Trial Outcomes & Findings for Safety and Immunogenicity of Flublok Quadrivalent vs IIV4 in Adults 18-49 Years of Age (NCT NCT02290509)

Last Updated: 2016-10-27

Results Overview

Seroconversion is defined as: Either a pre vaccination titer \< 10 (1/dil) and a post vaccination titer ≥ 40 (1/dil), or a pre vaccination titer ≥ 10 (1/dil) and a ≥ 4 fold increase in post vaccination titer at Day 28 after the final vaccination.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1350 participants

Primary outcome timeframe

Day 28 after final vaccination

Results posted on

2016-10-27

Participant Flow

Participant milestones

Participant milestones
Measure	Flublok Quadrivalent Influenza Vaccine Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine
Overall Study STARTED	1011	339
Overall Study COMPLETED	962	325
Overall Study NOT COMPLETED	49	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Immunogenicity of Flublok Quadrivalent vs IIV4 in Adults 18-49 Years of Age

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Flublok Quadrivalent Influenza Vaccine n=998 Participants Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) n=332 Participants Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine	Total n=1330 Participants Total of all reporting groups
Age, Customized 18-49 years	998 participants n=5 Participants	332 participants n=7 Participants	1330 participants n=5 Participants
Sex: Female, Male Female	639 Participants n=5 Participants	222 Participants n=7 Participants	861 Participants n=5 Participants
Sex: Female, Male Male	359 Participants n=5 Participants	110 Participants n=7 Participants	469 Participants n=5 Participants
Region of Enrollment United States	998 participants n=5 Participants	332 participants n=7 Participants	1330 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28 after final vaccination

Population: The immunogenicity population includes all randomized subjects who received a dose of study vaccine, provided serum samples for baseline (Day 0) and Day 28 HAI titers (within the specified windows) and have no major protocol deviations that might have adversely affect the immune response.

Outcome measures

Outcome measures
Measure	Flublok Quadrivalent Influenza Vaccine n=969 Participants Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) n=323 Participants Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine
Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine A/H1N1/California	66.7 percentage of participants Interval 63.6 to 69.6	63.5 percentage of participants Interval 58.0 to 68.7
Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine B/Brisbane	40.6 percentage of participants Interval 37.4 to 43.7	58.2 percentage of participants Interval 52.6 to 63.6
Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine A/H3N2/Texas	72.1 percentage of participants Interval 69.2 to 74.9	57.0 percentage of participants Interval 51.4 to 62.4
Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine B/Massachusetts	59.6 percentage of participants Interval 56.5 to 62.8	60.4 percentage of participants Interval 54.8 to 65.7

PRIMARY outcome

Timeframe: Day 0 and Day 28 after final vaccination

Immunogenicity will be evaluated prior to vaccination and at 28 days after vaccination using the hemagglutination inhibition (HAI) technique. For each influenza vaccine strain, pre and post vaccination geometric mean titers (GMTs) were calculated.

Outcome measures

Outcome measures
Measure	Flublok Quadrivalent Influenza Vaccine n=969 Participants Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) n=323 Participants Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 0 - A/H3N2/Texas	75 titer Interval 68.0 to 83.0	70 titer Interval 60.0 to 82.0
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 28 - A/H3N2/Texas	757 titer Interval 709.0 to 808.0	385 titer Interval 348.0 to 425.0
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 0 - B/Massachusetts	27 titer Interval 25.0 to 29.0	24 titer Interval 21.0 to 28.0
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 28 - B/Massachusetts	159 titer Interval 147.0 to 171.0	136 titer Interval 121.0 to 153.0
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 0 - A/H1N1/California	60 titer Interval 54.0 to 65.0	54 titer Interval 46.0 to 63.0
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 28 - A/H1N1/California	502 titer Interval 469.0 to 537.0	407 titer Interval 367.0 to 451.0
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 0 - B/Brisbane	12 titer Interval 11.0 to 13.0	11 titer Interval 10.0 to 12.0
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine Day 28 - B/Brisbane	43 titer Interval 40.0 to 46.0	64 titer Interval 58.0 to 72.0

SECONDARY outcome

Timeframe: Days 0-7

Population: The Reactogenicity Population includes subjects who recorded any systemic reaction data and injection site reaction data following administration of study vaccine. This was two subjects less than the Safety Population.

Outcome measures

Outcome measures
Measure	Flublok Quadrivalent Influenza Vaccine n=996 Participants Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) n=332 Participants Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine
Number of Participants With Systemic and Injection Site Reactogenicity Subjects with one or more injection site reaction	510 participants	172 participants
Number of Participants With Systemic and Injection Site Reactogenicity Subjects with one or more systemic reaction event	339 participants	119 participants

SECONDARY outcome

Timeframe: Six months post-vaccination

Population: The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.

Outcome measures

Outcome measures
Measure	Flublok Quadrivalent Influenza Vaccine n=998 Participants Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) n=332 Participants Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine
Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) Serious adverse events (SAEs)	10 participants	2 participants
Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) Medically-attended adverse events (MAEs)	80 participants	24 participants

Adverse Events

Flublok Quadrivalent Influenza Vaccine

Serious events: 10 serious events

Other events: 63 other events

Deaths: 0 deaths

Inactivated Influenza Vaccine (IIV4)

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Flublok Quadrivalent Influenza Vaccine n=998 participants at risk Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) n=332 participants at risk Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.30% 1/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Gastrointestinal disorders Pancreatitis	0.00% 0/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.30% 1/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Gastrointestinal disorders Small intestinal obstruction	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Cardiac disorders Myocardial infarction	0.20% 2/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Infections and infestations Appendicitis	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Infections and infestations Periumbilical abcess	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Hepatobiliary disorders Cholecystitis	0.00% 0/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.30% 1/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Injury, poisoning and procedural complications Road traffic accident	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Musculoskeletal and connective tissue disorders Neck pain	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Nervous system disorders Metabolic encephalopathy	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Reproductive system and breast disorders Ovarian cyst	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Surgical and medical procedures Arm amputation	0.10% 1/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	0.00% 0/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.

Other adverse events

Other adverse events
Measure	Flublok Quadrivalent Influenza Vaccine n=998 participants at risk Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL Flublok Quadrivalent: Intramuscular injection of study vaccine	Inactivated Influenza Vaccine (IIV4) n=332 participants at risk Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL. Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine
Infections and infestations Nasophayngitis	1.3% 13/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	1.5% 5/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Infections and infestations Upper respiratory tract infection	1.0% 10/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	1.5% 5/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Infections and infestations Sinusitis	0.60% 6/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	1.5% 5/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Respiratory, thoracic and mediastinal disorders Cough	1.4% 14/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	1.2% 4/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
Nervous system disorders Headache	2.0% 20/998 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.	1.5% 5/332 • All AEs collected 28 days after study immunization and all Serious Adverse Events (SAEs) collected through six (6) months after study immunization. The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.

Additional Information

Lisa M. Dunkle, M.D., Chief Medical Officer

Protein Sciences Corporation

Phone: 203-599-6064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60