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Clinical Trial Results:
A Phase 3, Randomized, Active-Controlled, Observer-Blinded Trial to Assess the Lot Consistency, Safety, Tolerability, and Immunogenicity of a Meningococcal Serogroup B Bivalent rLP2086 Vaccine in Healthy Subjects Aged ≥10 to <19 Years

Summary
EudraCT number	2010-023873-20
Trial protocol	DE HU FI CZ GB ES PL IT Outside EU/EEA
Global end of trial date	14 Apr 2015

Results information
Results version number	v1(current)
This version publication date	19 Nov 2016
First version publication date	19 Nov 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

B1971009

ISRCTN number

US NCT number

NCT01830855

WHO universal trial number (UTN)

Other trial identifiers

Alias: 6108A1-3001

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001037-PIP02-11

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

07 Oct 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Apr 2015

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety profile of bivalent recombinant lipoprotein 2086 (rLP2086) vaccine compared to a control (hepatitis A virus [HAV]/saline), as measured by local reactions, systemic events, adverse events (AEs), serious AEs, newly diagnosed chronic medical conditions, medically attended AEs, and immediate AEs. To assess the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 4 primary Neisseria meningitidis serogroup B (MnB) test strains, 2 expressing an LP2086 subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the third vaccination with bivalent rLP2086 vaccine. To demonstrate that the immune responses induced by 3 lots of bivalent rLP2086 vaccine are equivalent as measured by hSBA performed with 2 primary MnB test strains, 1 expressing an LP2086 subfamily A protein and 1 expressing an LP2086 subfamily B protein, 1 month after the third vaccination with bivalent rLP2086 vaccine.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Apr 2013

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 114

Country: Number of subjects enrolled

Czech Republic: 116

Country: Number of subjects enrolled

Finland: 589

Country: Number of subjects enrolled

Germany: 184

Country: Number of subjects enrolled

Italy: 184

Country: Number of subjects enrolled

Poland: 439

Country: Number of subjects enrolled

United States: 1805

Country: Number of subjects enrolled

United Kingdom: 159

Worldwide total number of subjects

3590

EEA total number of subjects

1671

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

849

Adolescents (12-17 years)

2346

Adults (18-64 years)

395

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 3596 subjects were randomized in this study, out of which 3590 subjects received vaccination.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Group 1 rLP2086 Lot 1

Arm description

Lot 1 on a 0-, 2-, 6- month schedule.

Arm type

Experimental

Investigational medicinal product name

rLP2086 Lot 1

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 1 dose of 0.5 milliliter (mL) of bivalent rLP2086 Lot 1 0-, 2-, and 6-month schedule.

Group 2 rLP2086 Lot 2

Arm description

Lot 2 on a 0-, 2-, 6- month schedule.

Arm type

Experimental

Investigational medicinal product name

rLP2086 Lot 2

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 1 dose of 0.5 mL of bivalent rLP2086 Lot 2 0-, 2-, and 6-month schedule.

Group 3 rLP2086 Lot 3

Arm description

Lot 3 on a 0-, 2-, 6- month schedule.

Arm type

Experimental

Investigational medicinal product name

rLP2086 Lot 3

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 1 dose of 0.5 mL of bivalent rLP2086 Lot 3 on 0-, 2-, and 6-month schedule.

Group 4 HAV/Saline

Arm description

Hepatitis A virus vaccine (HAV) on a 0- and 6-month schedule and saline at Month 2.

Arm type

Active comparator

Investigational medicinal product name

HAV

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 1 dose 0.5 mL of HAV on 0- and 6-month schedule.

Investigational medicinal product name

Saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received 1 dose 0.5 mL of saline at Month 2.

Number of subjects in period 1	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3	Group 4 HAV/Saline
Started	1508	598	587	897
Completed	1353	537	521	815
Not completed	155	61	66	82
Consent withdrawn by subject	33	14	10	12
Adverse Event	11	5	6	3
No longer meets eligibility criteria	11	2	3	5
Protocol deviation	10	5	6	6
Pregnancy	3	1	2	1
No longer willing to participate	32	13	12	17
Unspecified	7	1	4	4
Medication error without associated AE	1	-	-	1
Lost to follow-up	47	20	23	33

Baseline characteristics

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Reporting group title

Group 1 rLP2086 Lot 1

Reporting group description

Lot 1 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 2 rLP2086 Lot 2

Reporting group description

Lot 2 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 3 rLP2086 Lot 3

Reporting group description

Lot 3 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 4 HAV/Saline

Reporting group description

Hepatitis A virus vaccine (HAV) on a 0- and 6-month schedule and saline at Month 2.

Reporting group values	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3	Group 4 HAV/Saline	Total
Number of subjects	1508	598	587	897	3590
Age categorical
Units: Subjects
2-11 years	356	136	135	222	849
12-17 years	995	389	382	580	2346
18-64 years	157	73	70	95	395
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	13.9 ± 2.6	14 ± 2.6	13.9 ± 2.6	13.9 ± 2.6	-
Gender, Male/Female
Units: Participants
Female	737	286	274	443	1740
Male	771	312	313	454	1850

End points

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Reporting group title

Group 1 rLP2086 Lot 1

Reporting group description

Lot 1 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 2 rLP2086 Lot 2

Reporting group description

Lot 2 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 3 rLP2086 Lot 3

Reporting group description

Lot 3 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 4 HAV/Saline

Reporting group description

Hepatitis A virus vaccine (HAV) on a 0- and 6-month schedule and saline at Month 2.

Subject analysis set title

rLP2086 (Lots 1-3)

Subject analysis set type

Safety analysis

Subject analysis set description

Commercial lots 1, 2 and 3 on a 0-, 2-, 6-months schedule.

Subject analysis set title

Group 4 HAV/Saline

Subject analysis set type

Safety analysis

Subject analysis set description

Hepatitis A virus vaccine (HAV) on a 0- and 6-month schedule and saline at Month 2.

Primary: Percentage of Subjects with >=4 Fold Rise in Serum Bactericidal Assay Using Human Complement (hSBA) for 4 Primary Strains and Composite Response (hSBA >=Lower Limit of Quantification [LLOQ] for all 4 Primary Strains Combined)

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End point title

Percentage of Subjects with >=4 Fold Rise in Serum Bactericidal Assay Using Human Complement (hSBA) for 4 Primary Strains and Composite Response (hSBA >=Lower Limit of Quantification [LLOQ] for all 4 Primary Strains Combined) ^[1] ^[2]

End point description

Evaluable immunogenicity population included all eligible subjects randomized, who received correct investigational product, had pre/post vaccination blood drawn at pre-specified time points, had valid and determinate assay results for proposed analysis, received no prohibited treatment or prohibited vaccines, and had no major protocol violations. Here, N signifies subjects with valid and determinate hSBA titers for given strain at specified time point.

End point type

Primary

End point timeframe

One month after third bivalent rLP2086 vaccination

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1
Number of subjects analysed	1279
Units: percentage of subjects
number (confidence interval 95%)
Composite hSBA response (N= 1170)	83.5 (81.3 to 85.6)
PMB80[A22] (N= 1225)	83.2 (81 to 85.2)
PMB2001[A56] (N= 1128)	90.2 (88.4 to 91.9)
PMB2948[B24] (N= 1235)	79.8 (77.4 to 82)
PMB2707[B44] (N= 1203)	85.9 (83.8 to 87.8)

No statistical analyses for this end point

Primary: hSBA Geometric Mean Titers (GMTs) for Each of the 2 Primary Test Strains Measured 1 Month After the Third Vaccination with Bivalent rLP2086 Vaccine

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End point title

hSBA Geometric Mean Titers (GMTs) for Each of the 2 Primary Test Strains Measured 1 Month After the Third Vaccination with Bivalent rLP2086 Vaccine ^[3]

End point description

Evaluable immunogenicity population. Here N signifies subjects with valid and determinate hSBA titers for the given strain.

End point type

Primary

End point timeframe

One month after third bivalent rLP2086 vaccination

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3
Number of subjects analysed	1279	519	493
Units: titer
geometric mean (confidence interval 95%)
PMB80[A22] (N= 1266, 518, 492)	86.8 (82.29 to 91.5)	84.3 (77.54 to 91.68)	85.1 (78.26 to 92.47)
PMB2948[B24] (N= 1250, 516, 479)	24.1 (22.7 to 25.48)	25.3 (23.08 to 27.72)	25.2 (23.03 to 27.58)

PMB80[A22]:rLP2086 Lot 1 vs rLP2086 Lot 2

Statistical analysis description

PMB80 [A22]: The lot consistency criteria was achieved if the 95% CI for all pairwise GMRs between lots are within (0.5, 2), for the strain PMB80.

Comparison groups

Group 1 rLP2086 Lot 1 v Group 2 rLP2086 Lot 2

Number of subjects included in analysis

1798

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.14

PMB80[A22]:rLP2086 Lot 1 vs rLP2086 Lot 3

Statistical analysis description

PMB80 [A22]: The lot consistency criteria was achieved if the 95% CI for all pairwise GMRs between lots are within (0.5, 2), for the strain PMB80.

Comparison groups

Group 1 rLP2086 Lot 1 v Group 3 rLP2086 Lot 3

Number of subjects included in analysis

1772

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.13

PMB80[A22]: rLP2086 Lot 2 vs rLP2086 Lot 3

Statistical analysis description

PMB80 [A22]: The lot consistency criteria was achieved if the 95% CI for all pairwise GMRs between lots are within (0.5, 2), for the strain PMB80.

Comparison groups

Group 2 rLP2086 Lot 2 v Group 3 rLP2086 Lot 3

Number of subjects included in analysis

1012

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Ratio of GMTs

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.12

PMB2948[B24]:rLP2086 Lot 1 vs rLP2086 Lot 2

Statistical analysis description

PMB2948 [B24]: The lot consistency criteria was achieved if the 95% CI for all pairwise GMRs between lots are within (0.5, 2), for the strain PMB2948.

Comparison groups

Group 1 rLP2086 Lot 1 v Group 2 rLP2086 Lot 2

Number of subjects included in analysis

1798

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Ratio of GMTs

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.06

PMB2948[B24]: rLP2086 Lot 1 vs rLP2086 Lot 3

Statistical analysis description

PMB2948 [B24]: The lot consistency criteria was achieved if the 95% CI for all pairwise GMRs between lots are within (0.5, 2), for the strain PMB2948.

Comparison groups

Group 1 rLP2086 Lot 1 v Group 3 rLP2086 Lot 3

Number of subjects included in analysis

1772

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Ratio of GMTs

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.06

PMB2948[B24]: rLP2086 Lot 2 vs rLP2086 Lot 3

Statistical analysis description

PMB2948 [B24]: The lot consistency criteria was achieved if the 95% CI for all pairwise GMRs between lots are within (0.5, 2), for the strain PMB2948

Comparison groups

Group 2 rLP2086 Lot 2 v Group 3 rLP2086 Lot 3

Number of subjects included in analysis

1012

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.14

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After First Vaccination

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End point title

Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After First Vaccination ^[4]

End point description

Safety population for first vaccination included all subjects who received the first dose of investigational product (rLP2086 or HAV) and for whom safety information was available from first vaccination until prior to second vaccination.

End point type

Primary

End point timeframe

Within 7 days after first vaccination

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2681 ^[5]	890 ^[6]
Units: percentage of participants
number (confidence interval 95%)
Pain at injection site: Any	86.7 (85.4 to 88)	47 (43.6 to 50.3)
Pain at injection site: Mild	41.1 (39.2 to 43)	36.5 (33.3 to 39.8)
Pain at injection site: Moderate	40.7 (38.8 to 42.5)	9.9 (8 to 12)
Pain at injection site: Severe	5 (4.2 to 5.9)	0.6 (0.2 to 1.3)
Redness: Any	16.2 (14.8 to 17.7)	1.3 (0.7 to 2.3)
Redness: Mild	5.6 (4.7 to 6.5)	1.2 (0.6 to 2.2)
Redness: Moderate	8.8 (7.7 to 9.9)	0.1 (0 to 0.6)
Redness: Severe	1.9 (1.4 to 2.5)	0 (0 to 0.4)
Swelling: Any	18 (16.5 to 19.5)	2.2 (1.4 to 3.4)
Swelling: Mild	8.5 (7.4 to 9.6)	1.8 (1 to 2.9)
Swelling: Moderate	8.8 (7.7 to 9.9)	0.4 (0.1 to 1.1)
Swelling: Severe	0.7 (0.5 to 1.1)	0 (0 to 0.4)

Notes
[5] - Number of subjects analyzed signifies subjects with known values after the first vaccination.
[6] - Number of subjects analyzed signifies subjects with known values after the first vaccination.

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Second Vaccination

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End point title

Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Second Vaccination ^[7]

End point description

Safety population for second vaccination included all subjects who received the second dose of investigational product (rLP2086 or saline) and for whom safety information was available from second vaccination until prior to third vaccination.

End point type

Primary

End point timeframe

Within 7 days after second vaccination

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2545 ^[8]	843 ^[9]
Units: percentage of subjects
number (confidence interval 95%)
Pain at injection site: Any	77.7 (76 to 79.3)	15.2 (12.8 to 17.8)
Pain at injection site: Mild	39.4 (37.5 to 41.3)	12.3 (10.2 to 14.7)
Pain at injection site: Moderate	33.2 (31.4 to 35.1)	2.7 (1.7 to 4.1)
Pain at injection site: Severe	5.1 (4.2 to 6)	0.1 (0 to 0.7)
Redness: Any	12.5 (11.2 to 13.8)	0.6 (0.2 to 1.4)
Redness: Mild	5.2 (4.4 to 6.2)	0.6 (0.2 to 1.4)
Redness: Moderate	6.1 (5.2 to 7.1)	0 (0 to 0.4)
Redness: Severe	1.1 (0.8 to 1.6)	0 (0 to 0.4)
Swelling: Any	13.9 (12.5 to 15.3)	0.6 (0.2 to 1.4)
Swelling: Mild	6.3 (5.4 to 7.3)	0.5 (0.1 to 1.2)
Swelling: Moderate	7.3 (6.4 to 8.4)	0.1 (0 to 0.7)
Swelling: Severe	0.2 (0.1 to 0.5)	0 (0 to 0.4)

Notes
[8] - Number of subjects analyzed signifies subjects with known values after the second vaccination.
[9] - Number of subjects analyzed signifies subjects with known values after the second vaccination.

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Third Vaccination

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End point title

Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Third Vaccination ^[10]

End point description

Safety population for third vaccination included all subjects who received third dose of investigational product (rLP2086 or HAV) and for whom safety information was available from third vaccination until post third-vaccination blood draw.

End point type

Primary

End point timeframe

Within 7 days after third vaccination

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2421 ^[11]	821 ^[12]
Units: percentage of participants
number (confidence interval 95%)
Pain at injection site: Any	76 (74.2 to 77.7)	34 (30.7 to 37.3)
Pain at injection site: Mild	34.1 (32.2 to 36)	23.8 (20.9 to 26.8)
Pain at injection site: Moderate	36.5 (34.6 to 38.5)	9.9 (7.9 to 12.1)
Pain at injection site: Severe	5.4 (4.5 to 6.4)	0.4 (0.1 to 1.1)
Redness: Any	13.9 (12.5 to 15.3)	1.1 (0.5 to 2.1)
Redness: Mild	4.9 (4.1 to 5.8)	1 (0.4 to 1.9)
Redness: Moderate	6.8 (5.8 to 7.9)	0.1 (0 to 0.7)
Redness: Severe	2.2 (1.6 to 2.9)	0 (0 to 0.4)
Swelling: Any	15.4 (14 to 16.9)	0.9 (0.3 to 1.7)
Swelling: Mild	7.9 (6.8 to 9)	0.7 (0.3 to 1.6)
Swelling: Moderate	6.8 (5.8 to 7.9)	0.1 (0 to 0.7)
Swelling: Severe	0.7 (0.4 to 1.1)	0 (0 to 0.4)

Notes
[11] - Number of subjects analyzed signifies subjects with known values after third vaccination.
[12] - Number of subjects analyzed signifies subjects with known values after third vaccination.

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After First Vaccination

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End point title

Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After First Vaccination ^[13]

End point description

End point type

Primary

End point timeframe

Within 7 days after first vaccination

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2681 ^[14]	890 ^[15]
Units: percentage of subjects
number (confidence interval 95%)
Fever >=38 degrees C(N=2679, 890)	6.4 (5.5 to 7.4)	1.9 (1.1 to 3)
Fever 38 to <38.5degreesC(N=2679, 890)	4 (3.3 to 4.8)	1.3 (0.7 to 2.3)
Fever 38.5 to<39degreesC(N=2679, 890)	1.9 (1.5 to 2.5)	0.3 (0.1 to 1)
Fever 39 to 40degreesC(N=2679, 890)	0.5 (0.3 to 0.8)	0.2 (0 to 0.8)
Fever >40 degreesC(N=2679, 890)	0 (0 to 0.1)	0 (0 to 0.4)
Vomiting:Any(N=2681,890)	3.7 (3 to 4.5)	1.9 (1.1 to 3)
Vomiting:Mild(N=2681,890)	2.8 (2.2 to 3.5)	1.7 (0.9 to 2.8)
Vomiting:Moderate(N=2681,890)	0.9 (0.6 to 1.4)	0.2 (0 to 0.8)
Vomiting:Severe(N=2681,890)	0 (0 to 0.1)	0 (0 to 0.4)
Diarrhea:Any(N=2681,890)	10.6 (9.5 to 11.9)	12.1 (10.1 to 14.5)
Diarrhea:Mild(N=2681,890)	9.1 (8 to 10.3)	10.9 (8.9 to 13.1)
Diarrhea:Moderate(N=2681,890)	1.3 (0.9 to 1.8)	1.1 (0.5 to 2.1)
Diarrhea:Severe(N=2681,890)	0.3 (0.1 to 0.5)	0.1 (0 to 0.6)
Headache:Any(N=2681,890)	51.8 (49.9 to 53.8)	37.2 (34 to 40.5)
Headache:Mild(N=2681,890)	28.7 (27 to 30.5)	24 (21.3 to 27)
Headache:Moderate(N=2681,890)	21 (19.4 to 22.6)	12.5 (10.4 to 14.8)
Headache:Severe(N=2681,890)	2.2 (1.6 to 2.8)	0.7 (0.2 to 1.5)
Fatigue:Any(N=2681,890)	54 (52.1 to 55.9)	40.3 (37.1 to 43.6)
Fatigue:Mild(N=2681,890)	27.8 (26.1 to 29.5)	23.5 (20.7 to 26.4)
Fatigue:Moderate(N=2681,890)	23.2 (21.6 to 24.8)	15.2 (12.9 to 17.7)
Fatigue:Severe(N=2681,890)	3 (2.4 to 3.7)	1.7 (0.9 to 2.8)
Chills:Any(N=2681,890)	25.3 (23.7 to 27)	17.2 (14.8 to 19.8)
Chills:Mild(N=2681,890)	16.2 (14.8 to 17.6)	13.3 (11.1 to 15.7)
Chills:Moderate(N=2681,890)	8 (7 to 9.1)	3.5 (2.4 to 4.9)
Chills:Severe(N=2681,890)	1.2 (0.8 to 1.7)	0.4 (0.1 to 1.1)
Muscle pain:Any(N=2681,890)	24.4 (22.8 to 26.1)	19.2 (16.7 to 22)
Muscle pain:Mild(N=2681,890)	13.2 (11.9 to 14.5)	13.5 (11.3 to 15.9)
Muscle pain:Moderate(N=2681,890)	10.1 (9 to 11.3)	5.4 (4 to 7.1)
Muscle pain:Severe(N=2681,890)	1.2 (0.8 to 1.6)	0.3 (0.1 to 1)
Joint pain:Any(N=2681,890)	21.9 (20.4 to 23.5)	13.6 (11.4 to 16)
Joint pain:Mild(N=2681,890)	11.8 (10.6 to 13.1)	8.3 (6.6 to 10.3)
Joint pain:Moderate(N=2681,890)	8.7 (7.7 to 9.8)	4.6 (3.3 to 6.2)
Joint pain:Severe(N=2681,890)	1.4 (1 to 1.9)	0.7 (0.2 to 1.5)
Antipyretic medication(N=2681,890)	20.7 (19.2 to 22.3)	10.4 (8.5 to 12.6)

Notes
[14] - Number of subjects analyzed signifies subjects with known values after the first vaccination.
[15] - Number of subjects analyzed signifies subjects with known values after the first vaccination.

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Second Vaccination

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End point title

Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Second Vaccination ^[16]

End point description

End point type

Primary

End point timeframe

Within 7 days after second vaccination

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2545 ^[17]	843 ^[18]
Units: percentage of subjects
number (confidence interval 95%)
Fever >=38 degrees C(N=2540, 840)	2 (1.5 to 2.6)	1.5 (0.8 to 2.6)
Fever 38 to <38.5 degreesC(N=2540, 840)	1.2 (0.8 to 1.7)	0.7 (0.3 to 1.5)
Fever 38.5 to<39 degrees C(N=2540, 840)	0.7 (0.4 to 1.1)	0.7 (0.3 to 1.5)
Fever 39 to 40 degrees C(N=2540, 840)	0.1 (0 to 0.3)	0.1 (0 to 0.7)
Fever >40 degrees C(N=2540, 840)	0 (0 to 0.1)	0 (0 to 0.4)
Vomiting:Any(N=2545, 843)	2.2 (1.6 to 2.8)	1.4 (0.7 to 2.5)
Vomiting:Mild(N=2545, 843)	1.7 (1.3 to 2.3)	1.1 (0.5 to 2)
Vomiting:Moderate(N=2545, 843)	0.4 (0.2 to 0.8)	0.4 (0.1 to 1)
Vomiting:Severe(N=2545, 843)	0 (0 to 0.1)	0 (0 to 0.4)
Diarrhea:Any(N=2545, 843)	7.6 (6.6 to 8.7)	9.1 (7.3 to 11.3)
Diarrhea:Mild(N=2545, 843)	6.2 (5.3 to 7.2)	7.6 (5.9 to 9.6)
Diarrhea:Moderate(N=2545, 843)	1.3 (0.9 to 1.8)	1.2 (0.6 to 2.2)
Diarrhea:Severe(N=2545, 843)	0.1 (0 to 0.3)	0.4 (0.1 to 1)
Headache:Any(N=2545, 843)	37.8 (35.9 to 39.8)	28.1 (25.1 to 31.3)
Headache:Mild(N=2545, 843)	20.2 (18.7 to 21.8)	15.7 (13.3 to 18.3)
Headache:Moderate(N=2545, 843)	16 (14.6 to 17.5)	10.9 (8.9 to 13.2)
Headache:Severe(N=2545, 843)	1.7 (1.2 to 2.2)	1.5 (0.8 to 2.6)
Fatigue:Any(N=2545, 843)	38.3 (36.4 to 40.2)	26.3 (23.4 to 29.4)
Fatigue:Mild(N=2545, 843)	20.6 (19 to 22.2)	13.2 (11 to 15.6)
Fatigue:Moderate(N=2545, 843)	15.8 (14.4 to 17.3)	11.7 (9.6 to 14.1)
Fatigue:Severe(N=2545, 843)	1.9 (1.4 to 2.5)	1.4 (0.7 to 2.5)
Chills:Any(N=2545, 843)	16 (14.6 to 17.4)	10.3 (8.3 to 12.6)
Chills:Mild(N=2545, 843)	10.6 (9.4 to 11.9)	8.1 (6.3 to 10.1)
Chills:Moderate(N=2545, 843)	4.8 (4 to 5.7)	1.8 (1 to 2.9)
Chills:Severe(N=2545, 843)	0.6 (0.3 to 1)	0.5 (0.1 to 1.2)
Muscle pain:Any(N=2545, 843)	17.8 (16.3 to 19.3)	10.3 (8.3 to 12.6)
Muscle pain:Mild(N=2545, 843)	8.7 (7.6 to 9.8)	5.2 (3.8 to 6.9)
Muscle pain:Moderate(N=2545, 843)	7.9 (6.8 to 9)	4.5 (3.2 to 6.1)
Muscle pain:Severe(N=2545, 843)	1.2 (0.8 to 1.7)	0.6 (0.2 to 1.4)
Joint pain:Any(N=2545, 843)	16.7 (15.3 to 18.2)	9.1 (7.3 to 11.3)
Joint pain:Mild(N=2545, 843)	8.4 (7.4 to 9.6)	5 (3.6 to 6.7)
Joint pain:Moderate(N=2545, 843)	7.5 (6.5 to 8.6)	3.4 (2.3 to 4.9)
Joint pain:Severe(N=2545, 843)	0.8 (0.5 to 1.2)	0.7 (0.3 to 1.5)
Antipyretic medication(N=2545, 843)	13.6 (12.3 to 15)	8.9 (7.1 to 11)

Notes
[17] - Number of subjects analyzed signifies subjects with known values after second vaccination.
[18] - Number of subjects analyzed signifies subjects with known values after second vaccination.

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Third Vaccination

Top of page

End point title

Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Third Vaccination ^[19]

End point description

End point type

Primary

End point timeframe

Within 7 days after third vaccination

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2421 ^[20]	821 ^[21]
Units: percentage of subjects
number (confidence interval 95%)
Fever >=38 degrees C(N=2414, 819)	2.7 (2.1 to 3.4)	2.3 (1.4 to 3.6)
Fever 38 to <38.5degreesC(N=2414, 819)	1.8 (1.3 to 2.4)	1.3 (0.7 to 2.4)
Fever 38.5 to<39 degrees C(N=2414, 819)	0.6 (0.3 to 1)	0.4 (0.1 to 1.1)
Fever 39 to 40 degrees C(N=2414, 819)	0.3 (0.1 to 0.6)	0.5 (0.1 to 1.2)
Fever >40 degrees C(N=2414, 819)	0 (0 to 0.2)	0.1 (0 to 0.7)
Vomiting:Any(N=2421, 821)	1.7 (1.3 to 2.3)	2.2 (1.3 to 3.4)
Vomiting:Mild(N=2421, 821)	1.4 (1 to 2)	1.7 (0.9 to 2.8)
Vomiting:Moderate(N=2421, 821)	0.3 (0.1 to 0.6)	0.5 (0.1 to 1.2)
Vomiting:Severe(N=2421, 821)	0 (0 to 0.2)	0 (0 to 0.4)
Diarrhea:Any(N=2421, 821)	7.7 (6.7 to 8.9)	7.6 (5.8 to 9.6)
Diarrhea:Mild(N=2421, 821)	6.4 (5.5 to 7.5)	6.2 (4.7 to 8.1)
Diarrhea:Moderate(N=2421, 821)	1 (0.6 to 1.5)	1.1 (0.5 to 2.1)
Diarrhea:Severe(N=2421, 821)	0.3 (0.1 to 0.6)	0.2 (0 to 0.9)
Headache:Any(N=2421, 821)	35.4 (33.5 to 37.4)	24.8 (21.9 to 28)
Headache:Mild(N=2421, 821)	18.9 (17.3 to 20.5)	13.5 (11.3 to 16.1)
Headache:Moderate(N=2421, 821)	15.2 (13.8 to 16.7)	10.4 (8.4 to 12.6)
Headache:Severe(N=2421, 821)	1.3 (0.9 to 1.9)	1 (0.4 to 1.9)
Fatigue:Any(N=2421, 821)	35.9 (34 to 37.9)	24.4 (21.5 to 27.4)
Fatigue:Mild(N=2421, 821)	18.4 (16.9 to 20)	13.5 (11.3 to 16.1)
Fatigue:Moderate(N=2421, 821)	15.2 (13.8 to 16.7)	10 (8 to 12.2)
Fatigue:Severe(N=2421, 821)	2.3 (1.8 to 3)	0.9 (0.3 to 1.7)
Chills:Any(N=2421, 821)	13.1 (11.7 to 14.5)	8.3 (6.5 to 10.4)
Chills:Mild(N=2421, 821)	8.7 (7.6 to 9.9)	6.5 (4.9 to 8.4)
Chills:Moderate(N=2421, 821)	3.8 (3.1 to 4.7)	1.7 (0.9 to 2.8)
Chills:Severe(N=2421, 821)	0.5 (0.3 to 0.9)	0.1 (0 to 0.7)
Muscle pain:Any(N=2421, 821)	17.6 (16.1 to 19.1)	11.1 (9 to 13.4)
Muscle pain:Mild(N=2421, 821)	9.5 (8.4 to 10.8)	6.6 (5 to 8.5)
Muscle pain:Moderate(N=2421, 821)	7.2 (6.2 to 8.3)	4.3 (3 to 5.9)
Muscle pain:Severe(N=2421, 821)	0.8 (0.5 to 1.3)	0.2 (0 to 0.9)
Joint pain:Any(N=2421, 821)	16 (14.6 to 17.5)	8.9 (7 to 11.1)
Joint pain:Mild(N=2421, 821)	8.9 (7.8 to 10.1)	5.5 (4 to 7.3)
Joint pain:Moderate(N=2421, 821)	5.9 (5 to 6.9)	3 (2 to 4.5)
Joint pain:Severe(N=2421, 821)	1.2 (0.8 to 1.8)	0.4 (0.1 to 1.1)
Antipyretic medication(N=2421, 821)	12.7 (11.4 to 14.1)	6.8 (5.2 to 8.8)

Notes
[20] - Number of subjects analyzed signifies subjects with known values after third vaccination.
[21] - Number of subjects analyzed signifies subjects with known values after third vaccination.

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After First Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After First Vaccination ^[22]

End point description

End point type

Primary

End point timeframe

Within 30 days after first vaccination

Notes
[22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	0.26 (0.1 to 0.5)	0.33 (0.1 to 1)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Second Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Second Vaccination ^[23]

End point description

End point type

Primary

End point timeframe

Within 30 days after second vaccination

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2570	860
Units: percentage of subjects
number (confidence interval 95%)	0.23 (0.1 to 0.5)	0.23 (0 to 0.8)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Third Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Third Vaccination ^[24]

End point description

Safety population for third vaccination included all subjects who received the third dose of investigational product (rLP2086 or HAV) and for whom safety information was available from third vaccination until post third-vaccination blood draw.

End point type

Primary

End point timeframe

Within 30 days after third vaccination

Notes
[24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2462	835
Units: percentage of subjects
number (confidence interval 95%)	0.32 (0.1 to 0.6)	0.36 (0.1 to 1)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After any Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After any Vaccination ^[25]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

Within 30 days after any vaccination

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	0.78 (0.5 to 1.2)	0.89 (0.4 to 1.7)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase

Top of page

End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase ^[26]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/s aline) and had safety data available.

End point type

Primary

End point timeframe

From the first vaccination up to 1 month after the third vaccination

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	1.49 (1.1 to 2)	1.9 (1.1 to 3)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Follow-up Phase

Top of page

End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Follow-up Phase ^[27]

End point description

Safety population: all subjects who had at least 1 dose investigational product (rLP2086 or HAV/saline) for whom safety information was available from after post third-vaccination blood draw to 6 months after last study vaccination.

End point type

Primary

End point timeframe

From 1 month after third vaccination up to 6 months after the third vaccination

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2524	839
Units: percentage of subjects
number (confidence interval 95%)	0.44 (0.2 to 0.8)	0.6 (0.2 to 1.4)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Throughout the Study Period

Top of page

End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Throughout the Study Period ^[28]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

From the first vaccination up to 6 month after the third vaccination

Notes
[28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	1.89 (1.4 to 2.5)	2.45 (1.5 to 3.7)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After First Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After First Vaccination ^[29]

End point description

End point type

Primary

End point timeframe

Within 30 days after first vaccination

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	5.27 (4.5 to 6.2)	6.69 (5.1 to 8.5)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Second Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Second Vaccination ^[30]

End point description

End point type

Primary

End point timeframe

Within 30 days after second vaccination

Notes
[30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2570	860
Units: percentage of subjects
number (confidence interval 95%)	5.91 (5 to 6.9)	6.51 (5 to 8.4)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Third Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Third Vaccination ^[31]

End point description

End point type

Primary

End point timeframe

Within 30 days after third vaccination

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2462	835
Units: percentage of subjects
number (confidence interval 95%)	5.81 (4.9 to 6.8)	7.43 (5.7 to 9.4)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After any Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After any Vaccination ^[32]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

Within 30 days after any vaccination

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	14.18 (12.9 to 15.6)	16.61 (14.2 to 19.2)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Medically Attended AE During the Vaccination Phase

Top of page

End point title

Percentage of Subjects With at Least 1 Medically Attended AE During the Vaccination Phase ^[33]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

From the first vaccination up to 1 month after the third vaccination

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	25.29 (23.7 to 27)	27.87 (25 to 30.9)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Medically Attended AE During the Follow-Up Phase

Top of page

End point title

Percentage of Subjects With at Least 1 Medically Attended AE During the Follow-Up Phase ^[34]

End point description

Safety population: all subjects who had at least 1 dose of investigational product (rLP2086 or HAV/saline) for whom safety information was available from after post-vaccination 3 blood draw to 6 months after last study vaccination.

End point type

Primary

End point timeframe

From 1 month after third vaccination up to 6 months after the third vaccination

Notes
[34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2524	839
Units: percentage of subjects
number (confidence interval 95%)	15.61 (14.2 to 17.1)	16.92 (14.4 to 19.6)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Throughout the Study Period

Top of page

End point title

Percentage of Subjects With at Least 1 Medically Attended AE Throughout the Study Period ^[35]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

From the first vaccination up to 6 month after the third vaccination

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	32.38 (30.6 to 34.2)	35.56 (32.4 to 38.8)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After First Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After First Vaccination ^[36]

End point description

End point type

Primary

End point timeframe

Within 30 days after first vaccination

Notes
[36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	0 (0 to 0.1)	0.11 (0 to 0.6)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Second Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Second Vaccination ^[37]

End point description

End point type

Primary

End point timeframe

30 days after second vaccination

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2570	860
Units: percentage of subjects
number (confidence interval 95%)	0.08 (0 to 0.3)	0.12 (0 to 0.6)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Third Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Third Vaccination ^[38]

End point description

Safety population for third vaccination included all subjects who received the third dose of investigational product(rLP2086 or HAV)and for whom safety information was available from third vaccination until post third-vaccination blood draw.

End point type

Primary

End point timeframe

Within 30 days after third vaccination

Notes
[38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2462	835
Units: percentage of subjects
number (confidence interval 95%)	0.12 (0 to 0.4)	0 (0 to 0.4)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After any Vaccination

Top of page

End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After any Vaccination ^[39]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

Within 30 Days After any Vaccination

Notes
[39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	0.19 (0.1 to 0.4)	0.22 (0 to 0.8)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase

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End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase ^[40]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

From the first vaccination up to 1 month after the third vaccination

Notes
[40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	0.37 (0.2 to 0.7)	0.56 (0.2 to 1.3)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-Up Phase

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End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-Up Phase ^[41]

End point description

Safety population: all subjects who had at least 1 dose of investigational product (rLP2086 or HAV/saline) for whom safety information was available from after post third-vaccination blood draw to 6 months after last study vaccination.

End point type

Primary

End point timeframe

From 1 month after third vaccination up to 6 months after the third vaccination

Notes
[41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2524	839
Units: percentage of subjects
number (confidence interval 95%)	0.2 (0.1 to 0.5)	0.6 (0.2 to 1.4)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study Period

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End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study Period ^[42]

End point description

Safety population included all subjects who received at least 1 dose of the investigational product and had safety information available.

End point type

Primary

End point timeframe

From the first vaccination up to 6 month after the third vaccination

Notes
[42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	0.56 (0.3 to 0.9)	1.11 (0.5 to 2)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) WIthin 30 Days After First Vaccination

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End point title

Percentage of Subjects With at Least 1 Adverse Event (AE) WIthin 30 Days After First Vaccination ^[43]

End point description

End point type

Primary

End point timeframe

Within 30 days after first vaccination

Notes
[43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	9.51 (8.4 to 10.7)	10.7 (8.8 to 12.9)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Second Vaccination

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End point title

Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Second Vaccination ^[44]

End point description

Safety population for second vaccination included all subjects who received the second dose of investigational product (rLP2086 or HAV) and for whom safety information was available from second vaccination until prior to third vaccination.

End point type

Primary

End point timeframe

Within 30 days after second vaccination

Notes
[44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2570	860
Units: percentage of subjects
number (confidence interval 95%)	11.48 (10.3 to 12.8)	12.67 (10.5 to 15.1)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Third Vaccination

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End point title

Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Third Vaccination ^[45]

End point description

End point type

Primary

End point timeframe

Within 30 days after third vaccination

Notes
[45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2462	835
Units: percentage of subjects
number (confidence interval 95%)	9.91 (8.8 to 11.2)	10.78 (8.8 to 13.1)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Adverse Event Within 30 Days After any Vaccination

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End point title

Percentage of Subjects With at Least 1 Adverse Event Within 30 Days After any Vaccination ^[46]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

Within 30 Days after any vaccination

Notes
[46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	25.32 (23.7 to 27)	26.76 (23.9 to 29.8)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Adverse Event During the Vaccination Phase

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End point title

Percentage of Subjects With at Least 1 Adverse Event During the Vaccination Phase ^[47]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

End point type

Primary

End point timeframe

From the first vaccination up to 1 month after the third vaccination

Notes
[47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	40.74 (38.9 to 42.6)	43.7 (40.4 to 47)

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting at Least 1 Immediate AE After First Vaccination

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End point title

Percentage of Subjects Reporting at Least 1 Immediate AE After First Vaccination ^[48]

End point description

End point type

Primary

End point timeframe

Within 30 minutes after first vaccination

Notes
[48] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2693	897
Units: percentage of subjects
number (confidence interval 95%)	0.1 (0 to 0.4)	0.2 (0 to 0.8)

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting at Least 1 Immediate AE After Second Vaccination

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End point title

Percentage of Subjects Reporting at Least 1 Immediate AE After Second Vaccination ^[49]

End point description

End point type

Primary

End point timeframe

Within 30 minutes after second vaccination

Notes
[49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2570	860
Units: percentage of subjects
number (confidence interval 95%)	0.2 (0 to 0.4)	0.1 (0 to 0.6)

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting at Least 1 Immediate AE After Third Vaccination

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End point title

Percentage of Subjects Reporting at Least 1 Immediate AE After Third Vaccination ^[50]

End point description

End point type

Primary

End point timeframe

Within 30 minutes after third vaccination

Notes
[50] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	2462	835
Units: percentage of subjects
number (confidence interval 95%)	0.1 (0 to 0.3)	0 (0 to 0.4)

No statistical analyses for this end point

Primary: Number of Days Subjects Missed School or Work due to AE During the Vaccination Phase

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End point title

Number of Days Subjects Missed School or Work due to AE During the Vaccination Phase ^[51]

End point description

Safety population included all the subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/s aline) and had safety data available.

End point type

Primary

End point timeframe

From the first vaccination up to 1 month after the third vaccination

Notes
[51] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	rLP2086 (Lots 1-3)	Group 4 HAV/Saline
Number of subjects analysed	539	195
Units: days
arithmetic mean (standard deviation)	3.9 ± 6.56	4 ± 5.19

No statistical analyses for this end point

Secondary: Percentage of Subjects With hSBA Titers >=LLOQ for 10 Secondary Strains Before First Vaccination and 1 Month After Third Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects With hSBA Titers >=LLOQ for 10 Secondary Strains Before First Vaccination and 1 Month After Third Bivalent rLP2086 Vaccination ^[52]

End point description

Evaluable immunogenicity population. Here, N signifies subjects with valid and determinate hSBA titers for the given strain at the specified time point.

End point type

Secondary

End point timeframe

Before first vaccination, 1 month after third vaccination

Notes
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1
Number of subjects analysed	300 ^[53]
Units: percentage of subjects
number (confidence interval 95%)
PMB3175[A29]:Before Vaccination1(N= 269)	17.5 (13.1 to 22.5)
PMB3175[A29]:1Month after Vaccination3(N= 278)	98.6 (96.4 to 99.6)
PMB3010[A06]:Before Vaccination1(N= 277)	9.4 (6.2 to 13.5)
PMB3010[A06]:1Month after Vaccination3(N= 280)	95.7 (92.6 to 97.8)
PMB3040[A07]:Before Vaccination1(N= 269)	43.1 (37.1 to 49.3)
PMB3040[A07]:1Month after Vaccination3(N= 280)	96.4 (93.5 to 98.3)
PMB824[A12]:Before Vaccination1(N= 280)	3.9 (2 to 6.9)
PMB824[A12]:1Month after Vaccination3(N= 277)	75.1 (69.6 to 80.1)
PMB1672[A15]:Before Vaccination1(N= 270)	20.7 (16.1 to 26.1)
PMB1672[A15]:1Month after Vaccination3(N= 266)	87.2 (82.6 to 91)
PMB1989[A19]:Before Vaccination1(N= 274)	11.3 (7.8 to 15.7)
PMB1989[A19]:1Month after Vaccination3(N= 275)	92.7 (89 to 95.5)
PMB1256[B03]:Before Vaccination1 (N= 280)	4.3 (2.2 to 7.4)
PMB1256[B03]:1Month after Vaccination3(N= 279)	92.5 (88.7 to 95.3)
PMB866[B09]:Before Vaccination1(N= 277)	15.2 (11.2 to 19.9)
PMB866[B09]:1Month after Vaccination3(N= 276)	86.2 (81.6 to 90.1)
PMB431[B15]:Before Vaccination1(N= 275)	28.7 (23.5 to 34.5)
PMB431[B15]:1Month after Vaccination3(N= 281)	98.2 (95.9 to 99.4)
PMB648[B16]:Before Vaccination1(N= 276)	7.6 (4.8 to 11.4)
PMB648[B16]:1Month after Vaccination3(N= 278)	81.7 (76.6 to 86)

Notes
[53] - Number of subjects analyzed signifies subjects with valid, determinate hSBA titers for given strain

No statistical analyses for this end point

Secondary: Percentage of Subjects With hSBA Titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64, >=1:128 for Each of the 10 Secondary Strains, Before Vaccination 1 and 1 Month After the Third Bivalent rLP2086 Vaccination

Top of page

End point title

Percentage of Subjects With hSBA Titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64, >=1:128 for Each of the 10 Secondary Strains, Before Vaccination 1 and 1 Month After the Third Bivalent rLP2086 Vaccination ^[54]

End point description

Evaluable immunogenicity population. Here, N signifies subjects with valid and determinate hSBA titers for the given strain at the specified time point.

End point type

Secondary

End point timeframe

Before first vaccination, 1 month after third vaccination (Vac)

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1
Number of subjects analysed	300 ^[55]
Units: percentage of subjects
number (confidence interval 95%)
Before Vaccination1:PMB3175[A29]1:4(N=269)	19 (14.5 to 24.2)
1 month after Vac3:PMB3175[A29]1:4(N=278)	98.6 (96.4 to 99.6)
Before Vaccination1:PMB3175[A29]1:8(N=269)	17.5 (13.1 to 22.5)
1 month after Vac3:PMB3175[A29]1:8(N=278)	98.6 (96.4 to 99.6)
Before Vaccination 1:PMB3175[A29]1:16(N=269)	16.7 (12.5 to 21.7)
1 month after Vac3:PMB3175[A29]1:16(N=278)	98.6 (96.4 to 99.6)
Before Vaccination1:PMB3175[A29]1:32(N=269)	10.8 (7.3 to 15.1)
1 month after Vac3:PMB3175[A29]1:32(N=278)	97.5 (94.9 to 99)
Before Vaccination 1:PMB3175[A29]1:64(N=269)	4.8 (2.6 to 8.1)
1 month after Vac3:PMB3175[A29]1:64(N=278)	86 (81.3 to 89.8)
Before Vaccination 1:PMB3175[A29]1:128(N=269)	1.1 (0.2 to 3.2)
1 month after Vac3:PMB3175[A29]1:128(N=278)	52.2 (46.1 to 58.2)
Before Vaccination 1:PMB3010[A06]1:4(N=277)	9.7 (6.5 to 13.9)
1 month after Vac3:PMB3010[A06]1:4(N=280)	96.1 (93.1 to 98)
Before Vaccination 1:PMB3010[A06]1:8(N=277)	9.7 (6.5 to 13.9)
1 month after Vac3:PMB3010[A06]1:8(N=280)	96.1 (93.1 to 98)
Before Vaccination 1:PMB3010[A06]1:16(N=277)	9.4 (6.2 to 13.5)
1 month after Vac3:PMB3010[A06]1:16(N=280)	95.7 (92.6 to 97.8)
Before Vaccination 1:PMB3010[A06]1:32(N=277)	6.1 (3.6 to 9.6)
1 month after Vac3:PMB3010[A06]1:32(N=280)	93.6 (90 to 96.1)
Before Vaccination1: PMB3010[A06]1:64(N=277)	2.9 (1.3 to 5.6)
1 month after Vac3:PMB3010[A06]1:64(N=280)	78.2 (72.9 to 82.9)
Before Vaccination1:PMB3010[A06]1:128(N=277)	1.4 (0.4 to 3.7)
1 month after Vac3:PMB3010[A06]1:128(N=280)	44.3 (38.4 to 50.3)
Before Vaccination1:PMB3040[A07]1:4(N=269)	43.1 (37.1 to 49.3)
1 month after Vac3:PMB3040[A07]1:4(N=280)	96.4 (93.5 to 98.3)
Before Vaccination1:PMB3040[A07]1:8(N=269)	43.1 (37.1 to 49.3)
1 month after Vac3:PMB3040[A07]1:8(N=280)	96.4 (93.5 to 98.3)
Before Vaccination1:PMB3040[A07]1:16(N=269)	42.8 (36.8 to 48.9)
1 month after Vac3:PMB3040[A07]1:16(N=280)	96.4 (93.5 to 98.3)
Before Vaccination1:PMB3040[A07]1:32(N=269)	37.2 (31.4 to 43.3)
1 month after Vac3:PMB3040[A07]1:32(N=280)	93.6 (90 to 96.1)
Before Vaccination1:PMB3040[A07]1:64(N=269)	21.6 (16.8 to 27)
1 month after Vac3:PMB3040[A07]1:64(N=280)	78.2 (72.9 to 82.9)
Before Vaccination1:PMB3040[A07]1:128(N=269)	5.6 (3.2 to 9)
1 month after Vac3:PMB3040[A07]1:128(N=280)	30.4 (25 to 36.1)
Before Vaccination1:PMB824[A12]1:4(N=280)	5.4 (3 to 8.7)
1 month after Vac3:PMB824[A12]1:4(N=277)	77.6 (72.2 to 82.4)
Before Vaccination1:PMB824[A12]1:8(N=280)	4.6 (2.5 to 7.8)
1 month after Vac3:PMB824[A12]1:8(N=277)	77.3 (71.9 to 82.1)
Before Vaccination1:PMB824[A12]1:16(N=280)	3.9 (2 to 6.9)
1 month after Vac3:PMB824[A12]1:16(N=277)	75.1 (69.6 to 80.1)
Before Vaccination1:PMB824[A12]1:32(N=280)	2.5 (1 to 5.1)
1 month after Vac3:PMB824[A12]1:32(N=277)	51.3 (45.2 to 57.3)
Before Vaccination1:PMB824[A12]1:64(N=280)	0 (0 to 1.3)
1 month after Vac3:PMB824[A12]1:64(N=277)	19.5 (15 to 24.7)
Before Vaccination1:PMB824[A12]1:128(N=280)	0 (0 to 1.3)
1 month after Vac3:PMB824[A12]1:128(N=277)	1.8 (0.6 to 4.2)
Before Vaccination1:PMB1672[A15]1:4(N=270)	22.6 (17.7 to 28.1)
1 month after Vac3:PMB1672[A15]1:4(N=266)	87.2 (82.6 to 91)
Before Vaccination1:PMB1672[A15]1:8(N=270)	20.7 (16.1 to 26.1)
1 month after Vac3:PMB1672[A15]1:8(N=266)	87.2 (82.6 to 91)
Before Vaccination1:PMB1672[A15]1:16(N=270)	17 (12.8 to 22.1)
1 month after Vac3:PMB1672[A15]1:16(N=266)	85 (80.1 to 89)
Before Vaccination1:PMB1672[A15]1:32(N=270)	13.3 (9.5 to 18)
1 month after Vac3:PMB1672[A15]1:32(N=266)	71.4 (65.6 to 76.8)
Before Vaccination1:PMB1672[A15]1:64(N=270)	3.7 (1.8 to 6.7)
1 month after Vac3:PMB1672[A15] 1:64(N=266)	40.2 (34.3 to 46.4)
Before Vaccination1:PMB1672[A15]1:128(N=270)	0.4 (0 to 2)
1 month after Vac3:PMB1672[A15]1:128(N=266)	10.5 (7.1 to 14.9)
Before Vaccination1:PMB1989[A19]1:4(N=274)	20.8 (16.2 to 26.1)
1 month after Vac3:PMB1989[A19]1:4(N=275)	93.8 (90.3 to 96.4)
Before Vaccination1:PMB1989[A19]1:8(N=274)	18.6 (14.2 to 23.7)
1 month after Vac3:PMB1989[A19]1:8(N=275)	93.8 (90.3 to 96.4)
Before Vaccination1:PMB1989[A19]1:16(N=274)	11.3 (7.8 to 15.7)
1 month after Vac3:PMB1989[A19]1:16(N=275)	92.7 (89 to 95.5)
Before Vaccination1:PMB1989[A19]1:32(N=274)	5.8 (3.4 to 9.3)
1 month after Vac3:PMB1989[A19]1:32(N=275)	85.5 (80.7 to 89.4)
Before Vaccination1:PMB1989[A19]1:64(N=274)	1.8 (0.6 to 4.2)
1 month after Vac3:PMB1989[A19]1:64(N=275)	60 (53.9 to 65.8)
Before Vaccination1:PMB1989[A19]1:128(N=274)	0.4 (0 to 2)
1 month after Vac3:PMB1989[A19]1:128(N=275)	33.1 (27.6 to 39)
Before Vaccination1:PMB1256[B03]1:4(N=280)	5 (2.8 to 8.2)
1 month after Vac3:PMB1256[B03] 1:4(N=279)	92.5 (88.7 to 95.3)
Before Vaccination 1:PMB1256[B03] 1:8(N=280)	4.3 (2.2 to 7.4)
1 month after Vac3:PMB1256[B03] 1:8(N=279)	92.5 (88.7 to 95.3)
Before Vaccination 1:PMB1256[B03] 1:16(N=280)	4.3 (2.2 to 7.4)
1 month after Vac3:PMB1256[B03] 1:16(N=279)	92.1 (88.3 to 95)
Before Vaccination 1:PMB1256[B03] 1:32(N=280)	3.9 (2 to 6.9)
1 month after Vac3:PMB1256[B03] 1:32(N=279)	81.4 (76.3 to 85.8)
Before Vaccination 1:PMB1256[B03] 1:64(N=280)	2.9 (1.2 to 5.6)
1 month after Vac3:PMB1256[B03] 1:64(N=279)	60.6 (54.6 to 66.3)
Before Vaccination 1:PMB1256[B03] 1:128(N=280)	0.4 (0 to 2)
1 month after Vac3:PMB1256[B03] 1:128(N=279)	29.4 (24.1 to 35.1)
Before Vaccination 1:PMB866[B09] 1:4(N=277)	15.5 (11.5 to 20.3)
1 month after Vac3:PMB866[B09] 1:4(N=276)	86.6 (82 to 90.4)
Before Vaccination 1:PMB866[B09] 1:8(N=277)	15.2 (11.2 to 19.9)
1 month after Vac3:PMB866[B09] 1:8(N=276)	86.2 (81.6 to 90.1)
Before Vaccination 1:PMB866[B09] 1:16(N=277)	13.7 (9.9 to 18.3)
1 month after Vac3:PMB866[B09] 1:16(N=276)	83.7 (78.8 to 87.9)
Before Vaccination 1:PMB866[B09] 1:32(N=277)	8.7 (5.6 to 12.6)
1 month after Vac3:PMB866[B09] 1:32(N=276)	54 (47.9 to 60)
Before Vaccination 1:PMB866[B09] 1:64(N=277)	0.4 (0 to 2)
1 month after Vac3:PMB866[B09] 1:64(N=276)	21.4 (16.7 to 26.7)
Before Vaccination 1:PMB866[B09] 1:128(N=277)	0 (0 to 1.3)
1 month after Vac3:PMB866[B09] 1:128(N=276)	4.3 (2.3 to 7.5)
Before Vaccination 1:PMB431[B15] 1:4(N=275)	30.5 (25.2 to 36.4)
1 month after Vac3:PMB431[B15] 1:4(N=281)	98.2 (95.9 to 99.4)
Before Vaccination 1:PMB431[B15] 1:8(N=275)	28.7 (23.5 to 34.5)
1 month after Vac3:PMB431[B15] 1:8(N=281)	98.2 (95.9 to 99.4)
Before Vaccination 1:PMB431[B15] 1:16(N=275)	27.6 (22.4 to 33.3)
1 month after Vac3:PMB431[B15] 1:16(N=281)	97.5 (94.9 to 99)
Before Vaccination 1:PMB431[B15] 1:32(N=275)	21.8 (17.1 to 27.2)
1 month after Vac3:PMB431[B15] 1:32(N=281)	85.1 (80.3 to 89)
Before Vaccination 1:PMB431[B15] 1:64(N=275)	8.4 (5.4 to 12.3)
1 month after Vac3:PMB431[B15] 1:64(N=281)	56.2 (50.2 to 62.1)
Before Vaccination 1:PMB431[B15] 1:128(N=275)	0.4 (0 to 2)
1 month after Vac3:PMB431[B15] 1:128(N=281)	19.2 (14.8 to 24.3)
Before Vaccination 1:PMB648[B16] 1:4(N=276)	8.7 (5.7 to 12.7)
1 month after Vac3:PMB648[B16] 1:4(N=278)	82.7 (77.8 to 87)
Before Vaccination 1:PMB648[B16] 1:8(N=276)	7.6 (4.8 to 11.4)
1 month after Vac3:PMB648[B16] 1:8(N=278)	81.7 (76.6 to 86)
Before Vaccination 1:PMB648[B16] 1:16(N=276)	7.6 (4.8 to 11.4)
1 month after Vac3:PMB648[B16] 1:16(N=278)	79.9 (74.7 to 84.4)
Before Vaccination 1:PMB648[B16] 1:32(N=276)	6.2 (3.6 to 9.7)
1 month after Vac3:PMB648[B16] 1:32(N=278)	54 (47.9 to 59.9)
Before Vaccination 1:PMB648[B16] 1:64(N=276)	1.8 (0.6 to 4.2)
1 month after Vac3:PMB648[B16] 1:64(N=278)	24.1 (19.2 to 29.6)
Before Vaccination 1:PMB648[B16] 1:128(N=276)	0.4 (0 to 2)
1 month after Vac3:PMB648[B16] 1:128(N=278)	5.8 (3.3 to 9.2)

Notes
[55] - Number of subjects analyzed signifies subjects with valid, determinate hSBA titers for given strain

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers (GMTs) for Each of the 10 Secondary Strains Before First Vaccination and 1 Month After the Third Bivalent rLP2086 Vaccination

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End point title

hSBA Geometric Mean Titers (GMTs) for Each of the 10 Secondary Strains Before First Vaccination and 1 Month After the Third Bivalent rLP2086 Vaccination ^[56]

End point description

Evaluable immunogenicity population. Here, N signifies subjects with valid and determinate assay results for the given antigen or strain.

End point type

Secondary

End point timeframe

Before first vaccination, 1 month after third vaccination

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1
Number of subjects analysed	300 ^[57]
Units: titer
geometric mean (confidence interval 95%)
PMB3175[A29]:Before Vaccination1(N= 269)	5.7 (5.16 to 6.28)
PMB3175[A29]:1 Month after Vaccination3(N= 278)	93.5 (84.79 to 103.09)
PMB3010[A06]:Before Vaccination1(N= 277)	9.3 (8.68 to 9.91)
PMB3010[A06]:1 Month after Vaccination3(N= 280)	78.6 (70.94 to 87.08)
PMB3040[A07]:Before Vaccination1(N= 269)	11.4 (9.75 to 13.23)
PMB3040[A07]:1 Month after Vaccination3(N= 280)	63.5 (57.93 to 69.66)
PMB824[A12]: Before Vaccination1(N= 280)	8.4 (8.14 to 8.59)
PMB824[A12]:1 Month after Vaccination3(N= 277)	22.3 (20.37 to 24.45)
PMB1672[A15]:Before Vaccination1(N= 270)	5.9 (5.32 to 6.46)
PMB1672[A15]:1 Month after Vaccination3(N= 266)	31 (27.43 to 35.07)
PMB1989[A19]:Before Vaccination1(N= 274)	9.1 (8.7 to 9.62)
PMB1989[A19]:1 Month after Vaccination3(N= 275)	57.6 (51.3 to 64.6)
PMB1256[B03]:Before Vaccination1(N= 280)	4.5 (4.19 to 4.75)
PMB1256[B03]:1 Month after Vaccination3(N= 279)	51.7 (45.36 to 58.89)
PMB866[B09]:Before Vaccination1(N= 277)	5.2 (4.82 to 5.62)
PMB866[B09]:1 Month after Vaccination3(N= 276)	22.9 (20.48 to 25.63)
PMB431[B15]:Before Vaccination1(N= 275)	7.3 (6.49 to 8.23)
PMB431[B15]:1 Month after Vaccination3(N= 281)	47.7 (43.66 to 52.16)
PMB648[B16]:Before Vaccination1(N= 276)	4.7 (4.39 to 5.05)
PMB648[B16]:1 Month after Vaccination3(N= 278)	22.1 (19.6 to 24.98)

Notes
[57] - Number of subjects analyzed signifies subjects with valid, determinate hSBA titers for given strain

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Composite hSBA Titer >=Lower Limit of Quantitation for all 4 Primary Strains Before First Vaccination and 1 Month After Second Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects Achieving Composite hSBA Titer >=Lower Limit of Quantitation for all 4 Primary Strains Before First Vaccination and 1 Month After Second Bivalent rLP2086 Vaccination ^[58]

End point description

Evaluable immunogenicity population. Here, N signifies subjects valid and determinate hSBA results on all 4 strains at the given time point.

End point type

Secondary

End point timeframe

Before vaccination 1, 1 Month after Vaccination 2

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1
Number of subjects analysed	1279
Units: percentage of subjects
number (confidence interval 95%)
Before First Vaccination(N= 1088)	1.1 (0.6 to 1.9)
1 Month after Vaccination2(N= 1122)	54.1 (51.1 to 57)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving at Least a 4-Fold Increase in hSBA Titer for Each of the 4 Primary Strains Before First Vaccination to 1 Month After the Second Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects Achieving at Least a 4-Fold Increase in hSBA Titer for Each of the 4 Primary Strains Before First Vaccination to 1 Month After the Second Bivalent rLP2086 Vaccination ^[59]

End point description

Evaluable immunogenicity population. Here, N signifies subjects with valid and determinate hSBA titers for the given strain at both the specified time point.

End point type

Secondary

End point timeframe

One month after second Bivalent rLP2086 vaccination

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1
Number of subjects analysed	1279
Units: percentage of subjects
number (confidence interval 95%)
PMB80[A22] (N=1223)	73.8 (71.2 to 76.2)
PMB2001[A56] (N=1122)	84.8 (82.5 to 86.8)
PMB2948[B24] (N=1201)	56.2 (53.3 to 59)
PMB2707[B44] (N=1197)	55.9 (53 to 58.7)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving at Least a 4-Fold Increase in hSBA Titer for 2 Primary Strains Before First Vaccination to 1 Month After the Second and Third Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects Achieving at Least a 4-Fold Increase in hSBA Titer for 2 Primary Strains Before First Vaccination to 1 Month After the Second and Third Bivalent rLP2086 Vaccination ^[60]

End point description

Evaluable immunogenicity population. Here, N signifies subjects with valid and determinate hSBA titers for the given strain at both the specified time point.

End point type

Secondary

End point timeframe

One month after second, third vaccination

Notes
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3
Number of subjects analysed	519	493
Units: percentage of subjects
number (confidence interval 95%)
PMB80[A22]:1 Month after Vaccination2(N=493, 473)	71.2 (67 to 75.2)	74.6 (70.5 to 78.5)
PMB80[A22]:1 Month after Vaccination3(N=501, 478)	83.8 (80.3 to 86.9)	86 (82.5 to 89)
PMB2948[B24]:1 Month after Vaccination2(N=490,463)	56.7 (52.2 to 61.2)	56.8 (52.2 to 61.4)
PMB2948[B24]:1 Month after Vaccination3(N=507,472)	76.5 (72.6 to 80.2)	78.4 (74.4 to 82)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers (GMTs) for 4 Primary Test Strains and for 2 Primary Test Strains and Before First Vaccination and 1 Month After the Second Bivalent rLP2086 Vaccination

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End point title

hSBA Geometric Mean Titers (GMTs) for 4 Primary Test Strains and for 2 Primary Test Strains and Before First Vaccination and 1 Month After the Second Bivalent rLP2086 Vaccination ^[61]

End point description

Evaluable immunogenicity population. Here N signifies subjects with valid and determinate hSBA titers for the given strain at the specified timepoint. Here, 99999 signifies geometric mean and -99999 and 99999 CI upper and lower limits for primary strains PMB2001 [A56] and PMB2707 [B44] for the reporting groups 2 and 3 as data was not planned to be analyzed for the former strains.

End point type

Secondary

End point timeframe

Before vaccination (Vac)1, 1 Month after Vac 2

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3
Number of subjects analysed	1279	519	493
Units: titer
geometric mean (confidence interval 95%)
PMB80[A22]:Before Vac 1(N=1238,502,479)	12.6 (12.08 to 13.14)	12.9 (12.06 to 13.79)	12.2 (11.43 to 13.04)
PMB80[A22]:1 Month after Vac 2(N=1263,510,487)	50.4 (47.76 to 53.09)	47.7 (43.82 to 51.97)	49.6 (45.58 to 53.99)
PMB2001[A56]:Before Vac1(N=1135,0,0)	8.4 (7.8 to 9.05)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
PMB2001[A56]:1 Month after Vac2(N=1222,0,0)	131.2 (124.03 to 138.7)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
PMB2948[B24]:Before Vac1(N=1264,510,486)	4.5 (4.37 to 4.6)	4.6 (4.43 to 4.85)	4.6 (4.43 to 4.88)
PMB2948[B24]:1 Month after Vac2(N=1216, 499,470)	14.3 (13.45 to 15.31)	14.5 (13.23 to 15.98)	15.2 (13.75 to 16.85)
PMB2707[B44]:Before Vac1(N=1230,0,0)	4.3 (4.17 to 4.34)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
PMB2707[B44]:1 Month after Vac2(N=1204,0,0)	17.1 (15.8 to 18.6)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

No statistical analyses for this end point

Secondary: Percentage of Subjects With hSBA Titers >=1:4,>=1:8,>=1:16,>=1:32,>=1:64,>=1:128 for Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects With hSBA Titers >=1:4,>=1:8,>=1:16,>=1:32,>=1:64,>=1:128 for Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination ^[62]

End point description

Results for PMB80[A22] 1:16, PMB2001[A56] 1:8, PMB2948[B24] 1:8 and PMB2707[B44] 1:8 are reported under secondary endpoint ‘Percentage of Subjects With hSBA Titers >=LLOQ for 4 Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination. Evaluable immunogenicity population. Here N signifies subjects with valid and determinate hSBA titers for the given strain at the specified time point. Here, 99999 signifies number and -99999 and 99999 CI upper and lower limits for primary strains PMB2001 [A56] and PMB2707 [B44] for the reporting groups 2 and 3 as data was not planned to be analysed for the former strains.

End point type

Secondary

End point timeframe

Before Vaccination (Vac) 1, 1 Month after Vac 2, 3

Notes
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3
Number of subjects analysed	1279	519	493
Units: percentage of subjects
number (confidence interval 95%)
Before Vac1:PMB80[A22]1:4(N=1238,502,479)	36.2 (33.5 to 38.9)	39.6 (35.3 to 44.1)	36.7 (32.4 to 41.2)
1monthafterVac2:PMB80[A22]1:4(N=1263,510,487)	94.9 (93.6 to 96.1)	93.7 (91.3 to 95.7)	95.5 (93.2 to 97.1)
1monthafterVac3:PMB80[A22]1:4(N=1266,518,492)	97.9 (97 to 98.7)	98.1 (96.5 to 99.1)	98.4 (96.8 to 99.3)
Before Vac1:PMB80[A22]1:8(N=1238,502,479)	34.8 (32.2 to 37.5)	39 (34.8 to 43.5)	34.7 (30.4 to 39.1)
1monthafterVac2:PMB80[A22]1:8(N=1263,510,487)	94.7 (93.3 to 95.9)	93.5 (91 to 95.5)	95.5 (93.2 to 97.1)
1monthafterVac3:PMB80[A22]1:8(N=1266,518,492)	97.9 (97 to 98.7)	98.1 (96.5 to 99.1)	98.4 (96.8 to 99.3)
Before Vac1:PMB80[A22]1:32(N=1238,502,479)	20.9 (18.7 to 23.3)	21.7 (18.2 to 25.6)	19.8 (16.4 to 23.7)
1monthafterVac2:PMB80[A22]1:32(N=1263,510,487)	81.9 (79.7 to 84)	79.4 (75.6 to 82.8)	80.7 (76.9 to 84.1)
1monthafterVac3:PMB80[A22]1:32(N=1266,518,492)	93 (91.4 to 94.3)	92.1 (89.4 to 94.3)	93.1 (90.5 to 95.2)
Before Vac1:PMB80[A22]1:64(N=1238,502,479)	8.5 (7 to 10.2)	9.6 (7.1 to 12.5)	5.4 (3.6 to 7.9)
1monthafterVac2:PMB80[A22]1:64(N=1263,510,487)	51.8 (49 to 54.6)	49.6 (45.2 to 54)	51.5 (47 to 56.1)
1monthafterVac3:PMB80[A22]1:64(N=1266,518,492)	75.3 (72.8 to 77.6)	75.5 (71.5 to 79.1)	73.6 (69.4 to 77.4)
Before Vac1:PMB80[A22]1:128(N=1238,502,479)	2 (1.3 to 3)	2 (1 to 3.6)	2.5 (1.3 to 4.3)
1monthafterVac2:PMB80[A22]1:128(N=1263,510,487)	24.5 (22.1 to 26.9)	23.5 (19.9 to 27.5)	24.4 (20.7 to 28.5)
1monthafterVac3:PMB80[A22]1:128(N=1266,518,492)	48.3 (45.6 to 51.1)	46.3 (42 to 50.7)	49.2 (44.7 to 53.7)
Before Vac1:PMB2001[A56]1:4(N=1135,0,0)	29.5 (26.9 to 32.3)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1monthafterVac2:PMB2001[A56]1:4(N=1222,0,0)	99.1 (98.4 to 99.5)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1monthafterVac3:PMB2001[A56]1:4(N=1229,0,0)	99.5 (98.9 to 99.8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac 1: PMB2001[A56]1:16(N=1135,0,0)	27.4 (24.8 to 30.1)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1monthafterVac2:PMB2001[A56]1:16(N=1222,0,0)	99.1 (98.4 to 99.5)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1monthafterVac3:PMB2001[A56]1:16(N=1229,0,0)	99.4 (98.8 to 99.8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac1:PMB2001[A56]1:32(N=1135,0,0)	25.6 (23 to 28.2)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac2: PMB2001[A56]1:32(N=1222,0,0)	97.2 (96.1 to 98.1)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month afterVac3:PMB2001[A56]1:32(N=1229,0,0)	98.6 (97.8 to 99.2)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac 1:PMB2001[A56]1:64(N=1135,0,0)	17.1 (14.9 to 19.4)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month afterVac2: PMB2001[A56]1:64(N=1222,0,0)	89.4 (87.6 to 91.1)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac3: PMB2001[A56]1:64(N=1229,0,0)	94.5 (93 to 95.7)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac 1:PMB2001[A56]1:128(N=1135,0,0)	6.4 (5.1 to 8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac2:PMB2001[A56]1:128(N=1222,0,0)	63.4 (60.6 to 66.1)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month afterVac3:PMB2001[A56]1:128(N=1229,0,0)	82.9 (80.7 to 85)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac1:PMB2948[B24]1:4(N=1264,510,486)	6.8 (5.5 to 8.3)	10.2 (7.7 to 13.2)	9.5 (7 to 12.4)
1monthafterVac2:PMB2948[B24]1:4(N=1216,499,470)	69.2 (66.6 to 71.8)	72.9 (68.8 to 76.8)	74 (69.8 to 78)
1monthafterVac3:PMB2948[B24]1:4(N=1250,516,479)	88.9 (87 to 90.6)	89.9 (87 to 92.4)	91.6 (88.8 to 94)
Before Vac1:PMB2948[B24]1:16(N=1264,510,486)	5.4 (4.2 to 6.8)	7.5 (5.3 to 10.1)	7 (4.9 to 9.6)
1monthafterVac2:PMB2948[B24]1:16(N=1216,499,470)	60 (57.2 to 62.8)	61.5 (57.1 to 65.8)	62.1 (57.6 to 66.5)
1monthafterVac3:PMB2948[B24]1:16(N=1250,516,479)	82.6 (80.4 to 84.7)	81.2 (77.6 to 84.5)	83.1 (79.4 to 86.3)
Before Vac1:PMB2948[B24]1:32(N=1264,510,486)	2.8 (2 to 3.9)	3.9 (2.4 to 6)	3.7 (2.2 to 5.8)
1monthafterVac2:PMB2948[B24]1:32(N=1216,499,470)	33 (30.3 to 35.7)	34.5 (30.3 to 38.8)	35.5 (31.2 to 40)
1monthafterVac3:PMB2948[B24]1:32(N=1250,516,479)	52.1 (49.3 to 54.9)	54.8 (50.4 to 59.2)	54.1 (49.5 to 58.6)
Before Vac1:PMB2948[B24]1:64(N=1264,510,486)	1.3 (0.7 to 2)	1.2 (0.4 to 2.5)	1.9 (0.9 to 3.5)
1monthafterVac2:PMB2948[B24]1:64(N=1216,499,470)	15.3 (13.3 to 17.4)	13 (10.2 to 16.3)	15.3 (12.2 to 18.9)
1monthafterVac3:PMB2948[B24]1:64(N=1250,516,479)	22.8 (20.5 to 25.2)	27.5 (23.7 to 31.6)	25.3 (21.4 to 29.4)
Before Vac1:PMB2948[B24]1:128(N=1264,510,486)	0.5 (0.2 to 1)	0.2 (0 to 1.1)	0.4 (0 to 1.5)
1monthafterVac2:PMB2948[B24]1:128(N=1216,499,470)	6.2 (4.9 to 7.7)	5.2 (3.4 to 7.5)	7 (4.9 to 9.7)
1monthafterVac3:PMB2948[B24]1:128(N=1250,516,479)	8.9 (7.4 to 10.6)	11.2 (8.6 to 14.3)	8.6 (6.2 to 11.4)
Before Vac1:PMB2707[B44]1:4(N=1230,0,0)	4.6 (3.5 to 5.9)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1month after Vac2:PMB2707[B44]1:4(N=1204,0,0)	66.7 (64 to 69.4)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1month after Vac3:PMB2707[B44]1:4(N=1210.0,0)	90.4 (88.6 to 92)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac1:PMB2707[B44]1:16(N=1230,0,0)	3 (2.1 to 4.1)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac2: PMB2707[B44]1:16(N=1204,0,0)	57.7 (54.9 to 60.5)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac3:PMB2707[B44]1:16(N=1210,0,0)	86.8 (84.7 to 88.6)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac 1:PMB2707[B44]1:32(N=1230,0,0)	1.6 (1 to 2.5)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac2:PMB2707[B44]1:32(N=1204,0,0)	39 (36.3 to 41.9)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac3: PMB2707[B44]1:32(N=1210,0,0)	71.6 (68.9 to 74.1)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac 1:PMB2707[B44]1:64(N=1230,0,0)	0.7 (0.3 to 1.3)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac2:PMB2707[B44]1:64(N=1204,0,0)	23.3 (21 to 25.8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac3:PMB2707[B44]1:64(N=1210,0,0)	54.5 (51.7 to 57.4)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac 1:PMB2707[B44]1:128(N=1230,0,0)	0.2 (0 to 0.6)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac2:PMB2707[B44]1:128(N=1204,0,0)	13 (11.2 to 15.1)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac3:PMB2707[B44]1:128(N=1210,0,0)	35 (32.4 to 37.8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving at Least a 3-Fold Increase in hSBA Titer for 4 Primary Test Strains and for Primary Test Starins Before First Vaccination to 1 Month After Third Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects Achieving at Least a 3-Fold Increase in hSBA Titer for 4 Primary Test Strains and for Primary Test Starins Before First Vaccination to 1 Month After Third Bivalent rLP2086 Vaccination ^[63]

End point description

Data was not reported because 3-fold rise analyses was not performed as per change in planned analysis.

End point type

Secondary

End point timeframe

One month after third bivalent rLP2086 vaccination

Notes
[63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3
Number of subjects analysed	0 ^[64]	0 ^[65]	0 ^[66]
Units: percentage of subjects
number (confidence interval 95%)	( to )	( to )	( to )

Notes
[64] - 3-Fold rise analyses was not performed as per change in planned analysis.
[65] - 3-Fold rise analyses was not performed as per change in planned analysis.
[66] - 3-Fold rise analyses was not performed as per change in planned analysis.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving at Least a 2-Fold Increase in hSBA Titer for 4 Primary Test Strains and for 2 Primary Test Starins Before First Vaccination to 1 Month After the Third Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects Achieving at Least a 2-Fold Increase in hSBA Titer for 4 Primary Test Strains and for 2 Primary Test Starins Before First Vaccination to 1 Month After the Third Bivalent rLP2086 Vaccination ^[67]

End point description

Evaluable immunogenicity population. Here N signifies subjects with valid and determinate hSBA titers for the given strain at the specified timepoint. Here, 99999 signifies number and -99999 and 99999 CI upper and lower limits for primary strains PMB2001 [A56] and PMB2707 [B44] for the reporting groups 2 and 3 as data was not planned to be analysed for the former strains.

End point type

Secondary

End point timeframe

One month after third bivalent rLP2086 vaccination (Vac)

Notes
[67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3
Number of subjects analysed	1279	519	493
Units: percentage of subjects
number (confidence interval 95%)
PMB80[A22]:1 Month after Vac 3(N=1225,501,478)	91.43 (89.7 to 92.9)	92.02 (89.3 to 94.2)	93.51 (90.9 to 95.6)
PMB2001[A56]:1 Month after Vac 3(N=1128,0,0)	95.04 (93.6 to 96.2)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
PMB2948[B24]:1 Month after Vac 3(N=1235,507,472)	81.05 (78.8 to 83.2)	79.09 (75.3 to 82.6)	80.93 (77.1 to 84.4)
PMB2707[B44]:1 Month after Vac 3(N=1203,0,0)	86.62 (84.6 to 88.5)	99999 (-99999 to 99999)	-99999 (-99999 to 99999)

No statistical analyses for this end point

Secondary: Percentage of Subjects With hSBA Titers >=LLOQ for 4 Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination

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End point title

Percentage of Subjects With hSBA Titers >=LLOQ for 4 Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination ^[68]

End point description

Evaluable immunogenicity population. Here N signifies subjects with valid and determinate hSBA titers for the given strain at the specified time point. Here, 99999 signifies number and -99999 and 99999 CI upper and lower limits for primary strains PMB2001 [A56] and PMB2707 [B44] for the reporting groups 2 and 3 as data was not planned to be analysed for the former strains.

End point type

Secondary

End point timeframe

Before Vaccination (Vac) 1, 1 Month after Vac 2, 3

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Group 1 rLP2086 Lot 1	Group 2 rLP2086 Lot 2	Group 3 rLP2086 Lot 3
Number of subjects analysed	1279	519	493
Units: percentage of subjects
number (confidence interval 95%)
Before Vac 1: PMB80[A22] 1:16(N=1238, 502, 479)	33.2 (30.6 to 35.9)	34.9 (30.7 to 39.2)	31.7 (27.6 to 36.1)
1month after Vac2:PMB80[A22] 1:16(N=1263,510,487)	94.3 (92.9 to 95.5)	92.7 (90.1 to 94.8)	94.7 (92.3 to 96.5)
1month after Vac3:PMB80[A22]1:16(N=1266,518,492)	97.8 (96.8 to 98.5)	97.3 (95.5 to 98.5)	98.2 (96.6 to 99.2)
Before Vac 1: PMB2001[A56] 1:8(N=1135,0,0)	27.5 (24.9 to 30.2)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac2:PMB2001[A56]1:8(N=1222,0,0)	99.1 (98.4 to 99.5)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1 month after Vac3:PMB2001[A56]1:8(N=1229,0,0)	99.5 (98.9 to 99.8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
Before Vac 1: PMB2948[B24]1:8(N=1264,510,486)	6.4 (5.1 to 7.9)	8.6 (6.3 to 11.4)	8.4 (6.1 to 11.3)
1month after Vac2:PMB2948[B24]1:8(N=1216,499,470)	66.4 (63.6 to 69)	70.1 (65.9 to 74.1)	70.2 (65.9 to 74.3)
1month after Vac3:PMB2948[B24]1:8(N=1250,516,479)	87.1 (85.1 to 88.9)	87.6 (84.4 to 90.3)	90 (86.9 to 92.5)
Before Vac 1: PMB2707[B44]1:8(N=1230,0,0)	3.6 (2.6 to 4.8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1month after Vac2: PMB2707[B44]1:8(N=1204,0,0)	64 (61.3 to 66.8)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
1month after Vac3: PMB2707[B44]1:8(N=1210,0,0)	89.3 (87.4 to 90.9)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs/SAEs: recorded from first vaccination through 6 months after third vaccination. Subjects recorded pre-specified reactogenicity events (local reactions, systemic events) in electronic diary within 7 days after first, second and third vaccination

Adverse event reporting additional description

All AEs collected on case report form are shown below as having been collected via non-systematic assessment. All events reported via electronic diary (reactogenicity events) are shown below as having been collected via systematic assessment. Reactogenicity events are grouped by all severities and doses combined.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Group 1 rLP2086 Lot 1

Reporting group description

Lot 1 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 3 rLP2086 Lot 3

Reporting group description

Lot 3 on a 0-, 2-, 6- month schedule.

Reporting group title

Group 4 HAV/Saline

Reporting group description

Hepatitis A virus vaccine (HAV) on a 0- and 6-month schedule and saline at Month 2.

Reporting group title

Group 2 rLP2086 Lot 2

Reporting group description

Lot 2 on a 0-, 2-, 6- month schedule

Serious adverse events	Group 1 rLP2086 Lot 1	Group 3 rLP2086 Lot 3	Group 4 HAV/Saline	Group 2 rLP2086 Lot 2
Total subjects affected by serious adverse events
subjects affected / exposed	22 / 1508 (1.46%)	19 / 587 (3.24%)	22 / 897 (2.45%)	10 / 598 (1.67%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion threatened
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Influenza like illness
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Food allergy
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Pelvic pain
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Testicular torsion
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	1 / 1508 (0.07%)	1 / 587 (0.17%)	2 / 897 (0.22%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anorexia nervosa
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depression suicidal
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mental disorder
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aggression
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety disorder
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Borderline personality disorder
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Heart sounds abnormal
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Forearm fracture
subjects affected / exposed	2 / 1508 (0.13%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Alcohol poisoning
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bone contusion
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laceration
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neck injury
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post-traumatic neck syndrome
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Ventricular extrasystoles
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Complex partial seizures
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple sclerosis
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Blindness transient
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 1508 (0.13%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenitis
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Urinary retention
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Synovial cyst
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	4 / 897 (0.45%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	1 / 1508 (0.07%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	2 / 897 (0.22%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess neck
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	0 / 897 (0.00%)	1 / 598 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendiceal abscess
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis aseptic
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 1508 (0.07%)	0 / 587 (0.00%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 1508 (0.00%)	0 / 587 (0.00%)	1 / 897 (0.11%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Type 1 diabetes mellitus
subjects affected / exposed	0 / 1508 (0.00%)	1 / 587 (0.17%)	0 / 897 (0.00%)	0 / 598 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Group 1 rLP2086 Lot 1	Group 3 rLP2086 Lot 3	Group 4 HAV/Saline	Group 2 rLP2086 Lot 2
Total subjects affected by non serious adverse events
subjects affected / exposed	1410 / 1508 (93.50%)	542 / 587 (92.33%)	655 / 897 (73.02%)	547 / 598 (91.47%)
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	42 / 1508 (2.79%)	9 / 587 (1.53%)	20 / 897 (2.23%)	19 / 598 (3.18%)
occurrences all number	45	10	22	20
Ligament sprain
subjects affected / exposed	36 / 1508 (2.39%)	8 / 587 (1.36%)	24 / 897 (2.68%)	14 / 598 (2.34%)
occurrences all number	42	8	25	15
Contusion
subjects affected / exposed	20 / 1508 (1.33%)	6 / 587 (1.02%)	19 / 897 (2.12%)	7 / 598 (1.17%)
occurrences all number	20	6	19	7
Muscle strain
subjects affected / exposed	7 / 1508 (0.46%)	1 / 587 (0.17%)	9 / 897 (1.00%)	5 / 598 (0.84%)
occurrences all number	8	1	10	5
Nervous system disorders
Dizziness
subjects affected / exposed	5 / 1508 (0.33%)	3 / 587 (0.51%)	3 / 897 (0.33%)	6 / 598 (1.00%)
occurrences all number	5	3	3	6
Headache
subjects affected / exposed	42 / 1508 (2.79%)	15 / 587 (2.56%)	23 / 897 (2.56%)	21 / 598 (3.51%)
occurrences all number	46	17	29	23
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	18 / 1508 (1.19%)	5 / 587 (0.85%)	8 / 897 (0.89%)	8 / 598 (1.34%)
occurrences all number	19	5	9	8
Fatigue
subjects affected / exposed	5 / 1508 (0.33%)	6 / 587 (1.02%)	5 / 897 (0.56%)	3 / 598 (0.50%)
occurrences all number	6	6	6	3
Fever >=38.0 degrees C -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[1]	154 / 1504 (10.24%)	57 / 585 (9.74%)	46 / 892 (5.16%)	52 / 597 (8.71%)
occurrences all number	154	57	46	52
Vomiting -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[2]	110 / 1504 (7.31%)	44 / 585 (7.52%)	41 / 893 (4.59%)	31 / 597 (5.19%)
occurrences all number	110	44	41	31
Diarrhea-Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[3]	294 / 1504 (19.55%)	117 / 585 (20.00%)	187 / 893 (20.94%)	114 / 597 (19.10%)
occurrences all number	294	117	187	114
Headache -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[4]	1032 / 1504 (68.62%)	392 / 585 (67.01%)	477 / 893 (53.42%)	379 / 597 (63.48%)
occurrences all number	1032	392	477	379
Fatigue -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[5]	1011 / 1504 (67.22%)	369 / 585 (63.08%)	454 / 893 (50.84%)	380 / 597 (63.65%)
occurrences all number	1011	369	454	380
Chills-Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[6]	566 / 1504 (37.63%)	225 / 585 (38.46%)	227 / 893 (25.42%)	183 / 597 (30.65%)
occurrences all number	566	225	227	183
Muscle pain -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[7]	598 / 1504 (39.76%)	210 / 585 (35.90%)	254 / 893 (28.44%)	205 / 597 (34.34%)
occurrences all number	598	210	254	205
Joint pain -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[8]	532 / 1504 (35.37%)	191 / 585 (32.65%)	209 / 893 (23.40%)	170 / 597 (28.48%)
occurrences all number	532	191	209	170
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	29 / 1508 (1.92%)	9 / 587 (1.53%)	8 / 897 (0.89%)	5 / 598 (0.84%)
occurrences all number	29	10	8	5
Diarrhoea
subjects affected / exposed	15 / 1508 (0.99%)	3 / 587 (0.51%)	15 / 897 (1.67%)	6 / 598 (1.00%)
occurrences all number	15	3	16	6
Vomiting
subjects affected / exposed	14 / 1508 (0.93%)	2 / 587 (0.34%)	12 / 897 (1.34%)	4 / 598 (0.67%)
occurrences all number	15	2	14	4
Nausea
subjects affected / exposed	10 / 1508 (0.66%)	3 / 587 (0.51%)	7 / 897 (0.78%)	7 / 598 (1.17%)
occurrences all number	11	3	7	7
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	19 / 1508 (1.26%)	7 / 587 (1.19%)	9 / 897 (1.00%)	9 / 598 (1.51%)
occurrences all number	19	8	9	9
Rhinitis allergic
subjects affected / exposed	16 / 1508 (1.06%)	7 / 587 (1.19%)	14 / 897 (1.56%)	7 / 598 (1.17%)
occurrences all number	18	8	15	7
Oropharyngeal pain
subjects affected / exposed	19 / 1508 (1.26%)	5 / 587 (0.85%)	6 / 897 (0.67%)	3 / 598 (0.50%)
occurrences all number	23	5	6	4
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	14 / 1508 (0.93%)	14 / 587 (2.39%)	11 / 897 (1.23%)	6 / 598 (1.00%)
occurrences all number	14	14	12	6
Dermatitis contact
subjects affected / exposed	14 / 1508 (0.93%)	5 / 587 (0.85%)	5 / 897 (0.56%)	7 / 598 (1.17%)
occurrences all number	15	6	5	7
Pain at injection site -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[9]	1403 / 1504 (93.28%)	541 / 585 (92.48%)	525 / 897 (58.53%)	544 / 597 (91.12%)
occurrences all number	1403	541	525	544
Redness -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[10]	365 / 1504 (24.27%)	145 / 585 (24.79%)	21 / 893 (2.35%)	136 / 597 (22.78%)
occurrences all number	365	145	21	136
Swelling -Any (reactogenicity event)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[11]	416 / 1504 (27.66%)	158 / 585 (27.01%)	26 / 893 (2.91%)	161 / 597 (26.97%)
occurrences all number	416	158	26	161
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	18 / 1508 (1.19%)	3 / 587 (0.51%)	13 / 897 (1.45%)	11 / 598 (1.84%)
occurrences all number	18	3	13	12
Pain in extremity
subjects affected / exposed	13 / 1508 (0.86%)	2 / 587 (0.34%)	12 / 897 (1.34%)	3 / 598 (0.50%)
occurrences all number	13	2	12	3
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	105 / 1508 (6.96%)	45 / 587 (7.67%)	70 / 897 (7.80%)	53 / 598 (8.86%)
occurrences all number	122	50	81	57
Pharyngitis
subjects affected / exposed	69 / 1508 (4.58%)	24 / 587 (4.09%)	43 / 897 (4.79%)	21 / 598 (3.51%)
occurrences all number	76	27	52	22
Nasopharyngitis
subjects affected / exposed	59 / 1508 (3.91%)	32 / 587 (5.45%)	32 / 897 (3.57%)	32 / 598 (5.35%)
occurrences all number	70	36	36	42
Gastroenteritis
subjects affected / exposed	43 / 1508 (2.85%)	19 / 587 (3.24%)	25 / 897 (2.79%)	25 / 598 (4.18%)
occurrences all number	47	21	29	29
Bronchitis
subjects affected / exposed	27 / 1508 (1.79%)	10 / 587 (1.70%)	19 / 897 (2.12%)	6 / 598 (1.00%)
occurrences all number	29	10	20	6
Sinusitis
subjects affected / exposed	34 / 1508 (2.25%)	14 / 587 (2.39%)	22 / 897 (2.45%)	19 / 598 (3.18%)
occurrences all number	41	16	22	22
Otitis media
subjects affected / exposed	19 / 1508 (1.26%)	11 / 587 (1.87%)	16 / 897 (1.78%)	11 / 598 (1.84%)
occurrences all number	20	11	16	13
Pharyngitis streptococcal
subjects affected / exposed	21 / 1508 (1.39%)	10 / 587 (1.70%)	13 / 897 (1.45%)	6 / 598 (1.00%)
occurrences all number	25	11	13	6
Influenza
subjects affected / exposed	19 / 1508 (1.26%)	8 / 587 (1.36%)	9 / 897 (1.00%)	9 / 598 (1.51%)
occurrences all number	19	8	9	9
Acute sinusitis
subjects affected / exposed	18 / 1508 (1.19%)	7 / 587 (1.19%)	7 / 897 (0.78%)	8 / 598 (1.34%)
occurrences all number	20	7	7	9
Urinary tract infection
subjects affected / exposed	18 / 1508 (1.19%)	10 / 587 (1.70%)	7 / 897 (0.78%)	5 / 598 (0.84%)
occurrences all number	19	10	7	5
Viral infection
subjects affected / exposed	15 / 1508 (0.99%)	4 / 587 (0.68%)	12 / 897 (1.34%)	8 / 598 (1.34%)
occurrences all number	16	4	14	9
Viral pharyngitis
subjects affected / exposed	19 / 1508 (1.26%)	2 / 587 (0.34%)	9 / 897 (1.00%)	4 / 598 (0.67%)
occurrences all number	25	2	11	5
Tonsillitis
subjects affected / exposed	10 / 1508 (0.66%)	3 / 587 (0.51%)	10 / 897 (1.11%)	7 / 598 (1.17%)
occurrences all number	11	4	10	11
Otitis externa
subjects affected / exposed	8 / 1508 (0.53%)	3 / 587 (0.51%)	9 / 897 (1.00%)	9 / 598 (1.51%)
occurrences all number	8	3	9	9
Otitis media acute
subjects affected / exposed	8 / 1508 (0.53%)	2 / 587 (0.34%)	10 / 897 (1.11%)	6 / 598 (1.00%)
occurrences all number	9	2	11	6
Gastroenteritis viral
subjects affected / exposed	8 / 1508 (0.53%)	1 / 587 (0.17%)	9 / 897 (1.00%)	3 / 598 (0.50%)
occurrences all number	9	1	9	3

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here, number of subjects exposed signifies subjects with known values after the vaccination.

More information

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Were there any global substantial amendments to the protocol? Yes

24 Sep 2012

Footnotes added to the schedule of activities regarding contacting subjects to follow-up diary events persisting after day 7 of the e-diary and regarding the checklist for AE reporting.

24 Sep 2012

Adverse event reporting requirements updated - Serious adverse events occurring to a subject after the active reporting period has ended should be reported to the sponsor if the investigator becomes aware of them; at a minimum, all serious adverse events that the investigator believes have at least a reasonable possibility of being related to study drug are to be reported to the sponsor.

24 Sep 2012

Added details on inquiries about medical visits and missed days of school and work associated with adverse events to Procedures.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Randomized, Active-Controlled, Observer-Blinded Trial to Assess the Lot Consistency, Safety, Tolerability, and Immunogenicity of a Meningococcal Serogroup B Bivalent rLP2086 Vaccine in Healthy Subjects Aged ≥10 to <19 Years

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects with >=4 Fold Rise in Serum Bactericidal Assay Using Human Complement (hSBA) for 4 Primary Strains and Composite Response (hSBA >=Lower Limit of Quantification [LLOQ] for all 4 Primary Strains Combined)

Primary: Percentage of Subjects with >=4 Fold Rise in Serum Bactericidal Assay Using Human Complement (hSBA) for 4 Primary Strains and Composite Response (hSBA >=Lower Limit of Quantification [LLOQ] for all 4 Primary Strains Combined)

Primary: hSBA Geometric Mean Titers (GMTs) for Each of the 2 Primary Test Strains Measured 1 Month After the Third Vaccination with Bivalent rLP2086 Vaccine

Primary: hSBA Geometric Mean Titers (GMTs) for Each of the 2 Primary Test Strains Measured 1 Month After the Third Vaccination with Bivalent rLP2086 Vaccine

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After First Vaccination

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After First Vaccination

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Second Vaccination

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Second Vaccination

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Third Vaccination

Primary: Percentage of Subjects Reporting Local Reactions (LRs) Within 7 Days After Third Vaccination

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After First Vaccination

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After First Vaccination

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Second Vaccination

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Second Vaccination

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Third Vaccination

Primary: Percentage of Subjects Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Follow-up Phase

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Follow-up Phase

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Throughout the Study Period

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Throughout the Study Period

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Medically Attended AE During the Vaccination Phase

Primary: Percentage of Subjects With at Least 1 Medically Attended AE During the Vaccination Phase

Primary: Percentage of Subjects With at Least 1 Medically Attended AE During the Follow-Up Phase

Primary: Percentage of Subjects With at Least 1 Medically Attended AE During the Follow-Up Phase

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Throughout the Study Period

Primary: Percentage of Subjects With at Least 1 Medically Attended AE Throughout the Study Period

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-Up Phase

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-Up Phase

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study Period

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study Period

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) WIthin 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) WIthin 30 Days After First Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Second Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Third Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event Within 30 Days After any Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event During the Vaccination Phase

Primary: Percentage of Subjects With at Least 1 Adverse Event During the Vaccination Phase

Primary: Percentage of Subjects Reporting at Least 1 Immediate AE After First Vaccination

Primary: Percentage of Subjects Reporting at Least 1 Immediate AE After First Vaccination

Clinical Trial Results:
A Phase 3, Randomized, Active-Controlled, Observer-Blinded Trial to Assess the Lot Consistency, Safety, Tolerability, and Immunogenicity of a Meningococcal Serogroup B Bivalent rLP2086 Vaccine in Healthy Subjects Aged ≥10 to <19 Years