Study to Assess the Immune Response and the Safety Profile of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Taiwanese Adults 65 Years of Age and Older

• ClinicalTrials.gov Identifier: NCT04537234
• Recruitment Status: Completed
• First Posted: September 3, 2020
• Results First Posted: November 8, 2021
• Last Update Posted: April 7, 2022
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Influenza (Healthy Volunteers)
• Interventions: Biological: High-Dose Quadrivalent Influenza Vaccine; Biological: Standard-Dose Quadrivalent Influenza Vaccine
• Enrollment: 165

Participant Flow

Recruitment Details	The study was conducted at 4 active centers in Taiwan. A total of 165 participants were enrolled and randomized between 10 November 2020 to 12 January 2021.
Pre-assignment Details	A total of 165 participants were vaccinated in the study.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description	Participants received a single injection of 0.7 milliliters (mL) QIV-HD, intramuscularly (IM) at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Period Title: Overall Study
Started	82	83
Completed	80	83
Not Completed	2	0
Reason Not Completed
Withdrawal by Subject	2	0

Baseline Characteristics

Arm/Group Title		Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)	Total
Arm/Group Description		Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.	Total of all reporting groups
Overall Number of Baseline Participants		82	83	165
Baseline Analysis Population Description		Analysis was performed on all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	82 participants	83 participants	165 participants
		71.5 (5.37)	71.4 (5.71)	71.4 (5.52)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants	83 participants	165 participants
	Female	47 57.3%	46 55.4%	93 56.4%
	Male	35 42.7%	37 44.6%	72 43.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants	83 participants	165 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	82 100.0%	83 100.0%	165 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0
Description	GMTs of anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria Lineage), and B2 (B Yamagata Lineage). Titers were expressed in terms of 1/dilution.
Time Frame	Day 0 (pre-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the full analysis set (FAS) that included randomized participants who received one of the study vaccine and had a post-vaccination blood sample. Participants were analyzed according to the vaccine group to which they were randomized.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	80	83
Geometric Mean (95% Confidence Interval); Unit of Measure: titers
A/H1N1	23.6; (18.1 to 30.6)	24.1; (18.5 to 31.5)
A/H3N2	111; (78.4 to 156)	169; (120 to 238)
B1	88.0; (66.7 to 116)	98.2; (76.6 to 126)
B2	149; (111 to 199)	160; (121 to 211)

2. Primary Outcome

Title	Geometric Mean Titers of Influenza Vaccine Antibodies at Day 28
Description	GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). Titers were expressed in terms of 1/dilution.
Time Frame	Day 28 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	80	83
Geometric Mean (95% Confidence Interval); Unit of Measure: titers
A/H1N1	283; (221 to 364)	109; (78.2 to 151)
A/H3N2	643; (522 to 791)	427; (324 to 563)
B1	812; (645 to 1023)	324; (253 to 414)
B2	707; (595 to 840)	361; (290 to 450)

3. Primary Outcome

Title	Geometric Mean Titers Ratio (GMTR) of Influenza Vaccine Antibodies
Description	GMTRs of anti-influenza antibodies were measured by using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). GMTRs were calculated as the ratio of GMTs post-vaccination (on Day 28) and pre-vaccination (on Day 0).
Time Frame	Day 0 (pre-vaccination), Day 28 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	80	83
Geometric Mean (95% Confidence Interval); Unit of Measure: ratio
A/H1N1	12.0; (9.09 to 15.9)	4.50; (3.47 to 5.82)
A/H3N2	5.81; (4.28 to 7.87)	2.53; (1.87 to 3.41)
B1	9.23; (7.00 to 12.2)	3.30; (2.48 to 4.39)
B2	4.76; (3.65 to 6.21)	2.26; (1.76 to 2.89)

4. Primary Outcome

Title	Percentage of Participants Achieving Seroconversion Against Influenza Virus Antigens
Description	Anti-influenza antibodies were measured by HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). Seroconversion was defined as either a pre-vaccination HAI titer less than (<) 10 (1/dilution) at Day 0 and a post-vaccination titer greater than or equal to (>=) 40 (1/dilution) at Day 28 or a pre-vaccination titer >=10 (1/dilution) at Day 0 and a >= four-fold increase in post-vaccination titer at Day 28.
Time Frame	Day 28 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	80	83
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1	86.3; (76.7 to 92.9)	50.6; (39.4 to 61.8)
A/H3N2	61.3; (49.7 to 71.9)	28.9; (19.5 to 39.9)
B1	78.8; (68.2 to 87.1)	37.3; (27.0 to 48.7)
B2	50.0; (38.6 to 61.4)	24.1; (15.4 to 34.7)

5. Primary Outcome

Title	Percentage of Participants With Antibody Titers >=40 (1/Dilution) at Day 0
Description	Antibody titer was measured by using HAI assay method for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage).
Time Frame	Day 0 (pre-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	80	83
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1	33.8; (23.6 to 45.2)	36.1; (25.9 to 47.4)
A/H3N2	76.3; (65.4 to 85.1)	84.3; (74.7 to 91.4)
B1	81.3; (71.0 to 89.1)	85.5; (76.1 to 92.3)
B2	85.0; (75.3 to 92.0)	86.7; (77.5 to 93.2)

6. Primary Outcome

Title	Percentage of Participants With Antibody Titers >=40 (1/Dilution) at Day 28
Description	Antibody titer was measured using HAI assay method for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage).
Time Frame	Day 28 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	80	83
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1	97.5; (91.3 to 99.7)	79.5; (69.2 to 87.6)
A/H3N2	100; (95.5 to 100)	96.4; (89.8 to 99.2)
B1	98.8; (93.2 to 100)	98.8; (93.5 to 100)
B2	100; (95.5 to 100)	100; (95.7 to 100)

7. Primary Outcome

Title	Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)
Description	An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not had any causal relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB.
Time Frame	Within 30 minutes post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the safety analysis set (SafAS) that included participants who had received one of the study vaccines and had any safety data available; and were analyzed according to the vaccine they actually received.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	82	83
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

8. Primary Outcome

Title	Number of Participants With Solicited Injection Site and Systemic Reactions
Description	A solicited reaction was an "expected" adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRB and considered as related to the product administered. Solicited injection site reactions included pain, erythema, swelling, induration, and bruising. Solicited systemic reactions included fever, headache, malaise, myalgia and shivering.
Time Frame	Within 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title		Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:		Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed		82	83
Measure Type: Count of Participants; Unit of Measure: Participants
Injection site Pain	Number Analyzed	82 participants	83 participants
		37 45.1%	30 36.1%
Injection site Erythema	Number Analyzed	82 participants	83 participants
		8 9.8%	7 8.4%
Injection site Swelling	Number Analyzed	82 participants	83 participants
		8 9.8%	2 2.4%
Injection site Induration	Number Analyzed	82 participants	83 participants
		8 9.8%	2 2.4%
Injection site Bruising	Number Analyzed	82 participants	83 participants
		0 0.0%	0 0.0%
Fever	Number Analyzed	80 participants	83 participants
		1 1.3%	0 0.0%
Headache	Number Analyzed	82 participants	83 participants
		9 11.0%	4 4.8%
Malaise	Number Analyzed	82 participants	83 participants
		9 11.0%	7 8.4%
Myalgia	Number Analyzed	82 participants	83 participants
		22 26.8%	10 12.0%
Shivering	Number Analyzed	82 participants	83 participants
		3 3.7%	3 3.6%

9. Primary Outcome

Title	Number of Participants With Unsolicited Adverse Events
Description	An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not had any causal relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination.
Time Frame	Within 28 days post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	82	83
Measure Type: Count of Participants; Unit of Measure: Participants
	8 9.8%	12 14.5%

10. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) Including Adverse Event of Special Interest (AESIs)
Description	An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. AESIs was defined as event for which ongoing monitoring and rapid communication by the investigator to the sponsor was done.
Time Frame	From Day 0 up to 28 days post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS.

Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description:	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Overall Number of Participants Analyzed	82	83
Measure Type: Count of Participants; Unit of Measure: Participants
SAE	0 0.0%	0 0.0%
AESIs	0 0.0%	0 0.0%

Adverse Events

Time Frame	Unsolicited AEs were collected from Day 0 (post-vaccination) up to 28 days post-vaccination. Solicited reaction data were collected up to Day 7 post-vaccination. SAE data were collected from Day 0 (post-vaccination) up to 28 days post-vaccination.
Adverse Event Reporting Description	A solicited reaction was an "expected" adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRB and considered as related to the product administered. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the CRB in terms of diagnosis and/or onset window post-vaccination. Analysis was performed on SafAS.
Arm/Group Title	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
Arm/Group Description	Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.		Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
All-Cause Mortality
	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/82 (0.00%)		0/83 (0.00%)
Serious Adverse Events
	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0.00%)		0/83 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Group 1: High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		Group 2: Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/82 (56.10%)		35/83 (42.17%)
General disorders
Injection Site Erythema † 1	8/82 (9.76%)	8	7/83 (8.43%)	7
Injection Site Induration † 1	8/82 (9.76%)	8	2/83 (2.41%)	2
Injection Site Pain † 1	37/82 (45.12%)	37	30/83 (36.14%)	30
Injection Site Swelling † 1	8/82 (9.76%)	8	2/83 (2.41%)	2
Malaise † 1	9/82 (10.98%)	9	7/83 (8.43%)	7
Musculoskeletal and connective tissue disorders
Myalgia † 1	22/82 (26.83%)	22	10/83 (12.05%)	10
Nervous system disorders
Headache † 1 [1]	9/82 (10.98%)	9	5/83 (6.02%)	5
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment; [1] Headache events that occurred after 7 days post-vaccination were considered as unsolicited AE.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable participant matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi Pasteur
• Phone: 800-633-1610 ext 6#
• EMail: Contact-US@sanofi.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chen JY, Hsieh SM, Hwang SJ, Liu CS, Li X, Fournier M, Yeh TY, Yin JK, Samson SI. Immunogenicity and safety of high-dose quadrivalent influenza vaccine in older adults in Taiwan: A phase III, randomized, multi-center study. Vaccine. 2022 Oct 26;40(45):6450-6454. doi: 10.1016/j.vaccine.2022.09.078. Epub 2022 Oct 7.

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT04537234
• Other Study ID Numbers: QHD00023; U1111-1238-1970 ( Other Identifier: UTN )
• First Submitted: August 26, 2020
• First Posted: September 3, 2020
• Results First Submitted: October 8, 2021
• Results First Posted: November 8, 2021
• Last Update Posted: April 7, 2022