FLUCELVAX QUADRIVALENT 

(ccIIV4) a Phase III 

Randomized Controlled Trial

Immunogenicity & Safety Results 

in Young Children

(6 through 47 months of age)

Gregg C. Sylvester, MD, MPH

Chief Medical Officer

Seqirus, Inc.

June 24, 2021
2 |

• Background

• Study Objectives

-Immunogenicity

- Safety

• Study Design

• Inclusion & Exclusion Criteria 

• Demographics 

• Results

• Summary 

AGENDA
3 |

• Flucelvax® Quadrivalent is the only cell-based quadrivalent 

influenza vaccine (ccIIV4) in the United States

• A cell based influenza vaccine avoids egg adaptation, thus 

potentially resulting in a closer match to the FDA-selected strains 

for each season1,2

• Flucelvax Quadrivalent is approved for use in persons 2 years of 

age and older in the United States 

1. Centers for Disease Control and Prevention. https://www.cdc.gov/flu/prevent/cell-based.htm (accessed March 15, 2021) 

2. Rajaram S. et al. Ther Adv Vaccines Immunother. 2020 Feb 22: 8:2515135520908121 

BACKGROUND
4 |

STUDY OBJECTIVES (ccIIV4) IN CHILDREN 6 - 47 MONTHS 

Immunogenicity Objectives (8 endpoints measured)

• Geometric Mean Titer (GMT) ratio (IIV4/ccIIV4)/Vaccine 

Strain (4 endpoints)

• Upper Bound of the 2 sided 95% Confidence Interval 

≤1.5

• Seroconversion Rates (SCR) difference (IIV4-ccIIV4)/Vaccine 

Strain (4 endpoints)

• Upper Bound of the 2 sided 95% CI does not exceed 10 

percentage points

Safety Objectives

• Safety and Tolerability
5 |

• Phase 3 Randomized Controlled Trial

• ccIIV4 (Flucelvax Quadrivalent) versus a US-licensed IIV4 (Afluria 

Quadrivalent)

• 2019–2020 Northern Hemisphere Flu Season

• 47 centers in the United States

•Immunogenicity assessed using hemagglutination inhibition assays for 

A/H1N1, B/Yamagata, and B/Victoria strains and microneutralization 

assay for A/H3N2 strain

• Participants randomized 2:1 (ccIIV4:IIV4)

EudraCT number 2020-002785-13; NCT04074928.

QIV, US-licensed quadrivalent influenza vaccine; QIVc, cell-based quadrivalent influenza vaccine

STUDY DESIGN
6 |

STUDY GROUP

NOT PREVIOUSLY VACCINATED 

†ccIIV4 administed as a 0.5 mL dose; ‡

IIV4 (Afluria®) administered as a 0.25 mL dose for children 6–35 months of age and a 0.5 mL dose for 

children 36–47 months of age.

AE, adverse event; NOCD, new onset of chronic disease; SAE, serious adverse event

IIV4, egg-based quadrivalent influenza vaccine; ccIIV4, cell-based quadrivalent influenza vaccine

Treatment period Follow-up period

Blood sampling

Immunogenicity

Safety follow-up

Vaccination

Rando

mize

d

2:1

ccIIV4†

N=787

IIV4 ‡

N=375

1 29 57 // 209

Solicited 

AEs

Any AEs AEs leading to withdrawal, NOCD, SAEs, medically 

attended AEs, concomitant medications

DAYS

Solicited 

AEs
7 |

STUDY DESIGN

PREVIOUSLY VACCINATED 

†ccIIV4 administed as a 0.5 mL dose; ‡

IIV4 (Afluria®) administered as a 0.25 mL dose for children 6–35 months of age and a 0.5 mL dose for 

children 36–47 months of age.

AE, adverse event; NOCD, new onset of chronic disease; SAE, serious adverse event 

IIV4, egg-based quadrivalent influenza vaccine; ccIIV4, cell-based quadrivalent influenza vaccine

Treatment period Follow-up period

Blood sampling

Immunogenicity

Safety follow-up

Vaccination

Rando

mize

d

2:1

ccIIV4†

N=810

IIV4‡

N=430

1 29 // 181

Solicited 

AEs

Any AEs AEs leading to withdrawal, NOCD, SAEs, medically attended AEs, 

concomitant medications

DAYS
8 |

KEY INCLUSION AND EXCLUSION CRITERIA

†By the parent/legal guardian 

• Healthy children ≥6 

to ≤47 months old

• Ability to comply 

with study 

procedures

• Informed consent/

assent provided†

• Fever

• History of Hypersensitivity to any of the vaccine components

• History of Guillain–Barré syndrome/demyelinating diseases

• History of immunodeficiency or impaired immune function

• Received an influenza vaccination or documented influenza in 

the 6 months prior to informed consent

• Received blood products or immunoglobulins within 180 days 

prior to informed consent

• Received an investigational medical product within 30 days prior 

to informed consent

Inclusion

Exclusion
9 |

ccIIV4

N=1597 (%)

IIV4

N=805 (%)

Total

N=2402 (%)

Age (months) Mean (SD) 28.1 (11.5) 28.2 (11.6) 28.1 (11.7)

Age group 6 months thru 23 months 595 (37.3) 299 (37.1) 894 (37.2)

24 months thru 47 months 1002 (62.7) 506 (62.9) 1508 (62.8)

Sex Male 803 (50.3) 406 (50.4) 1209 (50.3)

Female 794 (49.7) 399 (49.6) 1193 (49.7)

Race* White 1039 (65.1) 539 (67.0) 1578 (65.7)

Black or African American 455 (28.5) 209 (26.0) 664 (27.6)

Ethnicity Hispanic or Latino 434 (27.2) 226 (28.1) 660 (27.5)

Not Hispanic or Latino 1160 (72.6) 575 (71.4) 1735 (72.2)

Vaccination 

History

Not Previously Vaccinated 787 (49.3) 375 (46.6) 1162 (48.4)

Previously Vaccinated 810 (50.7) 430 (53.4) 1240 (51.6)

DEMOGRAPHICS AND BASELINE CHARACTERISTICS

Abbreviations: IIV4 = quadrivalent influenza vaccine; ccIIV4 = cell-based quadrivalent subunit influenza virus vaccine; SD = standard deviation; US = United States

*Other groups represented at 1% or less: Asian, Native Hawaiian or Other Pacific Islander, American Indian or Alaska Native; Race Group “Other” was 4.3%
10 |

IMMUNOGENICITY RESULTS:

GEOMETRIC MEAN TITER RATIOS

†The pre-specified success criterion was that the upper bound of the 2-sided 95% CI for GMT ratios did not exceed 1.5; 

‡Using MN assay. CI, confidence interval; GMT, geometric mean titer; HAI, hemagglutination inhibition assay; MN, microneutralization assay; 

PPS, per-protocol set; IIV4, egg-based quadrivalent influenza vaccine; ccIIV4, cell-based quadrivalent influenza vaccine

GMT GMT ratio 

ccIIV4

(95% CI)

IIV4

(95% CI)

IIV4/ccIIV4

(95% CI)

A/H1N1 78.0 (70.8, 86.0) 57.3 (50.8, 64.6) 0.73 (0.65, 0.84)

A/H3N2‡ 23.1 (21.2, 25.1) 23.9 (21.6, 26.6) 1.04 (0.93, 1.16)

B/Yamagata 35.6 (32.9, 38.6) 26.0 (23.5, 28.6) 0.73 (0.66, 0.81)

B/Victoria 22.4 (20.7, 24.2) 19.6 (17.8, 21.6) 0.88 (0.79, 0.97)

Noninferiority criteria were met for all four strains

0.5

0.7

0.9

1.1

1.3

1.5

1.7

Pre-specified success criterion†

GMT ratio(IIV4/ccIIV4)

A/H1N1 A/H3N2 B/Yamagata B/Victoria

Using cell-based target viruses

Vaccine strain
11 |

IMMUNOGENICITY RESULTS:

SEROCONVERSION RATE DIFFERENCE

†The pre-specified success criterion was that the upper bound of the 2-sided 95% CI for SCR differences did not exceed 10%; 

‡Using MN assay 

CI, confidence interval; HAI, hemagglutination inhibition assay; MN, microneutralization assay; PPS, per-protocol set; IIV4, egg-based 

quadrivalent influenza vaccine; ccIIV4, cell-based quadrivalent influenza vaccine; SCR, seroconversion rate.

SCR SCR difference

ccIIV4

% (95% CI)

IIV4

% (95% CI)

IIV4−ccIIV4

% (95% CI)

A/H1N1 58.2 (55.3, 61.2) 46.8 (42.6, 51.0) −11.46 (−16.44, −6.42)

A/H3N2‡ 27.6 (25.0, 30.4) 30.8 (27.0, 34.7) 3.13 (−1.44, 7.81)

B/Yamagata 46.5 (43.5, 49.5) 31.7 (27.9, 35.6) −14.87 (−19.61, −9.98)

B/Victoria 30.3 (27.6, 33.1) 24.4 (20.9, 28.1) −5.96 (−10.33, −1.44)

Noninferiority criteria were met for all four strains

Pre-specified success criterion†

Difference in SCR %(IIV4−ccIIV4)

A/H1N1 A/H3N2 B/Yamagata B/Victoria

Using cell-based target viruses

Vaccine strain

−2

−4

−6

−8

−10

−20

−12

−14

−16

−18

−22

12

10

8

6

4

2

0
12 |

SAFETY AND TOLERABILITY SUMMARY

SOLICITED LOCAL AND SYSTEMIC ADVERSE EVENTS

AE, adverse event; IIV4, egg-based quadrivalent influenza vaccine; ccIIV4, cell-based quadrivalent influenza vaccine

27.9

2.2

25.8

0.4

17.3

0.4

10.7

0.1

27.9

3.1

26.9

2.1

17.4

1.5

17.9

1.6

6.8

0.6

6.8

0.6

3.2

0.2

30.0

1.4

24.6

0.0

15.9

0.0

10.8

0.0

29.6

2.7

25.5

1.4

17.6

1.7

16.3

1.0

6.9

0.1

6.3

0.5

3.4

0.0

0

5

10

15

20

25

30

35

40

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Participants reporting

solicited AEs, %

ccIIV4 IIV4

• Erythema and tenderness were the most common solicited local AEs

• Sleepiness and irritability were the most common solicited systemic AEs

• Most AEs were mild or moderate in severity

• Safety and tolerability were similar between the two vaccine groups

Any Severe

Tenderness

Any Severe Any Severe Any Severe Any Severe Any Severe Any Severe Any Severe ≥38°C ≥40°C Any Severe Any Severe

Erythema Induration Ecchymosis Irritability Sleepiness Change of

eating habits

Diarrhea Fever Vomiting Shivering

Solicited local AEs Solicited systemic AEs
13 |

SAFETY AND TOLERABILITY SUMMARY

UNSOLICITED ADVERSE EVENTS

aDay 57 and Day 209 in participants not previously vaccinated

AE, adverse event; NOCD, new onset of chronic disease; IIV4, egg-based quadrivalent influenza vaccine; ccIIV4, cell-based 

quadrivalent influenza vaccine; SAE, serious adverse event.

26.2

4.4

0.9 1.4 0.2 0.1

25.7

4.5

0.9 1.6

0.0 0.0

0

5

10

15

20

25

30

1 2 3 4 5 6

Participants reporting

unsolicited systemic AEs, %

• Similar proportions of participants in the ccIIV4 and IIV4 groups reported at least one unsolicited AE

• Adverse events leading to withdrawal were reported by three participants in the ccIIV4 group 

Any AE Vaccine-related 

AE

SAE NOCD Leading to study 

withdrawal

Death

Day 1–29/57a Day 1–181/209a
14 |

FLUCELVAX QUADRIVALENT (ccIIV4) Phase III

Immunogenicity & Safety in 6 through 47 months

• SUMMARY

• ccIIV4 met all of the predefined non-inferiority criteria for 

immunogenicity as compared to IIV4

• Immunogenicity data consistent against all four strains

• ccIIV4 was well tolerated, with similar rates of solicited and 

unsolicited adverse events between the two vaccination 

groups, consistent with previously reported data in older 

children