Trial Outcomes & Findings for A Pilot Study to Assess the Immunogenicity and Reactogenicity of High Versus Standard Dose TIV (NCT NCT02263040)

NCT ID: NCT02263040

Last Updated: 2019-01-28

Results Overview

Seroconversion to influenza strains contained in the vaccine, as measured by hemagglutination inhibition (HAI) assay. 4-fold or greater increase.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 170 participants
• Primary outcome timeframe: 21 days (18-28)
• Results posted on: 2019-01-28

Participant Flow

Participant milestones

Measure	High Dose Fluzone Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5 mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either 2014/15 OR 2015/16	Fluzone (Standard Dose) Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5 mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either: 2014/15 OR 2015/16
Overall Study STARTED	87	83
Overall Study COMPLETED	87	83
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	High Dose Fluzone n=87 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine	Fluzone (Standard Dose) n=83 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine	Total n=170 Participants Total of all reporting groups
Age, Continuous	46 years n=87 Participants	50 years n=83 Participants	47.5 years n=170 Participants
Sex: Female, Male Female	64 Participants n=87 Participants	59 Participants n=83 Participants	123 Participants n=170 Participants
Sex: Female, Male Male	23 Participants n=87 Participants	24 Participants n=83 Participants	47 Participants n=170 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Canada	87 participants n=87 Participants	83 participants n=83 Participants	170 participants n=170 Participants
Underlying chronic medical condition	5 Participants n=87 Participants	4 Participants n=83 Participants	9 Participants n=170 Participants

PRIMARY outcome

Timeframe: 21 days (18-28)

Population: A blood sample from one participant was hemolysed and not available for analysis

Seroconversion to influenza strains contained in the vaccine, as measured by hemagglutination inhibition (HAI) assay. 4-fold or greater increase.

Outcome measures

Measure	High Dose Fluzone n=86 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=83 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Number of Participants With Seroconversion to A/California/07/2009 (H1N1)	41 Participants	21 Participants

PRIMARY outcome

Timeframe: 21 days post vaccination (18-28)

Four-fold or higher rise in titres to A/Texas/50/2012 (H3N2) as measured by hemagglutination inhibition assay

Outcome measures

Measure	High Dose Fluzone n=24 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=22 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Number of Participants With Seroconversion to A/Texas/50/2012 (H3N2)	17 Participants	4 Participants

PRIMARY outcome

Timeframe: 21 days post-vaccination (18-28)

Four fold or higher increase in titres to B/Phuket/3073/2013 as measured by hemagglutination inhibition assay

Outcome measures

Measure	High Dose Fluzone n=62 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=61 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Number of Participants With Seroconversion to Influenza B/Phuket/3073/2013	29 Participants	12 Participants

PRIMARY outcome

Timeframe: 21 days post vaccination (18-28)

Four-fold or higher rise in titres against A/Switzerland/9715293/2013 (H3N2) as measured by hemagglutination inhibition assay

Outcome measures

Measure	High Dose Fluzone n=62 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=61 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Number of Participants With Seroconversion to A/Switzerland/9715293/2013 (H3N2)	58 Participants	49 Participants

PRIMARY outcome

Timeframe: 21 days post-vaccination (18-28)

Four fold or higher increase in titres to B/Massachusetts/02/2012 as measured by hemagglutination inhibition assay

Outcome measures

Measure	High Dose Fluzone n=24 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=22 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Number of Participants With Seroconversion to B/Massachusetts/02/2012	8 Participants	3 Participants

SECONDARY outcome

Timeframe: 21 days (18-28)

GMFR (mean fold increase) time2/time1, as measured by hemagglutination inhibition assay

Outcome measures

Measure	High Dose Fluzone n=86 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=83 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Geometric Mean Fold Ratio (GMFR) Against A/California/07/2009 (H1N1)	1.38 fold ratio Interval 1.28 to 1.48	1.20 fold ratio Interval 1.13 to 1.27

SECONDARY outcome

Timeframe: 21 days (18-28)

GMFR (mean fold increase) time2/time1, as measured by HAI titres

Outcome measures

Measure	High Dose Fluzone n=62 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=61 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Geometric Mean Fold Ratio (GMFR): A/Switzerland/9715293/2013	1.82 fold ratio Interval 1.7 to 1.94	1.67 fold ratio Interval 1.53 to 1.81

SECONDARY outcome

Timeframe: 21 days (18-28)

GMFR (mean fold increase) time2/time1, as measured by HAI titres

Outcome measures

Measure	High Dose Fluzone n=24 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=22 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Geometric Mean Fold Ratio (GMFR): A/Texas/50/2012	1.76 fold ratio Interval 1.36 to 2.16	1.15 fold ratio Interval 1.08 to 1.22

SECONDARY outcome

Timeframe: 21 days (18-28)

GMFR (mean fold increase) time2/time1, as measured by HAI titres

Outcome measures

Measure	High Dose Fluzone n=62 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=61 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Geometric Mean Fold Ratio (GMFR): B/Phuket/3073/2013 Ether-treated	1.32 fold ratio Interval 1.23 to 1.41	1.19 fold ratio Interval 1.11 to 1.27

SECONDARY outcome

Timeframe: 21 days (18-28)

GMFR (mean fold increase) time2/time1, as measured by HAI titres

Outcome measures

Measure	High Dose Fluzone n=24 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=22 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Geometric Mean Fold Ratio (GMFR): B/Massachusetts/02/2012 Ether-treated	1.20 fold ratio Interval 1.11 to 1.29	1.08 fold ratio Interval 1.02 to 1.14

SECONDARY outcome

Timeframe: 7 days

Population: All participants were able to provide data

Any local adverse event following immunization,self reported in daily diary Includes the maximum values for any one of: redness, warmth, swelling, or bruising

Outcome measures

Measure	High Dose Fluzone n=87 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=83 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Number of Participants Reporting Adverse Event: Injection Site none	47 Participants	62 Participants
Number of Participants Reporting Adverse Event: Injection Site mild	34 Participants	21 Participants
Number of Participants Reporting Adverse Event: Injection Site moderate	6 Participants	0 Participants

SECONDARY outcome

Timeframe: 7 days

Any systemic adverse event following immunization,self reported in daily diary Includes the maximum value reported for any one of: myalgia, arthralgia, headache, malaise, fatigue, weakness, sweating, shivering, or feverishness

Defined as:

None: Not at all Mild: Present, but did not interfere with activities Moderate: Interfered with activities, but didn't prevent them Extreme: Prevented activities

Outcome measures

Measure	High Dose Fluzone n=87 Participants Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=83 Participants Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
Number of Participants Reporting Adverse Event: Systemic None	41 Participants	42 Participants
Number of Participants Reporting Adverse Event: Systemic Mild	23 Participants	25 Participants
Number of Participants Reporting Adverse Event: Systemic Moderate	18 Participants	13 Participants
Number of Participants Reporting Adverse Event: Systemic Extreme	5 Participants	3 Participants

Adverse Events

High Dose Fluzone

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Fluzone (Standard Dose)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	High Dose Fluzone n=87 participants at risk Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain Fluzone High-Dose: Influenza vaccine Either season: 2014/15 OR 2015/16	Fluzone (Standard Dose) n=83 participants at risk Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults Fluzone (standard dose): Influenza vaccine Either season: 2014/15 OR 2015/16
General disorders Myalgia	14.9% 13/87 • Number of events 13 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination	7.2% 6/83 • Number of events 6 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination
General disorders Headache	9.2% 8/87 • Number of events 8 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination	4.8% 4/83 • Number of events 4 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination
General disorders Fatigue	10.3% 9/87 • Number of events 9 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination	7.2% 6/83 • Number of events 6 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination
General disorders Malaise	5.7% 5/87 • Number of events 5 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination	4.8% 4/83 • Number of events 4 • 6 months Daily diary for 7 days Nursing note at day 21 Asked to report to clinic for 6 months after vaccination

Additional Information

Dr. Allison McGeer

Mount Sinai Hospital, Toronto

Phone: 416-586-3118

Email: allison.mcgeer@sinaihealthsystem.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place