NCT01884519

Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Influenza Vaccine, Fluarix®/Influsplit SSW® (2013/2014 Season), in Adults 18 Years of Age and Older

Completed Phase 3 Results posted Last updated 7 September 2018

What this trial tests

Phase 3 trial testing Fluarix/Influsplit SSW® (2013-2014 season) in Influenza in 120 participants. Completed in 2 August 2013.

Timeline

1 July 2013

Primary endpoint
2 August 2013

2 August 2013

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	120
Start date	1 July 2013
Primary completion	2 August 2013
Estimated completion	2 August 2013
Sites	4 locations across Germany

Drugs / interventions tested

• Fluarix/Influsplit SSW® (2013-2014 season) — full drug profile →

Conditions studied

• Influenza — all drugs for Influenza →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Influenza. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Influenza Strains Primary · At Day 0 and Day 21

Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata).

H1N1, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	27.3	20.3 – 36.8
Fluarix/Influsplit > 60 Years Group	15.7	12.1 – 20.4

H1N1, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	444.6	335.6 – 588.9
Fluarix/Influsplit > 60 Years Group	197.0	142.6 – 272.1

H3N2, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	15.8	11.9 – 21.1
Fluarix/Influsplit > 60 Years Group	14.2	11.0 – 18.4

H3N2, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	73.8	57.8 – 94.2
Fluarix/Influsplit > 60 Years Group	80.0	58.4 – 109.5

Yamagata, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	105.0	83.6 – 131.8
Fluarix/Influsplit > 60 Years Group	95.2	77.5 – 116.9

Yamagata, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	424.6	347.6 – 518.8
Fluarix/Influsplit > 60 Years Group	327.5	266.2 – 402.9

Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the Three Vaccine Influenza Strains. Primary · At Day 0 and Day 21

A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata).

H1N1, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	25
Fluarix/Influsplit > 60 Years Group	14

H1N1, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	58
Fluarix/Influsplit > 60 Years Group	56

H3N2, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	12
Fluarix/Influsplit > 60 Years Group	12

H3N2, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	50
Fluarix/Influsplit > 60 Years Group	44

Yamagata, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	53
Fluarix/Influsplit > 60 Years Group	55

Yamagata, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	60
Fluarix/Influsplit > 60 Years Group	60

Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the Three Vaccine Influenza Strains. Primary · At Day 21

A seroconverted subjects was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata).

H1N1

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	44
Fluarix/Influsplit > 60 Years Group	46

H3N2

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	31
Fluarix/Influsplit > 60 Years Group	29

Yamagata

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	30
Fluarix/Influsplit > 60 Years Group	23

Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Three Vaccine Influenza Strains. Primary · At Day 21

MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata).

H1N1

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	16.3	10.8 – 24.5
Fluarix/Influsplit > 60 Years Group	12.6	8.7 – 18.2

H3N2

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	4.7	3.4 – 6.4
Fluarix/Influsplit > 60 Years Group	5.6	4.0 – 7.9

Yamagata

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	4.0	3.1 – 5.3
Fluarix/Influsplit > 60 Years Group	3.4	2.7 – 4.3

Number of Subjects With Seroprotection Power (SPP) for HI Antibody Titer Against Each of the Three Vaccine Influenza Strains Above the Cut-off Value. Primary · At Day 21

SPP was defined as the number of vaccinated subjects with a pre-vaccination titer \< 1:40 and a post-vaccination titer ≥ 1:40. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata).

H1N1 [N=35,46]

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	33
Fluarix/Influsplit > 60 Years Group	42

H3N2 [N=48,48]

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	38
Fluarix/Influsplit > 60 Years Group	32

Yamagata [N=7,5]

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	7
Fluarix/Influsplit > 60 Years Group	5

Humoral Immune Response in Terms of HI Antibody Titers Against Each of the Three Vaccine Influenza Strains Secondary · At Days 0 and 21

Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and \>60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013.

H1N1, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	28.7	17.2 – 48.1
Fluarix/Influsplit 18-60 Years Group Without Vaccination	26.6	18.2 – 38.9
Fluarix/Influsplit > 60 Years Group With Vaccination	16.3	10.5 – 25.2
Fluarix/Influsplit > 60 Years Group Without Vaccination	15.1	10.9 – 21.0

H1N1, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	348.8	200.3 – 607.4
Fluarix/Influsplit 18-60 Years Group Without Vaccination	501.9	361.0 – 698.0
Fluarix/Influsplit > 60 Years Group With Vaccination	158.2	99.1 – 252.5
Fluarix/Influsplit > 60 Years Group Without Vaccination	241.9	152.7 – 383.3

H3N2, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	18.6	10.8 – 32.0
Fluarix/Influsplit 18-60 Years Group Without Vaccination	14.6	10.3 – 20.8
Fluarix/Influsplit > 60 Years Group With Vaccination	17.3	11.4 – 26.2
Fluarix/Influsplit > 60 Years Group Without Vaccination	11.8	8.6 – 16.2

H3N2, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	60.6	39.3 – 93.5
Fluarix/Influsplit 18-60 Years Group Without Vaccination	81.4	60.0 – 110.4
Fluarix/Influsplit > 60 Years Group With Vaccination	58.6	39.9 – 86.2
Fluarix/Influsplit > 60 Years Group Without Vaccination	106.9	65.6 – 174.3

Yamagata, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	109.3	74.3 – 160.9
Fluarix/Influsplit 18-60 Years Group Without Vaccination	102.9	76.7 – 138.0
Fluarix/Influsplit > 60 Years Group With Vaccination	110.6	84.6 – 144.5
Fluarix/Influsplit > 60 Years Group Without Vaccination	82.7	60.3 – 113.4

Yamagata, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	355.0	247.3 – 509.5
Fluarix/Influsplit 18-60 Years Group Without Vaccination	464.4	362.9 – 594.2
Fluarix/Influsplit > 60 Years Group With Vaccination	237.3	184.2 – 305.8
Fluarix/Influsplit > 60 Years Group Without Vaccination	442.6	328.9 – 595.7

Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the Three Vaccine Influenza Strains. Secondary · At Day 0 and Day 21

A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and \>60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013.

H1N1, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	9
Fluarix/Influsplit 18-60 Years Group Without Vaccination	16
Fluarix/Influsplit > 60 Years Group With Vaccination	8
Fluarix/Influsplit > 60 Years Group Without Vaccination	6

H1N1, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	19
Fluarix/Influsplit 18-60 Years Group Without Vaccination	39
Fluarix/Influsplit > 60 Years Group With Vaccination	26
Fluarix/Influsplit > 60 Years Group Without Vaccination	30

H3N2, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	5
Fluarix/Influsplit 18-60 Years Group Without Vaccination	7
Fluarix/Influsplit > 60 Years Group With Vaccination	6
Fluarix/Influsplit > 60 Years Group Without Vaccination	6

H3N2, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	16
Fluarix/Influsplit 18-60 Years Group Without Vaccination	34
Fluarix/Influsplit > 60 Years Group With Vaccination	20
Fluarix/Influsplit > 60 Years Group Without Vaccination	24

Yamagata, Day 0

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	18
Fluarix/Influsplit 18-60 Years Group Without Vaccination	35
Fluarix/Influsplit > 60 Years Group With Vaccination	29
Fluarix/Influsplit > 60 Years Group Without Vaccination	26

Yamagata, Day 21

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	20
Fluarix/Influsplit 18-60 Years Group Without Vaccination	40
Fluarix/Influsplit > 60 Years Group With Vaccination	29
Fluarix/Influsplit > 60 Years Group Without Vaccination	31

Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the Three Vaccine Influenza Strains. Secondary · At Day 21

A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and \>60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/201

H1N1

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	13
Fluarix/Influsplit 18-60 Years Group Without Vaccination	31
Fluarix/Influsplit > 60 Years Group With Vaccination	20
Fluarix/Influsplit > 60 Years Group Without Vaccination	26

H3N2

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	8
Fluarix/Influsplit 18-60 Years Group Without Vaccination	23
Fluarix/Influsplit > 60 Years Group With Vaccination	10
Fluarix/Influsplit > 60 Years Group Without Vaccination	19

Yamagata

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	6
Fluarix/Influsplit 18-60 Years Group Without Vaccination	24
Fluarix/Influsplit > 60 Years Group With Vaccination	5
Fluarix/Influsplit > 60 Years Group Without Vaccination	18

Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Three Vaccine Influenza Strains. Secondary · At Day 21

MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and \>60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013.

H1N1

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	12.1	5.8 – 25.4
Fluarix/Influsplit 18-60 Years Group Without Vaccination	18.9	11.4 – 31.4
Fluarix/Influsplit > 60 Years Group With Vaccinationars Group	9.7	5.5 – 17.0
Fluarix/Influsplit > 60 Years Group Without Vaccination	16.0	9.7 – 26.5

H3N2

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	3.3	2.0 – 5.2
Fluarix/Influsplit 18-60 Years Group Without Vaccination	5.6	3.7 – 8.3
Fluarix/Influsplit > 60 Years Group With Vaccinationars Group	3.4	2.4 – 4.8
Fluarix/Influsplit > 60 Years Group Without Vaccination	9.1	5.3 – 15.5

Yamagata

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group With Vaccination	3.2	2.0 – 5.2
Fluarix/Influsplit 18-60 Years Group Without Vaccination	4.5	3.2 – 6.3
Fluarix/Influsplit > 60 Years Group With Vaccinationars Group	2.1	1.7 – 2.7
Fluarix/Influsplit > 60 Years Group Without Vaccination	5.4	3.9 – 7.4

Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. Secondary · During the 4-day (Days 0-3) post-vaccination period

Solicited local symptoms assessed were ecchymosis, induration, pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 ecchymosis, induration, redness and swelling was greater than 100 millimeters (mm) i.e. \>100mm.

Any Ecchymosis

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Grade 3 Ecchymosis

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Any Induration

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	2

Grade 3 Induration

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Any Pain

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	38
Fluarix/Influsplit > 60 Years Group	15

Grade 3 Pain

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Any Redness

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	8
Fluarix/Influsplit > 60 Years Group	3

Grade 3 Redness

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Duration of Solicited Local Symptoms. Secondary · During the 4-day (Days 0-3) post-vaccination period

Duration was defined as number of days with any grade of local symptoms.

Induration [N=0,2]

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0.0	0.0 – 0.0
Fluarix/Influsplit > 60 Years Group	1.5	1.0 – 2.0

Pain [N=38, 15]

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	2.0	1.0 – 4.0
Fluarix/Influsplit > 60 Years Group	2.0	1.0 – 4.0

Redness [N=8,3]

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	2.0	1.0 – 4.0
Fluarix/Influsplit > 60 Years Group	2.0	2.0 – 4.0

Swelling [N=6,2]

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	1.0	1.0 – 4.0
Fluarix/Influsplit > 60 Years Group	2.0	2.0 – 2.0

Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. Secondary · During the 4-day (Days 0-3) post-vaccination period

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, increased sweating and fever \[axillary temperature above 37.5 degrees Celsius (°C)\]. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C

Any Arthralgia

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	5
Fluarix/Influsplit > 60 Years Group	5

Grade 3 Arthralgia

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Related Arthralgia

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	4
Fluarix/Influsplit > 60 Years Group	3

Any Fatigue

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	10
Fluarix/Influsplit > 60 Years Group	7

Grade 3 Fatigue

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Related Fatigue

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	6
Fluarix/Influsplit > 60 Years Group	4

Any Gastrointestinal symptoms

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	4
Fluarix/Influsplit > 60 Years Group	1

Grade 3 Gastrointestinal symptoms

Group	Value	95% CI
Fluarix/Influsplit 18-60 Years Group	0
Fluarix/Influsplit > 60 Years Group	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious Adverse Events: From Day 0 to Day 180; Solicited local and general symptoms: During the 4-day (Days 0-3) post-vaccination period; Unsolicited symptoms: During the 21-day (Day 0-20) post-vaccination period. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fluarix/Influsplit 18-60 Years Group

Serious: 0/60 (0%)

Deaths: —

Fluarix/Influsplit > 60 Years Group

Serious: 0/60 (0%)

Deaths: —

Other adverse events (10 terms — click to expand)

Reaction	System	Fluarix/Influsplit 18-60 Y…	Fluarix/Influsplit > 60 Ye…
Pain	General disorders	—	—
Myalgia	General disorders	—	—
Fatigue	General disorders	—	—
Headache	General disorders	—	—
Redness	General disorders	—	—
Sweating	General disorders	—	—
Swelling	General disorders	—	—
Arthralgia	General disorders	—	—
Gastrointestinal symptoms	General disorders	—	—
Shivering	General disorders	—	—

Data from ClinicalTrials.gov NCT01884519 adverse events section.

Sponsor's own description

The purpose of this study is to assess, in adults 18 years of age and above, the immunogenicity and reactogenicity of the seasonal influenza vaccine, Fluarix/Influsplit SSW 2013/2014, containing the three vaccine influenza strains (two A strains and one B strain) for the 2013/2014 season.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.