Trial Outcomes & Findings for Safety and Immunogenicity of a Subunit Trivalent Influenza Vaccine, Northern Hemisphere Formulation 2013/2014, Including MF59C.1 Adjuvant, in Healthy Adults ≥65 Years of Age (NCT NCT01879540)

NCT ID: NCT01879540

Last Updated: 2014-03-26

Results Overview

Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of aTIV. The related European Committee for Human Medicinal Products (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is \>60%.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: Day 1 (baseline) and Day 22
• Results posted on: 2014-03-26

Participant Flow

Participant milestones

Measure	aTIV Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Overall Study STARTED	63
Overall Study COMPLETED	63
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Immunogenicity of a Subunit Trivalent Influenza Vaccine, Northern Hemisphere Formulation 2013/2014, Including MF59C.1 Adjuvant, in Healthy Adults ≥65 Years of Age

Baseline characteristics by cohort

Measure	aTIV n=63 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Age, Continuous	71.9 year STANDARD_DEVIATION 5.0 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (baseline) and Day 22

Population: Analysis was done on the per-protocol population i.e all subjects who have received study vaccination and provided immunogenicity data both at baseline and after vaccination; did not withdraw informed consent and did not have Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) confirmed influenza during the study.

Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of aTIV.

The related European Committee for Human Medicinal Products (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >60%.

Outcome measures

Measure	aTIV n=61 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV Day 22 (B strain)	79 Percentage of subjects Interval 66.0 to 88.0
Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV Day 1 (H1N1 strain)	46 Percentage of subjects Interval 33.0 to 59.0
Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV Day 22 (H1N1 strain)	89 Percentage of subjects Interval 78.0 to 95.0
Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV Day 1 (H3N2 strain)	43 Percentage of subjects Interval 30.0 to 56.0
Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV Day 22 (H3N2 strain)	90 Percentage of subjects Interval 80.0 to 96.0
Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV Day 1 (B strain)	28 Percentage of subjects Interval 17.0 to 41.0

PRIMARY outcome

Timeframe: Day 22

Population: Analysis was done on the per-protocol population

Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age achieving seroconversion or significant increase in SRH area against each of the three vaccine strains, three weeks after receiving one dose of aTIV.

Seroconversion is defined as percentage of subjects with a pre-vaccination SRH area ≤4mm2 achieving a post-vaccination SRH area ≥25 mm2. Significant increase is defined as percentage of subjects with a pre-vaccination SRH area >4mm2 achieving at least 50% increase in post-vaccination SRH area.

The related European (CHMP) criterion for the assessment of immunogenicity is met if>30% of subjects achieve seroconversion or significant increase in post-vaccination SRH area.

Outcome measures

Measure	aTIV n=61 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H1N1 strain	57 Percentage of subjects Interval 44.0 to 70.0
Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H3N2 strain	61 Percentage of subjects Interval 47.0 to 73.0
Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV B strain	70 Percentage of subjects Interval 57.0 to 81.0

PRIMARY outcome

Timeframe: Day 22/Day 1

Population: Analysis was done on the per-protocol population

The antibody responses following one dose of aTIV were evaluated in terms of geometric mean ratio GMRs of post vaccination GMAs to pre vaccination GMAs against each of the three vaccine strains, three weeks after receiving one dose of aTIV.

The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is > 2.0.

Outcome measures

Measure	aTIV n=61 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H1N1 strain	2.63 Ratio Interval 2.04 to 3.39
Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H3N2 strain	2.34 Ratio Interval 1.91 to 2.87
Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), Against Each of Three Vaccine Strains After Receiving One Dose of aTIV B strain	2.89 Ratio Interval 2.35 to 3.57

PRIMARY outcome

Timeframe: Day 1 (baseline) and Day 22

Population: Analysis was done on the per-protocol population

Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age with HI titers ≥40, against each of the three vaccine strains, three weeks after receiving one dose of aTIV.

The related European (CHMP) criterion for the assessment of immunogenicity is met if the of subjects achieving HI titers ≥ 40 is >60%.

Outcome measures

Measure	aTIV n=61 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Percentages of Subjects With Haemagglutinin Inhibition(HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV. Day 1 (H1N1 strain)	75 Percentage of subjects Interval 63.0 to 86.0
Percentages of Subjects With Haemagglutinin Inhibition(HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV. Day 22 (H1N1 strain)	97 Percentage of subjects Interval 89.0 to 100.0
Percentages of Subjects With Haemagglutinin Inhibition(HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV. Day 1 (H3N2 strain)	89 Percentage of subjects Interval 78.0 to 95.0
Percentages of Subjects With Haemagglutinin Inhibition(HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV. Day 22 (H3N2 strain)	100 Percentage of subjects Interval 94.0 to 100.0
Percentages of Subjects With Haemagglutinin Inhibition(HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV. Day 1 (B strain)	61 Percentage of subjects Interval 47.0 to 73.0
Percentages of Subjects With Haemagglutinin Inhibition(HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV. Day 22 (B strain)	98 Percentage of subjects Interval 91.0 to 100.0

PRIMARY outcome

Timeframe: Day 22

Population: Analysis was done on the per-protocol population

Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age achieving seroconversion or significant increase in HI antibody titers after receiving one dose of aTIV.

Seroconversion is defined as percentage of subjects with a pre-vaccination HI titer <10 to a post-vaccination titer ≥40. Significant increase is defined as percentage of subjects with a pre-vaccination HI titer ≥10 to at least a 4-fold increase in post-vaccination HI antibody titers.

The related European (CHMP) criterion for the assessment of immunogenicity is met if >30% of subjects achieve seroconversion or significant increase in post-vaccination HI titers.

Outcome measures

Measure	aTIV n=61 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H1N1 strain	39 Percentage of subjects Interval 27.0 to 53.0
Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H3N2 strain	43 Percentage of subjects Interval 30.0 to 56.0
Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV B strain	38 Percentage of subjects Interval 26.0 to 51.0

PRIMARY outcome

Timeframe: Day 22/Day 1

Population: Analysis was done on the per-protocol population

The antibody responses following one dose of aTIV were evaluated in terms of GMRs of post vaccination geometric mean HI titers against each of the three vaccine strains, three weeks after receiving one dose of aTIV.

The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is > 2.0.

Outcome measures

Measure	aTIV n=61 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination HI Titers, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H1N1 strain	3.57 Ratio Interval 2.59 to 4.91
Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination HI Titers, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV H3N2 strain	3.32 Ratio Interval 2.45 to 4.49
Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination HI Titers, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV B strain	2.69 Ratio Interval 2.22 to 3.26

PRIMARY outcome

Timeframe: Day 1 to Day 4 post vaccination

Population: Analysis was done on the safety set population i.e all subjects who have post-vaccination AE or reactogenicity records

The number of adult subjects ≥65 years of age reporting solicited local and systemic adverse events and other solicited adverse events after receiving one dose of aTIV are reported.

Outcome measures

Measure	aTIV n=63 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Injection site erythema	3 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Any Local	26 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Injection site induration	2 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Injection site ecchymosis	2 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Injection site pain	21 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Any systemic	15 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Chills/shivering	1 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Malaise	2 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Myalgia	2 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Arthralgia	1 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Fatigue	11 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Headache	5 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Fever (≥ 38°C)	0 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Temperature ≥40°C	0 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Prophylactic use of analgesics/antipyretics (N=61)	0 Participants
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of aTIV Therapeutic use of analgesics/antipyretics (N=61)	2 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 22 post-vaccination

Population: Analysis was done on the unsolicited safety set population i.e all subjects who had post-vaccination unsolicited AE records

The number of adult subjects ≥65 years of age subjects reporting any unsolicited adverse event (AEs) between Day 1 to 4 and serious adverse events (SAEs), medically attended AEs, AEs leading to withdrawal from the study between Day 1 to Day 22 after receiving one dose of aTIV are reported.

Outcome measures

Measure	aTIV n=63 Participants Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of aTIV Serious AEs	0 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of aTIV Any AE	12 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of aTIV At least possibly related AEs	10 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of aTIV At least possibly related SAEs	0 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of aTIV Medically attended AEs	5 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of aTIV AEs leading to withdrawal	0 Participants
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of aTIV Death	0 Participants

Adverse Events

aTIV

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	aTIV n=63 participants at risk Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere
General disorders Fatigue	17.5% 11/63 • All solicited AEs and unsolicited AEs were collected from Day 1 to Day 4; all unsolicited SAEs, medically attended AEs, AEs leading to withdrawal from the study were collected from Day 1 to Day 22
General disorders Injection site erythema	7.9% 5/63 • All solicited AEs and unsolicited AEs were collected from Day 1 to Day 4; all unsolicited SAEs, medically attended AEs, AEs leading to withdrawal from the study were collected from Day 1 to Day 22
General disorders Injection site pain	33.3% 21/63 • All solicited AEs and unsolicited AEs were collected from Day 1 to Day 4; all unsolicited SAEs, medically attended AEs, AEs leading to withdrawal from the study were collected from Day 1 to Day 22
Nervous system disorders Headache	7.9% 5/63 • All solicited AEs and unsolicited AEs were collected from Day 1 to Day 4; all unsolicited SAEs, medically attended AEs, AEs leading to withdrawal from the study were collected from Day 1 to Day 22

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: RegistryContactVaccinesUS@novartis.com

Results disclosure agreements

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

Restriction type: LTE60