subjects ≥4 to ≤8 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥4 to ≤8 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥9 to ≤17 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.	Subjects ≥9 to ≤17 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.
Measure Participants	688	340	681	341
SAE	17	7	7	9
At least possibly related SAE	0	0	0	0
AE leading to withdrawal	0	0	0	0
Medically attended AE	284	139	172	105
NOCD	5	4	3	1
Death	0	0	0	0

Adverse Events

Time Frame	6 months for subjects aged ≥4 to ≤8 years previously vaccinated and all subjects aged ≥9 to ≤17 Years 7 months for subjects aged ≥4 to ≤8 years not previously vaccinated.
Adverse Event Reporting Description	For subjects aged ≥4 to ≤8 years not previously vaccinated AEs collected from day 1 to 7 and day 29 to 35. SAEs, medically attended AEs and NOCD till day 213 For subjects aged ≥4 to ≤8 years previously vaccinated and subjects aged ≥9 to ≤17 Years AEs were collected from day 1 to 7. SAEs, medically attended AEs and NOCD were collected till day 183
Arm/Group Title	TIVc(4-8Years )		TIVf(4-8Years )		TIVc(9-17Years )		TIVf(9-17Years )
Arm/Group Description	Subjects ≥4 to ≤8 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.		Subjects ≥4 to ≤8 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.		Subjects ≥9 to ≤17 years of age received one or two doses of mammalian cell-culture-derived trivalent influenza vaccine based on their previous vaccination status.		Subjects ≥9 to ≤17 years of age received one or two doses of egg-derived trivalent influenza vaccine based on their previous vaccination status.
All Cause Mortality
	TIVc(4-8Years )		TIVf(4-8Years )		TIVc(9-17Years )		TIVf(9-17Years )
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	TIVc(4-8Years )		TIVf(4-8Years )		TIVc(9-17Years )		TIVf(9-17Years )
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/688 (2.5%)		7/341 (2.1%)		7/682 (1%)		9/341 (2.6%)
Blood and lymphatic system disorders
LYMPHADENITIS	0/688 (0%)		0/341 (0%)		1/682 (0.1%)		0/341 (0%)
Hepatobiliary disorders
CHOLECYSTITIS	0/688 (0%)		0/341 (0%)		1/682 (0.1%)		0/341 (0%)
Infections and infestations
ACUTE SINUSITIS	2/688 (0.3%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
APPENDICITIS PERFORATED	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
BRONCHITIS	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
CELLULITIS	1/688 (0.1%)		1/341 (0.3%)		0/682 (0%)		0/341 (0%)
DENGUE FEVER	2/688 (0.3%)		0/341 (0%)		1/682 (0.1%)		3/341 (0.9%)
GASTROENTERITIS	2/688 (0.3%)		0/341 (0%)		0/682 (0%)		1/341 (0.3%)
NASOPHARYNGITIS	0/688 (0%)		1/341 (0.3%)		0/682 (0%)		0/341 (0%)
PHARYNGITIS	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
PHARYNGOTONSILLITIS	0/688 (0%)		1/341 (0.3%)		0/682 (0%)		0/341 (0%)
PNEUMONIA	0/688 (0%)		0/341 (0%)		1/682 (0.1%)		0/341 (0%)
RESPIRATORY SYNCYTIAL VIRUS INFECTION	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
SINUSITIS BACTERIAL	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
URINARY TRACT INFECTION	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
WOUND INFECTION	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
Injury, poisoning and procedural complications
ANIMAL BITE	3/688 (0.4%)		3/341 (0.9%)		0/682 (0%)		0/341 (0%)
ANIMAL SCRATCH	0/688 (0%)		1/341 (0.3%)		1/682 (0.1%)		0/341 (0%)
HEAD INJURY	0/688 (0%)		0/341 (0%)		1/682 (0.1%)		0/341 (0%)
INJURY	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
LIGAMENT RUPTURE	0/688 (0%)		0/341 (0%)		0/682 (0%)		1/341 (0.3%)
MULTIPLE INJURIES	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
RADIUS FRACTURE	0/688 (0%)		0/341 (0%)		1/682 (0.1%)		1/341 (0.3%)
Nervous system disorders
CEREBELLAR ATAXIA	1/688 (0.1%)		0/341 (0%)		0/682 (0%)		0/341 (0%)
VISUAL FIELD DEFECT	0/688 (0%)		0/341 (0%)		0/682 (0%)		1/341 (0.3%)
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS	0/688 (0%)		0/341 (0%)		0/682 (0%)		1/341 (0.3%)
Reproductive system and breast disorders
ADNEXAL TORSION	0/688 (0%)		0/341 (0%)		0/682 (0%)		1/341 (0.3%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	0/688 (0%)		1/341 (0.3%)		0/682 (0%)		0/341 (0%)
Other (Not Including Serious) Adverse Events
	TIVc(4-8Years )		TIVf(4-8Years )		TIVc(9-17Years )		TIVf(9-17Years )
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	545/688 (79.2%)		267/341 (78.3%)		489/682 (71.7%)		220/341 (64.5%)
Gastrointestinal disorders
NAUSEA	61/688 (8.9%)		27/341 (7.9%)		45/682 (6.6%)		17/341 (5%)
General disorders
CHILLS	48/688 (7%)		18/341 (5.3%)		39/682 (5.7%)		8/341 (2.3%)
FATIGUE	95/688 (13.8%)		36/341 (10.6%)		109/682 (16%)		56/341 (16.4%)
INJECTION SITE ERYTHEMA	164/688 (23.8%)		68/341 (19.9%)		85/682 (12.5%)		43/341 (12.6%)
INJECTION SITE HAEMORRHAGE	69/688 (10%)		30/341 (8.8%)		27/682 (4%)		11/341 (3.2%)
INJECTION SITE INDURATION	114/688 (16.6%)		45/341 (13.2%)		48/682 (7%)		33/341 (9.7%)
INJECTION SITE PAIN	433/688 (62.9%)		211/341 (61.9%)		385/682 (56.5%)		159/341 (46.6%)
INJECTION SITE SWELLING	95/688 (13.8%)		43/341 (12.6%)		41/682 (6%)		29/341 (8.5%)
MALAISE	112/688 (16.3%)		43/341 (12.6%)		99/682 (14.5%)		46/341 (13.5%)
PYREXIA	63/688 (9.2%)		42/341 (12.3%)		17/682 (2.5%)		9/341 (2.6%)
Infections and infestations
NASOPHARYNGITIS	36/688 (5.2%)		17/341 (5%)		21/682 (3.1%)		15/341 (4.4%)
UPPER RESPIRATORY TRACT INFECTION	133/688 (19.3%)		60/341 (17.6%)		58/682 (8.5%)		26/341 (7.6%)
VIRAL INFECTION	35/688 (5.1%)		14/341 (4.1%)		14/682 (2.1%)		8/341 (2.3%)
Metabolism and nutrition disorders
DECREASED APPETITE	68/688 (9.9%)		25/341 (7.3%)		51/682 (7.5%)		12/341 (3.5%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	41/688 (6%)		16/341 (4.7%)		57/682 (8.4%)		15/341 (4.4%)
MYALGIA	115/688 (16.7%)		41/341 (12%)		130/682 (19.1%)		45/341 (13.2%)
Nervous system disorders
HEADACHE	108/688 (15.7%)		44/341 (12.9%)		137/682 (20.1%)		62/341 (18.2%)
Skin and subcutaneous tissue disorders
HYPERHIDROSIS	39/688 (5.7%)		20/341 (5.9%)		52/682 (7.6%)		23/341 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.