Humoral and Cell Mediated Immunity and Safety of MF59C.1-adjuvanted Subunit Influenza Vaccine or a Conventional Subunit Influenza Vaccine in Previously Unvaccinated Healthy Subjects

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01342796
• Collaborator: (none)
• Enrollment: 84
• Locations: 2
• Arms: 2
• Duration (Months): 9.1
• Patients Per Site: 42
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

This study aims to evaluate the immunogenicity, by means of cell mediated immunity (CMI) and hemagglutination inhibition (HI) assay, and also the safety of a MF59C.1-adjuvanted subunit influenza vaccine compared with a conventional subunit vaccine in previously unvaccinated children aged 6 to <36 months.

Condition or Disease	Intervention/Treatment	Phase
Seasonal Influenza; Influenza; Influenza Due to Unspecified Influenza Virus; Human Influenza	Biological: MF59C.1-adjuvanted subunit influenza vaccine; Biological: Sub unit, Inactivated, Influenza vaccine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Phase II, Randomized, Controlled, Observer-Blind, Clinical Study to Evaluate the Humoral and Cell Mediated Immunity and Safety of Two Intramuscular Doses of MF59C.1-adjuvanted Subunit Influenza Vaccine or Conventional Subunit Influenza Vaccine in Previously Unvaccinated Healthy Subjects Aged 6 to <36 Months
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1	Biological: MF59C.1-adjuvanted subunit influenza vaccine; 2 x 0.25 ml doses administered intramuscularly in the deltoid muscle of (preferably) the non dominant arm
Active Comparator: Arm 2	Biological: Sub unit, Inactivated, Influenza vaccine; 2 x 0.25 ml doses administered intramuscularly in the deltoid muscle of (preferably) the non dominant arm

Outcome Measures

Primary Outcome Measures

1. Cell Mediated Immune (CMI) Responses After In-vitro Restimulation Of Peripheral Blood Mononuclear Cells (PBMC) Following Vaccination. [Day 1, Day 50]

   The CMI responses were determined by intracellular staining/Fluorescence-Activated Cell Sorting(ICS/FACS) after in-vitro restimulation of PBMC with vaccine antigens on day 0 and day 50.

2. Number of Subjects Reporting Unsolicited Adverse Events After Receiving Two Doses of aTIV and TIV [Day 1 to Day 50 post vaccination]

   The number of subjects reporting unsolicited AEs between Day 1 and the study termination i.e., Day 50, after receiving two doses of aTIV and TIV. Data are reported based on the Safety Set.

Secondary Outcome Measures

1. Percentage of Subjects Achieving Seroconversion or Significant Increase in HI Titer [Day 50]

   To evaluate the immune responses by seroconversion of aTIV or TIV according to CHMP criteria for seasonal influenza vaccines as determined by hemagglutination inhibition (HI) test on plasma from previously unvaccinated healthy children aged 6 to < 36 months for all three strains. Criteron: The proportion of subjects achieving seroconversion or significant increase in HI titer should be > 40%.

2. Geometric Mean Ratios (GMR) [Day 50/Day 1]

   To evaluate the immune responses by mean geometric increase (GMR) of aTIV or TIV according to CHMP criteria for seasonal influenza vaccines as determined by hemagglutination inhibition (HI) test on plasma from previously unvaccinated healthy children aged 6 to < 36 months for all three strains. Criterion: Mean geometric increase (GMR) should be > 2.5.

3. Percentage of Subjects With HI Titers >1:40 [Day 50]

   To evaluate the immune responses by proportion of subjects with HI titers >1:40 of aTIV or TIV according to CHMP criteria for seasonal influenza vaccines as determined by hemagglutination inhibition (HI) test on plasma from previously unvaccinated healthy children aged 6 to < 36 months for all three strains. Criterion: The proportion of subjects with HI titers >1:40 should be > 70%

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 36 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male and female previously unvaccinated healthy children aged 6 to <36 months.

Exclusion Criteria:

• Any known or suspected impairment of the immune system, any serious disease.

• Any subjects receiving licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.

• Individuals who have had influenza vaccine or documented suspected influenza disease prior to day 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 21: GZA campus Sint Vincentius	Antwerpen		Belgium	2018
2	Site 22: Kinderartsenpraktijk	Hasselt		Belgium	3500

Sponsors and Collaborators

• Novartis Vaccines

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT01342796
• Other Study ID Numbers: V70_34; 2010-023791-63
• First Posted: Apr 27, 2011
• Last Update Posted: Apr 19, 2021
• Last Verified: Feb 1, 2019

• Keywords provided by Novartis Vaccines: Cell mediated immunity; cell mediated immune response; Children; adjuvanted
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from two sites in Belgium.
Pre-assignment Detail	All enrolled subjects were included in the trial.

Arm/Group Title	aTIV Group	TIV Group
Arm/Group Description	Subjects received two doses (0.25mL) of MF59C.1-adjuvanted subunit influenza vaccine administered four weeks apart.	Subjects received two doses (0.25mL) of inactivated, subunit influenza vaccine administered four weeks apart.
Period Title: Overall Study
STARTED	43	41
COMPLETED	40	38
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	aTIV Group	TIV Group	Total
Arm/Group Description	Subjects received two doses (0.25mL) of MF59C.1-adjuvanted subunit influenza vaccine administered four weeks apart.	Subjects received two doses (0.25mL) of inactivated, subunit influenza vaccine administered four weeks apart.	Total of all reporting groups
Overall Participants	43	41	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.2 (8.5)	21.4 (9.7)	20.8 (9.1)
Sex: Female, Male (Count of Participants)
Female	20 46.5%	14 34.1%	34 40.5%
Male	23 53.5%	27 65.9%	50 59.5%

Outcome Measures

1. Primary Outcome

Title	Cell Mediated Immune (CMI) Responses After In-vitro Restimulation Of Peripheral Blood Mononuclear Cells (PBMC) Following Vaccination.
Description	The CMI responses were determined by intracellular staining/Fluorescence-Activated Cell Sorting(ICS/FACS) after in-vitro restimulation of PBMC with vaccine antigens on day 0 and day 50.
Time Frame	Day 1, Day 50

Outcome Measure Data

Analysis Population Description

Per Protocol Set

Arm/Group Title	aTIV Group	TIV Group
Arm/Group Description	Subjects received two doses of MF59C.1-adjuvanted subunit influenza vaccine administered four weeks apart.	Subjects received two doses of inactivated, subunit influenza vaccine administered four weeks apart.
Measure Participants	25	31
Any Cytokine - A/H1N1, Day 1	631	655
Any Cytokine - A/H1N1, Day 50	1560	1137
Any Cytokine - A/H3N2, Day 1	503	462
Any Cytokine - A/H3N2, Day 50	1328	671
Any Cytokine - B/Brisbane, (N=19, 24), Day 1	648	753
Any Cytokine - B/Brisbane, Day 50	2369	1062
Any cytokine - B/Florida, Day 1	605	749
Any cytokine - B/Florida, Day 50	1607	996
Any Cytokine - SEB, Day 1	77048	107200
Any Cytokine - SEB, Day 50	80400	105013
Any cytokine -Tetanus toxoid, Day 1	1246	1368
Any cytokine -Tetanus toxoid, Day 50	1162	1229
IL-2- A/H1N1, Day 1	283	240
IL-2- A/H1N1, Day 50	1141	642
IL-2 - A/H3N2, Day 1	212	184
IL-2 - A/H3N2, Day 50	925	387
IL-2- B/Brisbane, Day 1	301	330
IL-2- B/Brisbane, Day 50	1704	610
IL-2 - B/Florida, Day 1	375	275
IL-2 - B/Florida, Day 50	1094	541
IL-2 - SEB, Day 1	67524	93312
IL-2 - SEB, Day 50	67357	92489
IL-2 - Tetanus toxoid, Day 1	604	672
IL-2 - Tetanus toxoid, Day 50	659	765
IFN-γ - A/H1N1, Day 1	92	116
IFN-γ - A/H1N1, Day 50	257	248
IFN-γ - A/H3N2, Day 1	78	78
IFN-γ - A/H3N2, Day 50	191	130
IFN-γ -B/Brisbane, Day 1	83	122
IFN-γ -B/Brisbane, Day 50	331	106
IFN-γ - B/Florida, Day 1	112	94
IFN-γ - B/Florida, Day 50	193	145
IFN-γ - SEB, Day 1	3615	4780
IFN-γ - SEB, Day 50	3858	4519
IFN-γ - Tetanus toxoid, Day 1	156	148
IFN-γ - Tetanus toxoid, Day 50	74	163
TNF-α- A/H1N1, Day 1	128	133
TNF-α- A/H1N1, Day 50	495	290
TNF-α - A/H3N2, Day 1	81	69
TNF-α - A/H3N2, Day 50	447	202
TNF-α - B/Brisbane, Day 1	116	152
TNF-α - B/Brisbane, Day 50	921	251
TNF-α - B/Florida, Day 1	149	171
TNF-α - B/Florida, Day 50	614	244
TNF-α-SEB, Day 1	25467	37856
TNF-α-SEB, Day 50	32510	34805
TNF-α-Tetanus toxoid, Day 1	537	541
TNF-α-Tetanus toxoid, Day 50	384	644
IL-13 - A/H1N1, Day 1	232	170
IL-13 - A/H1N1, Day 50	242	347
IL-13 - A/H3N2, Day 1	250	174
IL-13 - A/H3N2, Day 50	361	231
IL-13 - B/Brisbane, Day 1	184	168
IL-13 - B/Brisbane, Day 50	346	221
IL-13 - B/Florida, Day 1	150	88
IL-13 - B/Florida, Day 50	97	93
IL-13 -SEB, Day 1	1017	950
IL-13 -SEB, Day 50	772	993
IL-13 -Tetanus toxoid, Day 1	166	222
IL-13 -Tetanus toxoid, Day 50	247	293

2. Primary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events After Receiving Two Doses of aTIV and TIV
Description	The number of subjects reporting unsolicited AEs between Day 1 and the study termination i.e., Day 50, after receiving two doses of aTIV and TIV. Data are reported based on the Safety Set.
Time Frame	Day 1 to Day 50 post vaccination

Outcome Measure Data

Analysis Population Description

All subjects in the Exposed Set (all enrolled subjects who actually received a study vaccine) who provided post-baseline safety data.

Arm/Group Title	aTIV Group	TIV Group
Arm/Group Description	Subjects received two doses of MF59C.1-adjuvanted subunit influenza vaccine administered four weeks apart.	Subjects received two doses of inactivated, subunit influenza vaccine administered four weeks apart.
Measure Participants	43	41
Any Adverse Event (AE)	20 46.5%	18 43.9%
At least possibly related AE	1 2.3%	3 7.3%
Any SAE	0 0%	2 4.9%
At least possibly related SAE	0 0%	0 0%
AE leading to discontinuation	0 0%	0 0%
Death	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Subjects Achieving Seroconversion or Significant Increase in HI Titer
Description	To evaluate the immune responses by seroconversion of aTIV or TIV according to CHMP criteria for seasonal influenza vaccines as determined by hemagglutination inhibition (HI) test on plasma from previously unvaccinated healthy children aged 6 to < 36 months for all three strains. Criteron: The proportion of subjects achieving seroconversion or significant increase in HI titer should be > 40%.
Time Frame	Day 50

Outcome Measure Data

Analysis Population Description

Per Protocol Set

Arm/Group Title	aTIV Group	TIV Group
Arm/Group Description	Subjects received two doses of MF59C.1-adjuvanted subunit influenza vaccine administered four weeks apart.	Subjects received two doses of inactivated, subunit influenza vaccine administered four weeks apart.
Measure Participants	25	30
A/H1N1/California	100 232.6%	73 178%
A/H3N2/Victoria	100 232.6%	93 226.8%
B/Brisbane	100 232.6%	53 129.3%

4. Secondary Outcome

Title	Geometric Mean Ratios (GMR)
Description	To evaluate the immune responses by mean geometric increase (GMR) of aTIV or TIV according to CHMP criteria for seasonal influenza vaccines as determined by hemagglutination inhibition (HI) test on plasma from previously unvaccinated healthy children aged 6 to < 36 months for all three strains. Criterion: Mean geometric increase (GMR) should be > 2.5.
Time Frame	Day 50/Day 1

Outcome Measure Data

Analysis Population Description

Per Protocol Set

Arm/Group Title	aTIV Group	TIV Group
Arm/Group Description	Subjects received two doses of MF59C.1-adjuvanted subunit influenza vaccine administered four weeks apart.	Subjects received two doses of inactivated, subunit influenza vaccine administered four weeks apart.
Measure Participants	25	30
A/H1N1/California	41	9.99
A/H3N2/Victoria	199	35
B/Brisbane	34	5.63

5. Secondary Outcome

Title	Percentage of Subjects With HI Titers >1:40
Description	To evaluate the immune responses by proportion of subjects with HI titers >1:40 of aTIV or TIV according to CHMP criteria for seasonal influenza vaccines as determined by hemagglutination inhibition (HI) test on plasma from previously unvaccinated healthy children aged 6 to < 36 months for all three strains. Criterion: The proportion of subjects with HI titers >1:40 should be > 70%
Time Frame	Day 50

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	aTIV Group	TIV Group
Arm/Group Description	Subjects received two doses of MF59C.1-adjuvanted subunit influenza vaccine administered four weeks apart.	Subjects received two doses of inactivated, subunit influenza vaccine administered four weeks apart.
Measure Participants	25	30
A/H1N1/California	100 232.6%	93 226.8%
A/H3N2/Victoria	100 232.6%	97 236.6%
B/Brisbane	100 232.6%	57 139%

Adverse Events

Time Frame	All solicited AEs and unsolicited AEs were collected from Day 1 to Day 7; all unsolicited SAEs, medically attended AEs, AEs leading to withdrawal from the study were collected from Day 1 to Day 50.
Arm/Group Title	aTIV (6 to <36 Months)		TIV (6 to <36 Months)
Arm/Group Description
All Cause Mortality
	aTIV (6 to <36 Months)		TIV (6 to <36 Months)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	aTIV (6 to <36 Months)		TIV (6 to <36 Months)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		2/41 (4.9%)
Infections and infestations
Varicella	0/43 (0%)		1/41 (2.4%)
Pneumonia	0/43 (0%)		1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	aTIV (6 to <36 Months)		TIV (6 to <36 Months)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/43 (86%)		29/41 (70.7%)
Gastrointestinal disorders
Diarrhoea	11/43 (25.6%)		11/41 (26.8%)
Vomiting	3/43 (7%)		5/41 (12.2%)
General disorders
Crying	6/43 (14%)		7/41 (17.1%)
Injection site erythema	8/43 (18.6%)		2/41 (4.9%)
Injection site haemorrhage	4/43 (9.3%)		1/41 (2.4%)
Injection site induration	3/43 (7%)		3/41 (7.3%)
Injection site pain	11/43 (25.6%)		9/41 (22%)
Pyrexia	19/43 (44.2%)		15/41 (36.6%)
Nasopharyngitis	5/43 (11.6%)		4/41 (9.8%)
Bronchitis	3/43 (7%)		1/41 (2.4%)
Nervous system disorders
Somnolence	11/43 (25.6%)		12/41 (29.3%)
Psychiatric disorders
Eating Disorder	11/43 (25.6%)		11/41 (26.8%)
Irratability	11/43 (25.6%)		7/41 (17.1%)

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.