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Clinical Trial Results:
A Phase 3 Study to Assess the Persistence of hSBA Response up to 48 Months After Completion of a Primary Series of Bivalent rLP2086, and the Safety, Tolerability, and Immunogenicity of a Booster Dose of Bivalent rLP2086

Summary
EudraCT number	2011-005697-31
Trial protocol	CZ SE DE DK FI PL
Global end of trial date	05 Jan 2018

Results information
Results version number	v3
This version publication date	21 Sep 2019
First version publication date	21 Jul 2018
Other versions	v1 , v2 , v4
Version creation reason

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

B1971033

ISRCTN number

US NCT number

NCT01543087

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer, Inc.

Sponsor organisation address

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

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com

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

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

14 Jun 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Jan 2018

Was the trial ended prematurely?

Main objective of the trial

Stage 1 • To describe the immunogenicity of bivalent recombinant lipoprotein 2086 vaccine (rLP2086) as determined by serum bactericidal assay using human complement (hSBA) titers to 4 primary test strains at approximately 6, 12, 18, 24, 36, and 48 months after the last dose (second or third dose) of bivalent rLP2086 or saline in the primary study. Booster Stage • To describe the immune response as measured by hSBA titers to 4 primary test strains 1 month following the last vaccination with bivalent rLP2086 in the primary study, before the booster vaccination, and 1 month, 12 months, and 26 months after a single booster dose of bivalent rLP2086. • To evaluate the safety profile of bivalent rLP2086 as measured by the incidence of local reactions, systemic events, adverse events (AEs), serious adverse events (SAEs), newly diagnosed chronic medical conditions (NDCMCs), medically attended events, and immediate AEs following a booster vaccination of bivalent rLP2086.

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 Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Sep 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

26 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 153

Country: Number of subjects enrolled

Denmark: 216

Country: Number of subjects enrolled

Finland: 40

Country: Number of subjects enrolled

Germany: 54

Country: Number of subjects enrolled

Sweden: 42

Country: Number of subjects enrolled

United States: 193

Worldwide total number of subjects

698

EEA total number of subjects

505

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)

Adolescents (12-17 years)

468

Adults (18-64 years)

157

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Total 698 subjects enrolled in this extension study, who were enrolled in any 1 of the primary studies B1971010 (NCT01323270), B1971012 (NCT01299480), and B1971015 (NCT01461980).

Screening details

This study consisted of 2 stages: Stage 1 and Booster stage. Only subjects from primary studies B1971010 and B1971012 who received bivalent rLP2086 in the primary study and completed Stage 1 in this study, were eligible to participate in the booster stage.

Period 1 title

Stage 1

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)

Arm description

Subjects received quadrivalent meningococcal polysaccharide conjugate (MCV4) tetanus + acellular pertussis (Tdap) +Saline at Month 0, Saline only at Month 2 and 6 schedule in primary study B1971015 and were followed up for 48 months during the stage 1 of this study.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)

Arm description

Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 micrograms (mcg) of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)

Arm description

Subject who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study. Only subjects from B1971010 and B1971012 studies received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 4: rLP2086 (0-and 6-Month Schedule)

Arm description

Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 5: rLP2086 (0- and 2-Month Schedule)

Arm description

Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 6: rLP2086 (0- and 4-Month Schedule)

Arm description

Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Number of subjects in period 1	Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Started	70	103	277	116	86	46
Safety Population	70	101	277	116	86	46
Completed	56	93	237	108	83	46
Not completed	14	10	40	8	3	0
No longer meets eligibility criteria	1	-	1	2	-	-
No longer willing to participate	5	3	18	6	3	-
Other than specified	5	-	9	-	-	-
Lost to follow-up	3	4	12	-	-	-
Protocol deviation	-	3	-	-	-	-

Period 2 title

Booster Stage

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 4: rLP2086 (0-and 6-Month Schedule)

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 5: rLP2086 (0- and 2-Month Schedule)

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Group 6: rLP2086 (0- and 4-Month Schedule)

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent rLP2086

Investigational medicinal product code

PF-05212366

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

Number of subjects in period 2 ^[1]	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Started	60	92	64	56	32
Vaccinated	59	92	64	54	32
Completed	59	91	64	54	32
Not completed	1	1	0	2	0
Withdrawal before booster vaccination	1	-	-	2	-
Lost to follow-up	-	1	-	-	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only subjects from primary studies B1971010 and B1971012 who completed Stage 1, received bivalent rLP2086 in primary study and agreed to participate in booster stage, where included in this period.

Baseline characteristics

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Reporting group title

Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 4: rLP2086 (0-and 6-Month Schedule)

Reporting group description

Reporting group title

Group 5: rLP2086 (0- and 2-Month Schedule)

Reporting group description

Reporting group title

Group 6: rLP2086 (0- and 4-Month Schedule)

Reporting group description

Reporting group values	Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Total
Number of subjects	70	103	277	116	86	46	698
Age categorical
Units: Subjects
Age Continuous
The age of subjects enrolled in B1971033 is the age of subjects at Stage 1 enrollment.
Units: years
arithmetic mean (standard deviation)	11.7 ( 0.7 )	15.9 ( 2.2 )	14.3 ( 2.8 )	15.8 ( 2.1 )	16.1 ( 2.4 )	15.9 ( 2.1 )	-
Sex: Female, Male
Units: Subjects
Female	32	55	144	67	38	26	362
Male	38	48	133	49	48	20	336
Race/Ethnicity, Customized
Units: Subjects
White	59	103	256	115	85	46	664
Black	9	0	12	1	0	0	22
Other	2	0	8	0	1	0	11
Asian	0	0	1	0	0	0	1
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	16	0	25	1	2	0	44
Not Hispanic or Latino	54	103	252	115	84	46	654
Unknown or Not Reported	0	0	0	0	0	0	0

End points

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Reporting group title

Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 4: rLP2086 (0-and 6-Month Schedule)

Reporting group description

Reporting group title

Group 5: rLP2086 (0- and 2-Month Schedule)

Reporting group description

Reporting group title

Group 6: rLP2086 (0- and 4-Month Schedule)

Reporting group description

Reporting group title

Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)

Reporting group description

Reporting group title

Group 4: rLP2086 (0-and 6-Month Schedule)

Reporting group description

Reporting group title

Group 5: rLP2086 (0- and 2-Month Schedule)

Reporting group description

Reporting group title

Group 6: rLP2086 (0- and 4-Month Schedule)

Reporting group description

Subject analysis set title

Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

Subject analysis set title

Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033

Subject analysis set title

Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subjects received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971015.

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations

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End point title

Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations ^[1] ^[2]

End point description

For immunogenicity assessment, serum bactericidal assay using human complement (hSBA) was performed with 4 primary Neisseria meningitidis serogroup B (MnB) test strains. Percentage of subjects achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95 percent (%) confidence interval (CIs). LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). Modified intent-to-treat (mITT) population included subjects who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain. Subjects who received bivalent rLP2086 in primary study B1971012, were entered in this study at Month 12 (Visit 2). Hence, no subjects enrolled from primary study B1971012 had serology results at Month 6.

End point type

Primary

End point timeframe

Month 6 (Visit 1 of study B1971033)

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:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	70	40	123
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 7, 37, 18)	14.3 (0.4 to 57.9)	86.5 (71.2 to 95.5)	83.3 (58.6 to 96.4)
PMB2001 (A56) (n= 6, 36, 18)	16.7 (0.4 to 64.1)	72.2 (54.8 to 85.8)	88.9 (65.3 to 98.6)
PMB2948 (B24) (n= 7, 38, 17)	0.0 (0.0 to 41.0)	36.8 (21.8 to 54.0)	35.3 (14.2 to 61.7)
PMB2707 (B44) (n= 7, 37, 16)	0.0 (0.0 to 41.0)	64.9 (47.5 to 79.8)	56.3 (29.9 to 80.2)

No statistical analyses for this end point

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 12 (Visit 2) After Primary Vaccinations

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End point title

Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 12 (Visit 2) After Primary Vaccinations ^[3] ^[4]

End point description

End point type

Primary

End point timeframe

Month 12 (Visit 2 of study B1971033)

Notes
[3] - 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.
[4] - 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:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	70	101	116	86	46	40	114	123
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 69, 99, 113, 84, 46, 39, 111, 122)	29.0 (18.7 to 41.2)	41.4 (31.6 to 51.8)	36.3 (27.4 to 45.9)	44.0 (33.2 to 55.3)	41.3 (27.0 to 56.8)	69.2 (52.4 to 83.0)	45.0 (35.6 to 54.8)	61.5 (52.2 to 70.1)
PMB2001(A56)(n= 69, 98, 106, 84, 42, 39, 109, 111)	17.4 (9.3 to 28.4)	73.5 (63.6 to 81.9)	60.4 (50.4 to 69.7)	69.0 (58.0 to 78.7)	71.4 (55.4 to 84.3)	66.7 (49.8 to 80.9)	76.1 (67.0 to 83.8)	63.1 (53.4 to 72.0)
PMB2948(B24)(n= 70, 98, 103, 82, 46, 40, 108, 121)	1.4 (0.0 to 7.7)	40.8 (31.0 to 51.2)	36.9 (27.6 to 47.0)	41.5 (30.7 to 52.9)	37.0 (23.2 to 52.5)	37.5 (22.7 to 54.2)	49.1 (39.3 to 58.9)	24.0 (16.7 to 32.6)
PMB2707(B44)(n=70, 100, 115, 85, 45, 40, 111, 120)	1.4 (0.0 to 7.7)	24.0 (16.0 to 33.6)	16.5 (10.3 to 24.6)	21.2 (13.1 to 31.4)	22.2 (11.2 to 37.1)	47.5 (31.5 to 63.9)	22.5 (15.1 to 31.4)	32.5 (24.2 to 41.7)

No statistical analyses for this end point

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 18 (Visit 3) After Primary Vaccinations

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End point title

Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 18 (Visit 3) After Primary Vaccinations ^[5] ^[6]

End point description

End point type

Primary

End point timeframe

Month 18 (Visit 3 of study B1971033)

Notes
[5] - 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.
[6] - 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:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	70	101	116	86	46	40	114	123
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 69, 97, 111, 85, 45, 38, 112, 117)	23.2 (13.9 to 34.9)	37.1 (27.5 to 47.5)	47.7 (38.2 to 57.4)	47.1 (36.1 to 58.2)	51.1 (35.8 to 66.3)	57.9 (40.8 to 73.7)	44.6 (35.2 to 54.3)	51.3 (41.9 to 60.6)
PMB2001(A56)(n= 67, 94, 102, 83, 43, 39, 106, 114)	11.9 (5.3 to 22.2)	64.9 (54.4 to 74.5)	57.8 (47.7 to 67.6)	62.7 (51.3 to 73.0)	62.8 (46.7 to 77.0)	56.4 (39.6 to 72.2)	72.6 (63.1 to 80.9)	53.5 (43.9 to 62.9)
PMB2948(B24)(n= 69, 96, 105, 81, 44, 38, 109, 113)	5.8 (1.6 to 14.2)	45.8 (35.6 to 56.3)	31.4 (22.7 to 41.2)	39.5 (28.8 to 51.0)	50.0 (34.6 to 65.4)	39.5 (24.0 to 56.6)	46.8 (37.2 to 56.6)	23.9 (16.4 to 32.8)
PMB2707(B44)(n= 69, 98, 113, 86, 46, 38, 110, 115)	0.0 (0.0 to 5.2)	26.5 (18.1 to 36.4)	15.9 (9.7 to 24.0)	24.4 (15.8 to 34.9)	28.3 (16.0 to 43.5)	31.6 (17.5 to 48.7)	18.2 (11.5 to 26.7)	29.6 (21.4 to 38.8)

No statistical analyses for this end point

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 24 (Visit 4) After Primary Vaccinations

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End point title

Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 24 (Visit 4) After Primary Vaccinations ^[7] ^[8]

End point description

End point type

Primary

End point timeframe

Month 24 (Visit 4 of study B1971033)

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.
[8] - 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:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	70	101	116	86	46	40	114	123
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 68, 98, 109, 84, 46, 38, 107, 115)	17.6 (9.5 to 28.8)	34.7 (25.4 to 45.0)	42.2 (32.8 to 52.0)	44.0 (33.2 to 55.3)	39.1 (25.1 to 54.6)	50.0 (33.4 to 66.6)	40.2 (30.8 to 50.1)	49.6 (40.1 to 59.0)
PMB2001(A56)(n= 66, 91, 104, 80, 45, 38, 102, 110)	3.0 (0.4 to 10.5)	69.2 (58.7 to 78.5)	53.8 (43.8 to 63.7)	58.8 (47.2 to 69.6)	60.0 (44.3 to 74.3)	57.9 (40.8 to 73.7)	68.6 (58.7 to 77.5)	36.4 (27.4 to 46.1)
PMB2948(B24)(n= 68, 93, 110, 83, 45, 38, 107, 112)	4.4 (0.9 to 12.4)	43.0 (32.8 to 53.7)	31.8 (23.3 to 41.4)	37.3 (27.0 to 48.7)	51.1 (35.8 to 66.3)	39.5 (24.0 to 56.6)	43.0 (33.5 to 52.9)	25.9 (18.1 to 35.0)
PMB2707(B44)(n= 67, 97, 108, 83, 46, 39, 109, 114)	3.0 (0.4 to 10.4)	23.7 (15.7 to 33.4)	15.7 (9.4 to 24.0)	22.9 (14.4 to 33.4)	28.3 (16.0 to 43.5)	38.5 (23.4 to 55.4)	18.3 (11.6 to 26.9)	27.2 (19.3 to 36.3)

No statistical analyses for this end point

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 36 (Visit 5) After Primary Vaccinations

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End point title

Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 36 (Visit 5) After Primary Vaccinations ^[9] ^[10]

End point description

End point type

Primary

End point timeframe

Month 36 (Visit 5 of study B1971033)

Notes
[9] - 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.
[10] - 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:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	70	101	116	86	46	40	114	123
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 58, 96, 108, 82, 44, 38, 102, 107)	27.6 (16.7 to 40.9)	41.7 (31.7 to 52.2)	42.6 (33.1 to 52.5)	42.7 (31.8 to 54.1)	34.1 (20.5 to 49.9)	60.5 (43.4 to 76.0)	39.2 (29.7 to 49.4)	49.5 (39.7 to 59.4)
PMB2001 (A56) (n= 57, 94, 99, 81, 42, 37, 92, 103)	7.0 (1.9 to 17.0)	58.5 (47.9 to 68.6)	58.6 (48.2 to 68.4)	59.3 (47.8 to 70.1)	50.0 (34.2 to 65.8)	54.1 (36.9 to 70.5)	67.4 (56.8 to 76.8)	35.0 (25.8 to 45.0)
PMB2948(B24)(n= 59, 93, 107, 81, 43, 36, 100, 103)	3.4 (0.4 to 11.7)	41.9 (31.8 to 52.6)	33.6 (24.8 to 43.4)	48.1 (36.9 to 59.5)	41.9 (27.0 to 57.9)	38.9 (23.1 to 56.5)	42.0 (32.2 to 52.3)	30.1 (21.5 to 39.9)
PMB2707(B44)(n= 59, 97, 109, 83, 44, 39, 103, 103)	1.7 (0.0 to 9.1)	21.6 (13.9 to 31.2)	20.2 (13.1 to 28.9)	21.7 (13.4 to 32.1)	18.2 (8.2 to 32.7)	33.3 (19.1 to 50.2)	16.5 (9.9 to 25.1)	24.3 (16.4 to 33.7)

No statistical analyses for this end point

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 48 (Visit 6) After Primary Vaccinations

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End point title

Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 48 (Visit 6) After Primary Vaccinations ^[11] ^[12]

End point description

End point type

Primary

End point timeframe

Month 48 (Visit 6 of study B1971033)

Notes
[11] - 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.
[12] - 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:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	70	101	116	86	46	40	114	123
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 55, 90, 101, 81, 46, 35, 100, 101)	16.4 (7.8 to 28.8)	41.1 (30.8 to 52.0)	39.6 (30.0 to 49.8)	45.7 (34.6 to 57.1)	41.3 (27.0 to 56.8)	51.4 (34.0 to 68.6)	43.0 (33.1 to 53.3)	34.7 (25.5 to 44.8)
PMB2001 (A56) (n= 51, 85, 99, 75, 46, 33, 99, 94)	2.0 (0.0 to 10.4)	47.1 (36.1 to 58.2)	57.6 (47.2 to 67.5)	61.3 (49.4 to 72.4)	47.8 (32.9 to 63.1)	42.4 (25.5 to 60.8)	58.6 (48.2 to 68.4)	30.9 (21.7 to 41.2)
PMB2948(B24)(n= 56, 90, 105, 82, 45, 34, 98, 101)	7.1 (2.0 to 17.3)	41.1 (30.8 to 52.0)	30.5 (21.9 to 40.2)	45.1 (34.1 to 56.5)	42.2 (27.7 to 57.8)	50.0 (32.4 to 67.6)	40.8 (31.0 to 51.2)	23.8 (15.9 to 33.3)
PMB2707(B44)(n= 56, 92, 106, 82, 46, 34, 100, 100)	3.6 (0.4 to 12.3)	20.7 (12.9 to 30.4)	18.9 (11.9 to 27.6)	24.4 (15.6 to 35.1)	23.9 (12.6 to 38.8)	41.2 (24.6 to 59.3)	18.0 (11.0 to 26.9)	23.0 (15.2 to 32.5)

No statistical analyses for this end point

Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After Last Vaccination in Primary Study

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End point title

Percentage of Booster Stage Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After Last Vaccination in Primary Study ^[13]

End point description

For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. Percentage of subjects achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95 % CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). Evaluable population included all eligible subjects who received scheduled investigational products, had received no prohibited vaccines or treatment, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage.

End point type

Primary

End point timeframe

1 month after last vaccination in primary study

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	59	62	54	32	31	58
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 59, 61, 54, 32, 31, 57)	89.8 (79.2 to 96.2)	98.4 (91.2 to 100.0)	77.8 (64.4 to 88.0)	84.4 (67.2 to 94.7)	100.0 (88.8 to 100.0)	91.2 (80.7 to 97.1)
PMB2001 (A56) (n= 58, 62, 54, 32, 31, 57)	100.0 (93.8 to 100.0)	98.4 (91.3 to 100.0)	100.0 (93.4 to 100.0)	96.9 (83.8 to 99.9)	100.0 (88.8 to 100.0)	98.2 (90.6 to 100.0)
PMB2948 (B24) (n= 59, 60, 52, 29, 31, 58)	88.1 (77.1 to 95.1)	85.0 (73.4 to 92.9)	71.2 (56.9 to 82.9)	79.3 (60.3 to 92.0)	93.5 (78.6 to 99.2)	91.4 (81.0 to 97.1)
PMB2707 (B44) (n= 58, 60, 52, 32, 31, 57)	86.2 (74.6 to 93.9)	81.7 (69.6 to 90.5)	73.1 (59.0 to 84.4)	87.5 (71.0 to 96.5)	96.8 (83.3 to 99.9)	89.5 (78.5 to 96.0)

No statistical analyses for this end point

Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level >= Lower Limit of Quantitation for Each of the 4 Primary Strains Before Booster Vaccination (48 Months After Last Vaccination in Primary Study [Visit 6])

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End point title

Percentage of Booster Stage Subjects Achieving hSBA Titer Level >= Lower Limit of Quantitation for Each of the 4 Primary Strains Before Booster Vaccination (48 Months After Last Vaccination in Primary Study [Visit 6]) ^[14]

End point description

End point type

Primary

End point timeframe

Visit 6 of study B1971033 (48 months after last vaccination in primary study)

Notes
[14] - 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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	59	62	54	32	31	58
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 59, 61, 54, 31, 31, 57)	49.2 (35.9 to 62.5)	55.7 (42.4 to 68.5)	57.4 (43.2 to 70.8)	48.4 (30.2 to 66.9)	48.4 (30.2 to 66.9)	56.1 (42.4 to 69.3)
PMB2001 (A56) (n= 53, 62, 52, 30, 29, 55)	43.4 (29.8 to 57.7)	43.5 (31.0 to 56.7)	51.9 (37.6 to 66.0)	43.3 (25.5 to 62.6)	41.4 (23.5 to 61.1)	56.4 (42.3 to 69.7)
PMB2948 (B24) (n= 59, 62, 54, 31, 30, 57)	40.7 (28.1 to 54.3)	40.3 (28.1 to 53.6)	46.3 (32.6 to 60.4)	45.2 (27.3 to 64.0)	46.7 (28.3 to 65.7)	49.1 (35.6 to 62.7)
PMB2707 (B44) (n= 57, 62, 53, 32, 30, 57)	36.8 (24.4 to 50.7)	12.9 (5.7 to 23.9)	37.7 (24.8 to 52.1)	34.4 (18.6 to 53.2)	33.3 (17.3 to 52.8)	35.1 (22.9 to 48.9)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After the Booster Vaccination (Visit 8)

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End point title

Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After the Booster Vaccination (Visit 8) ^[15]

End point description

For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. Percentage of subjects achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95 % CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). Evaluable population included all eligible subjects who received scheduled investigational products,had received no prohibited vaccines or treatment, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage.

End point type

Primary

End point timeframe

Visit 8 (1 month following the booster vaccination on Month 49)

Notes
[15] - 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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	59	62	54	32	31	58
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 59, 60, 53, 32, 31, 58)	100.0 (93.9 to 100.0)	96.7 (88.5 to 99.6)	98.1 (89.9 to 100.0)	100.0 (89.1 to 100.0)	96.8 (83.3 to 99.9)	100.0 (93.8 to 100.0)
PMB2001 (A56) (n= 57, 62, 51, 32, 30, 56)	100.0 (93.7 to 100.0)	98.4 (91.3 to 100.0)	100.0 (93.0 to 100.0)	100.0 (89.1 to 100.0)	100.0 (88.4 to 100.0)	100.0 (93.6 to 100.0)
PMB2948 (B24) (n= 58, 62, 54, 32, 31, 57)	100.0 (93.8 to 100.0)	96.8 (88.8 to 99.6)	94.4 (84.6 to 98.8)	100.0 (89.1 to 100.0)	96.8 (83.3 to 99.9)	100.0 (93.7 to 100.0)
PMB2707 (B44) (n= 59, 61, 53, 32, 31, 58)	100.0 (93.9 to 100.0)	93.4 (84.1 to 98.2)	100.0 (93.3 to 100.0)	100.0 (89.1 to 100.0)	100.0 (88.8 to 100.0)	100.0 (93.8 to 100.0)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBATiter Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 12 Months After the Booster Vaccination(Visit 10)

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End point title

Percentage of Subjects Achieving hSBATiter Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 12 Months After the Booster Vaccination(Visit 10) ^[16]

End point description

End point type

Primary

End point timeframe

Visit 10 (12 months following the booster vaccination on Month 60)

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)	Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	59	62	54	32	31	58
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 58, 60, 51, 31, 28, 54)	74.1 (61.0 to 84.7)	80.0 (67.7 to 89.2)	82.4 (69.1 to 91.6)	96.8 (83.3 to 99.9)	89.3 (71.8 to 97.7)	77.8 (64.4 to 88.0)
PMB2001 (A56) (n= 55, 59, 50, 32, 24, 55)	90.9 (80.0 to 97.0)	81.4 (69.1 to 90.3)	74.0 (59.7 to 85.4)	100.0 (89.1 to 100.0)	87.5 (67.6 to 97.3)	89.1 (77.8 to 95.9)
PMB2948 (B24) (n= 58, 62, 49, 32, 30, 54)	65.5 (51.9 to 77.5)	77.4 (65.0 to 87.1)	65.3 (50.4 to 78.3)	84.4 (67.2 to 94.7)	66.7 (47.2 to 82.7)	74.1 (60.3 to 85.0)
PMB2707 (B44) (n= 56, 61, 52, 30, 30, 53)	75.0 (61.6 to 85.6)	59.0 (45.7 to 71.4)	78.8 (65.3 to 88.9)	93.3 (77.9 to 99.2)	76.7 (57.7 to 90.1)	81.1 (68.0 to 90.6)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to(>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 26 Months After the Booster Vaccination(Visit 11)

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End point title

Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to(>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 26 Months After the Booster Vaccination(Visit 11) ^[17]

End point description

For immunogenicity assessment, hSBA was performed with 4 MnB test strains. Percentage of subjects achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95 % CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). Evaluable population set was used in the analysis. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage. Subjects who received bivalent rLP2086 in primary study B1971010 were not analysed for this endpoint. Only subjects who received bivalent rLP2086 in primary study B1971012 on a 0-, 2-, and 6-month or a 0- and 6-month vaccination schedule were eligible to be followed for 26 months after booster vaccination.

End point type

Primary

End point timeframe

Visit 11 (26 months following the booster vaccination on Month 74)

Notes
[17] - 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	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	62	58
Units: percentage of subjects
number (confidence interval 95%)
PMB80 (A22) (n= 42, 34)	61.9 (45.6 to 76.4)	73.5 (55.6 to 87.1)
PMB2001 (A56) (n= 40, 29)	57.5 (40.9 to 73.0)	82.8 (64.2 to 94.2)
PMB2948 (B24) (n= 42, 33)	59.5 (43.3 to 74.4)	78.8 (61.1 to 91.0)
PMB2707 (B44) (n= 43, 33)	62.8 (46.7 to 77.0)	66.7 (48.2 to 82.0)

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Local Reactions Within 7 Days After Booster Vaccination

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End point title

Percentage of Subjects Reporting Local Reactions Within 7 Days After Booster Vaccination ^[18]

End point description

Local reactions were collected by using an e-diary and included pain at injection site, redness and swelling. Redness and swelling were graded as: none (0-2.0 centimetre [cm]), mild (2.5-5.0 cm), moderate (greater than [>] 5.0-10.0 cm) and severe (>10.0 cm). Pain was graded as: mild (does not interfere with activity), moderate (Interferes with activity) and severe (prevents daily activity). Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.

End point type

Primary

End point timeframe

Within 7 days after booster vaccination on Month 48

Notes
[18] - 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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)
Pain at injection site:Any	91.5 (81.3 to 97.2)	93.5 (86.3 to 97.6)	89.1 (78.8 to 95.5)	88.9 (77.4 to 95.8)	84.4 (67.2 to 94.7)
Pain at injection site:Mild	37.3 (25.0 to 50.9)	29.3 (20.3 to 39.8)	28.1 (17.6 to 40.8)	35.2 (22.7 to 49.4)	25.0 (11.5 to 43.4)
Pain at injection site:Moderate	40.7 (28.1 to 54.3)	54.3 (43.6 to 64.8)	51.6 (38.7 to 64.2)	44.4 (30.9 to 58.6)	46.9 (29.1 to 65.3)
Pain at injection site:Severe	13.6 (6.0 to 25.0)	9.8 (4.6 to 17.8)	9.4 (3.5 to 19.3)	9.3 (3.1 to 20.3)	12.5 (3.5 to 29.0)
Redness:Any	20.3 (11.0 to 32.8)	20.7 (12.9 to 30.4)	20.3 (11.3 to 32.2)	27.8 (16.5 to 41.6)	6.3 (0.8 to 20.8)
Redness:Mild	6.8 (1.9 to 16.5)	5.4 (1.8 to 12.2)	10.9 (4.5 to 21.2)	5.6 (1.2 to 15.4)	3.1 (0.1 to 16.2)
Redness:Moderate	11.9 (4.9 to 22.9)	10.9 (5.3 to 19.1)	7.8 (2.6 to 17.3)	16.7 (7.9 to 29.3)	3.1 (0.1 to 16.2)
Redness:Severe	1.7 (0.0 to 9.1)	4.3 (1.2 to 10.8)	1.6 (0.0 to 8.4)	5.6 (1.2 to 15.4)	0.0 (0.0 to 10.9)
Swelling:Any	18.6 (9.7 to 30.9)	20.7 (12.9 to 30.4)	17.2 (8.9 to 28.7)	14.8 (6.6 to 27.1)	9.4 (2.0 to 25.0)
Swelling:Mild	11.9 (4.9 to 22.9)	8.7 (3.8 to 16.4)	10.9 (4.5 to 21.2)	3.7 (0.5 to 12.7)	9.4 (2.0 to 25.0)
Swelling:Moderate	6.8 (1.9 to 16.5)	10.9 (5.3 to 19.1)	6.3 (1.7 to 15.2)	11.1 (4.2 to 22.6)	0.0 (0.0 to 10.9)
Swelling:Severe	0.0 (0.0 to 6.1)	1.1 (0.0 to 5.9)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination

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End point title

Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination ^[19]

End point description

Systemic reactions included: fever, vomiting, diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at the injection site and joint pain, all other systemic reactions were recorded by using an e-diary. Fever was categorized as: 38.0 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and > 40.0 degree C. Vomiting was graded as: mild (1 to 2 times in 24 hours [hrs]), moderate (>2 times in 24 hrs) and severe (requires intravenous [IV] hydration); Diarrhea was graded as: mild (2 to 3 loose stools in 24 hrs), moderate (4 to 5 loose stools in 24 hrs) and severe (6 or more loose stools in 24 hrs); Headache, fatigue, chills, muscle pain and joint pain was graded as: mild (does not interfere with daily activities), moderate (some interference with activity) and severe (prevents daily routine activity). Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086) and for whom safety data was available.

End point type

Primary

End point timeframe

Within 7 days after booster vaccination on Month 48

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)
Fever >=38 degrees C	5.1 (1.1 to 14.1)	1.1 (0.0 to 5.9)	4.7 (1.0 to 13.1)	1.9 (0.0 to 9.9)	3.1 (0.1 to 16.2)
Fever 38.0 to <38.5 degrees C	5.1 (1.1 to 14.1)	1.1 (0.0 to 5.9)	3.1 (0.4 to 10.8)	0.0 (0.0 to 6.6)	3.1 (0.1 to 16.2)
Fever 38.5 to <39.0 degrees C	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	1.6 (0.0 to 8.4)	1.9 (0.0 to 9.9)	0.0 (0.0 to 10.9)
Fever 39.0 to 40.0 degrees C	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
Fever >40.0 degrees C	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
Vomiting:Any	1.7 (0.0 to 9.1)	3.3 (0.7 to 9.2)	3.1 (0.4 to 10.8)	1.9 (0.0 to 9.9)	0.0 (0.0 to 10.9)
Vomiting:Mild	1.7 (0.0 to 9.1)	3.3 (0.7 to 9.2)	1.6 (0.0 to 8.4)	1.9 (0.0 to 9.9)	0.0 (0.0 to 10.9)
Vomiting:Moderate	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	1.6 (0.0 to 8.4)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
Vomiting:Severe	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
Diarrhea:Any	10.2 (3.8 to 20.8)	13.0 (6.9 to 21.7)	4.7 (1.0 to 13.1)	5.6 (1.2 to 15.4)	18.8 (7.2 to 36.4)
Diarrhea:Mild	8.5 (2.8 to 18.7)	12.0 (6.1 to 20.4)	3.1 (0.4 to 10.8)	5.6 (1.2 to 15.4)	18.8 (7.2 to 36.4)
Diarrhea:Moderate	1.7 (0.0 to 9.1)	1.1 (0.0 to 5.9)	1.6 (0.0 to 8.4)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
Diarrhea:Severe	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
Headache:Any	50.8 (37.5 to 64.1)	47.8 (37.3 to 58.5)	56.3 (43.3 to 68.6)	48.1 (34.3 to 62.2)	37.5 (21.1 to 56.3)
Headache:Mild	30.5 (19.2 to 43.9)	28.3 (19.4 to 38.6)	35.9 (24.3 to 48.9)	22.2 (12.0 to 35.6)	25.0 (11.5 to 43.4)
Headache:Moderate	20.3 (11.0 to 32.8)	18.5 (11.1 to 27.9)	20.3 (11.3 to 32.2)	25.9 (15.0 to 39.7)	12.5 (3.5 to 29.0)
Headache:Severe	0.0 (0.0 to 6.1)	1.1 (0.0 to 5.9)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
Fatigue:Any	62.7 (49.1 to 75.0)	60.9 (50.1 to 70.9)	62.5 (49.5 to 74.3)	51.9 (37.8 to 65.7)	65.6 (46.8 to 81.4)
Fatigue:Mild	27.1 (16.4 to 40.3)	27.2 (18.4 to 37.4)	35.9 (24.3 to 48.9)	24.1 (13.5 to 37.6)	31.3 (16.1 to 50.0)
Fatigue:Moderate	32.2 (20.6 to 45.6)	31.5 (22.2 to 42.0)	23.4 (13.8 to 35.7)	24.1 (13.5 to 37.6)	31.3 (16.1 to 50.0)
Fatigue:Severe	3.4 (0.4 to 11.7)	2.2 (0.3 to 7.6)	3.1 (0.4 to 10.8)	3.7 (0.5 to 12.7)	3.1 (0.1 to 16.2)
Chills:Any	23.7 (13.6 to 36.6)	31.5 (22.2 to 42.0)	20.3 (11.3 to 32.2)	18.5 (9.3 to 31.4)	28.1 (13.7 to 46.7)
Chills:Mild	13.6 (6.0 to 25.0)	20.7 (12.9 to 30.4)	12.5 (5.6 to 23.2)	9.3 (3.1 to 20.3)	18.8 (7.2 to 36.4)
Chills:Moderate	10.2 (3.8 to 20.8)	9.8 (4.6 to 17.8)	7.8 (2.6 to 17.3)	7.4 (2.1 to 17.9)	9.4 (2.0 to 25.0)
Chills:Severe	0.0 (0.0 to 6.1)	1.1 (0.0 to 5.9)	0.0 (0.0 to 5.6)	1.9 (0.0 to 9.9)	0.0 (0.0 to 10.9)
Muscle pain:Any	22.0 (12.3 to 34.7)	29.3 (20.3 to 39.8)	18.8 (10.1 to 30.5)	24.1 (13.5 to 37.6)	15.6 (5.3 to 32.8)
Muscle pain: Mild	16.9 (8.4 to 29.0)	15.2 (8.6 to 24.2)	7.8 (2.6 to 17.3)	14.8 (6.6 to 27.1)	6.3 (0.8 to 20.8)
Muscle pain:Moderate	5.1 (1.1 to 14.1)	13.0 (6.9 to 21.7)	7.8 (2.6 to 17.3)	5.6 (1.2 to 15.4)	9.4 (2.0 to 25.0)
Muscle pain:Severe	0.0 (0.0 to 6.1)	1.1 (0.0 to 5.9)	3.1 (0.4 to 10.8)	3.7 (0.5 to 12.7)	0.0 (0.0 to 10.9)
Joint pain:Any	11.9 (4.9 to 22.9)	16.3 (9.4 to 25.5)	14.1 (6.6 to 25.0)	18.5 (9.3 to 31.4)	21.9 (9.3 to 40.0)
Joint pain:Mild	8.5 (2.8 to 18.7)	9.8 (4.6 to 17.8)	7.8 (2.6 to 17.3)	7.4 (2.1 to 17.9)	12.5 (3.5 to 29.0)
Joint pain:Moderate	3.4 (0.4 to 11.7)	6.5 (2.4 to 13.7)	4.7 (1.0 to 13.1)	9.3 (3.1 to 20.3)	9.4 (2.0 to 25.0)
Joint pain:Severe	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	1.6 (0.0 to 8.4)	1.9 (0.0 to 9.9)	0.0 (0.0 to 10.9)
Use of antipyretic medication	10.2 (3.8 to 20.8)	14.1 (7.7 to 23.0)	7.8 (2.6 to 17.3)	13.0 (5.4 to 24.9)	6.3 (0.8 to 20.8)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Medically Attended Adverse Event (MAE) From Booster Vaccination Phase (Visit 7 to Visit 8)

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End point title

Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Medically Attended Adverse Event (MAE) From Booster Vaccination Phase (Visit 7 to Visit 8) ^[20]

End point description

An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious AEs and SAEs. An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.

End point type

Primary

End point timeframe

From Visit 7 (Month 48) to Visit 8 (Month 49) in Booster stage

Notes
[20] - 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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)
AE	6.8 (1.9 to 16.5)	8.7 (3.8 to 16.4)	12.5 (5.6 to 23.2)	3.7 (0.5 to 12.7)	12.5 (3.5 to 29.0)
SAE	0.0 (0.0 to 6.1)	1.1 (0.0 to 5.9)	0.0 (0.0 to 5.6)	1.9 (0.0 to 9.9)	0.0 (0.0 to 10.9)
NDCMC	0.0 (0.0 to 6.1)	0.0 (0.0 to 3.9)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
MAE	5.1 (1.1 to 14.1)	4.3 (1.2 to 10.8)	4.7 (1.0 to 13.1)	0.0 (0.0 to 6.6)	3.1 (0.1 to 16.2)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Follow-Up Phase (Visit 8 to Visit 9)

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End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Follow-Up Phase (Visit 8 to Visit 9) ^[21]

End point description

An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An MAE was defined as a non-serious AE (AE other than SAE) that resulted in an evaluation at a medical facility. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.

End point type

Primary

End point timeframe

Visit 8 (Month 49) to Visit 9 (Month 54) in Booster stage

Notes
[21] - 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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)
SAE	1.7 (0.0 to 9.1)	0.0 (0.0 to 3.9)	3.1 (0.4 to 10.8)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)
MAE	28.8 (17.8 to 42.1)	12.0 (6.1 to 20.4)	10.9 (4.5 to 21.2)	11.1 (4.2 to 22.6)	21.9 (9.3 to 40.0)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 to Visit 9)

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End point title

Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 to Visit 9) ^[22]

End point description

An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An MAE was defined as a non-serious AE (AE other than SAE) that resulted in an evaluation at a medical facility. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.

End point type

Primary

End point timeframe

From Visit 7 (time of booster vaccination, Month 48) to Visit 9 (6 months after booster vaccination, Month 54)

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)
SAE	1.7 (0.0 to 9.1)	1.1 (0.0 to 5.9)	3.1 (0.4 to 10.8)	1.9 (0.0 to 9.9)	0.0 (0.0 to 10.9)
MAE	32.2 (20.6 to 45.6)	15.2 (8.6 to 24.2)	15.6 (7.8 to 26.9)	11.1 (4.2 to 22.6)	25.0 (11.5 to 43.4)

No statistical analyses for this end point

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition;(NDCMC) From the 6-Month Safety Telephone call in the Primary Study Through 48 Months After the Last Dose in the Primary Study (Visit 6 in Stage 1)

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End point title

Percentage of Subjects With Newly Diagnosed Chronic Medical Condition;(NDCMC) From the 6-Month Safety Telephone call in the Primary Study Through 48 Months After the Last Dose in the Primary Study (Visit 6 in Stage 1) ^[23]

End point description

End point type

Primary

End point timeframe

Visit 1 of B1971033 (6-month safety telephone call after last dose in primary study) to Visit 6 of B1971033 (6 months after last primary dose to 48 months after last primary dose in primary study)

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	Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	70	101	277	116	86	46
Units: percentage of subjects
number (confidence interval 95%)	5.7 (1.6 to 14.0)	5.0 (1.6 to 11.2)	2.2 (0.8 to 4.7)	2.6 (0.5 to 7.4)	2.3 (0.3 to 8.1)	2.2 (0.1 to 11.5)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 12 Months After Booster Vaccination (Visit 8 to Visit 10)

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End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 12 Months After Booster Vaccination (Visit 8 to Visit 10) ^[24]

End point description

End point type

Primary

End point timeframe

From Visit 8 (1 month after booster vaccination, Month 49) to Visit 10 (12 months after booster vaccination, Month 60)

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)	1.7 (0.0 to 9.1)	2.2 (0.3 to 7.6)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Stage Vaccination Through 12 Months After Booster Vaccination (Visit 7 to Visit 10)

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End point title

Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Stage Vaccination Through 12 Months After Booster Vaccination (Visit 7 to Visit 10) ^[25]

End point description

End point type

Primary

End point timeframe

From Visit 7 (time of booster vaccination, Month 48) to Visit 10 (12 months after booster vaccination, Month 60)

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)	1.7 (0.0 to 9.1)	2.2 (0.3 to 7.6)	0.0 (0.0 to 5.6)	0.0 (0.0 to 6.6)	0.0 (0.0 to 10.9)

No statistical analyses for this end point

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 26 Months After Booster Vaccination (Visit 8 to Visit 11)

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End point title

Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 26 Months After Booster Vaccination (Visit 8 to Visit 11) ^[26]

End point description

An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available. Here, “Overall number of subjects analyzed" signifies those subjects who were evaluable for this endpoint. Subjects who received bivalent rLP2086 in primary study B1971012 on a 0-, 2-, and 6-month or a 0- and 6-month vaccination schedule were eligible to be follow up for 26 months after booster vaccination.

End point type

Primary

End point timeframe

From Visit 8 (1 month after booster vaccination, Month 49) to Visit 11 (26 months after booster vaccination, Month 74)

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	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	49	37
Units: percentage of subjects
number (confidence interval 95%)	0.0 (0.0 to 7.3)	5.4 (0.7 to 18.2)

No statistical analyses for this end point

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Vaccine Through 26 Months After Booster Vaccination (Visit 7 to Visit 11)

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End point title

Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Vaccine Through 26 Months After Booster Vaccination (Visit 7 to Visit 11) ^[27]

End point description

An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available. Subjects who received bivalent rLP2086 in primary study B1971012 on a 0-, 2-, and 6-month or a 0- and 6-month vaccination schedule were eligible to be follow up for 26 months after booster vaccination. Here, “Overall number of subjects analyzed" signifies those subjects who were evaluable for this endpoint.

End point type

Primary

End point timeframe

From Visit 7 (time of booster vaccination, Month 48) to Visit 11 (26 months after booster vaccination, Month 74)

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	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
Number of subjects analysed	49	37
Units: percentage of subjects
number (confidence interval 95%)	0.0 (0.0 to 7.3)	5.4 (0.7 to 18.2)

No statistical analyses for this end point

Primary: Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Booster Vaccination

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End point title

Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Booster Vaccination ^[28]

End point description

Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.

End point type

Primary

End point timeframe

within 30 minutes after Booster Vaccination in Month 48

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: percentage of subjects
number (confidence interval 95%)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)

No statistical analyses for this end point

Primary: Number of Days Subjects Missed Work or School Due to AE From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 Through Visit 9)

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End point title

Number of Days Subjects Missed Work or School Due to AE From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 Through Visit 9) ^[29]

End point description

An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Number of days subjects missed work or school due to AE occurred following booster vaccination were reported here. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.

End point type

Primary

End point timeframe

From Visit 7 (time of booster vaccination, Month 48) Through Visit 9 (6 months after booster vaccination, Month 54)

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	Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Group 4: rLP2086 (0-and 6-Month Schedule)	Group 5: rLP2086 (0- and 2-Month Schedule)	Group 6: rLP2086 (0- and 4-Month Schedule)
Number of subjects analysed	59	92	64	54	32
Units: days	12	8	8	3	6

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs and Non SAEs: Visit 7 (Booster vaccination, Month 48) to Visit 11 (Month 74) [26 months]. Local reactions and systemic events: Recorded by subjects in e-diary from Day 1 to Day 7 after booster vaccination in Month 48.

Adverse event reporting additional description

AEs were reported for those subjects who had received the booster vaccination (Bivalent rLP2086) and for whom safety information was available for disclosure.SAEs were not collected for stage 1 of the study.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Stage 2, Group2: rLP2086 (0-, 1-, and 6-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

Reporting group title

Stage 2, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

Reporting group title

Stage 2, Group 4: rLP2086 (0-and 6-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

Reporting group title

Stage 2, Group 5: rLP2086 (0- and 2-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

Reporting group title

Stage 2, Group 6: rLP2086 (0- and 4-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

Reporting group title

Stage 1, Group 1:MCV4+Tdap+Saline (0-, 2-, 6-Month Schedule)

Reporting group description

Subjects received MCV4+Tdap+Saline at Month 0, Saline only at Month 2 and 6 schedule in primary study B1971015 and were followed up for 48 months during the stage 1 of this study.

Reporting group title

Stage 1, Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

Reporting group title

Stage 1, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study.

Reporting group title

Stage 1, Group 4: rLP2086 (0-and 6-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

Reporting group title

Stage 1, Group 5: rLP2086 (0- and 2-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

Reporting group title

Stage 1, Group 6: rLP2086 (0- and 4-Month Schedule)

Reporting group description

Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

Serious adverse events	Stage 2, Group2: rLP2086 (0-, 1-, and 6-Month Schedule)	Stage 2, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Stage 2, Group 4: rLP2086 (0-and 6-Month Schedule)	Stage 2, Group 5: rLP2086 (0- and 2-Month Schedule)	Stage 2, Group 6: rLP2086 (0- and 4-Month Schedule)	Stage 1, Group 1:MCV4+Tdap+Saline (0-, 2-, 6-Month Schedule)	Stage 1, Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Stage 1, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Stage 1, Group 4: rLP2086 (0-and 6-Month Schedule)	Stage 1, Group 5: rLP2086 (0- and 2-Month Schedule)	Stage 1, Group 6: rLP2086 (0- and 4-Month Schedule)
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 59 (1.69%)	1 / 92 (1.09%)	2 / 64 (3.13%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Meniscus injury
Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Influenza like illness
Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	1 / 64 (1.56%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pyelonephritis
Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	1 / 64 (1.56%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Stage 2, Group2: rLP2086 (0-, 1-, and 6-Month Schedule)	Stage 2, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Stage 2, Group 4: rLP2086 (0-and 6-Month Schedule)	Stage 2, Group 5: rLP2086 (0- and 2-Month Schedule)	Stage 2, Group 6: rLP2086 (0- and 4-Month Schedule)	Stage 1, Group 1:MCV4+Tdap+Saline (0-, 2-, 6-Month Schedule)	Stage 1, Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)	Stage 1, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)	Stage 1, Group 4: rLP2086 (0-and 6-Month Schedule)	Stage 1, Group 5: rLP2086 (0- and 2-Month Schedule)	Stage 1, Group 6: rLP2086 (0- and 4-Month Schedule)
Total subjects affected by non serious adverse events
subjects affected / exposed	56 / 59 (94.92%)	90 / 92 (97.83%)	62 / 64 (96.88%)	53 / 54 (98.15%)	31 / 32 (96.88%)	4 / 70 (5.71%)	0 / 101 (0.00%)	1 / 277 (0.36%)	0 / 116 (0.00%)	2 / 86 (2.33%)	1 / 46 (2.17%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Hypotension
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Peripheral artery thrombosis
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Influenza like illness
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Withdrawal syndrome
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Chills
alternative assessment type: Systematic
subjects affected / exposed	14 / 59 (23.73%)	29 / 92 (31.52%)	13 / 64 (20.31%)	10 / 54 (18.52%)	9 / 32 (28.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	14	29	13	10	9	0	0	0	0	0	0
Fatigue
alternative assessment type: Systematic
subjects affected / exposed	37 / 59 (62.71%)	56 / 92 (60.87%)	40 / 64 (62.50%)	28 / 54 (51.85%)	21 / 32 (65.63%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	37	56	40	28	21	0	0	0	0	0	0
Injection site erythema (redness)
alternative assessment type: Systematic
subjects affected / exposed	12 / 59 (20.34%)	19 / 92 (20.65%)	13 / 64 (20.31%)	15 / 54 (27.78%)	2 / 32 (6.25%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	12	19	13	15	2	0	0	0	0	0	0
Injection site pain (tenderness at injection site)
alternative assessment type: Systematic
subjects affected / exposed	54 / 59 (91.53%)	86 / 92 (93.48%)	57 / 64 (89.06%)	48 / 54 (88.89%)	27 / 32 (84.38%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	54	86	57	48	27	0	0	0	0	0	0
Injection site swelling (swelling)
alternative assessment type: Systematic
subjects affected / exposed	11 / 59 (18.64%)	19 / 92 (20.65%)	11 / 64 (17.19%)	8 / 54 (14.81%)	3 / 32 (9.38%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	11	19	11	8	3	0	0	0	0	0	0
Pyrexia (fever)
alternative assessment type: Systematic
subjects affected / exposed	3 / 59 (5.08%)	1 / 92 (1.09%)	3 / 64 (4.69%)	1 / 54 (1.85%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	3	1	3	1	1	0	0	0	0	0	0
Immune system disorders
Mite allergy
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Seasonal allergy
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	1 / 86 (1.16%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Testicular pain
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Gastrointestinal somatic symptom disorder
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Generalised anxiety disorder
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Persistent depressive disorder
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Investigations
Borrelia test positive
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	1 / 59 (1.69%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0
Fall
subjects affected / exposed	1 / 59 (1.69%)	1 / 92 (1.09%)	0 / 64 (0.00%)	2 / 54 (3.70%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	1	0	2	0	0	0	0	0	0	0
Head injury
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	1 / 64 (1.56%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0
Joint injury
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	1 / 64 (1.56%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0
Laceration
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Ligament sprain
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Limb injury
subjects affected / exposed	1 / 59 (1.69%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	1	0	0	1	0	0	0	0	0	0
Muscle injury
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Muscle strain
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0
Neck injury
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Road traffic accident
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Vasoplegia syndrome
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Wrist fracture
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	2 / 54 (3.70%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	2	0	0	0	0	0	0	0
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Cardiac arrest
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
Brain injury
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Disturbance in attention
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0
Migraine
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	1 / 54 (1.85%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0
Syncope
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Headache
alternative assessment type: Systematic
subjects affected / exposed	30 / 59 (50.85%)	44 / 92 (47.83%)	36 / 64 (56.25%)	26 / 54 (48.15%)	12 / 32 (37.50%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	30	44	36	26	12	0	0	0	0	0	0
Orthostatic intolerance
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	1 / 70 (1.43%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Eye disorders
Myopia
subjects affected / exposed	2 / 59 (3.39%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	0	0
Hypermetropia
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	1 / 46 (2.17%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Gastrointestinal disorders
Constipation
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Gastric ulcer
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Impaired gastric emptying
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Oesophageal varices haemorrhage
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Diarrhoea
alternative assessment type: Systematic
subjects affected / exposed	6 / 59 (10.17%)	12 / 92 (13.04%)	3 / 64 (4.69%)	3 / 54 (5.56%)	6 / 32 (18.75%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	12	3	3	6	0	0	0	0	0	0
Vomiting
alternative assessment type: Systematic
subjects affected / exposed	1 / 59 (1.69%)	3 / 92 (3.26%)	2 / 64 (3.13%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	3	2	1	0	0	0	0	0	0	0
Irritable bowel syndrome
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	1 / 70 (1.43%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Eczema
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Psoriasis
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	1 / 64 (1.56%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	1 / 64 (1.56%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Endocrine disorders
Autoimmune thyroiditis
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	1 / 70 (1.43%)	0 / 101 (0.00%)	1 / 277 (0.36%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 59 (1.69%)	1 / 92 (1.09%)	0 / 64 (0.00%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0	0	0	0
Arthralgia
alternative assessment type: Systematic
subjects affected / exposed	7 / 59 (11.86%)	15 / 92 (16.30%)	9 / 64 (14.06%)	10 / 54 (18.52%)	7 / 32 (21.88%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	7	15	9	10	7	0	0	0	0	0	0
Myalgia
alternative assessment type: Systematic
subjects affected / exposed	13 / 59 (22.03%)	27 / 92 (29.35%)	12 / 64 (18.75%)	13 / 54 (24.07%)	5 / 32 (15.63%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	13	27	12	13	5	0	0	0	0	0	0
Osteochondrosis
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	1 / 70 (1.43%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Infections and infestations
Body tinea
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Bronchitis
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	1 / 64 (1.56%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Cervicitis
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Chlamydial infection
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Cystitis
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	1 / 86 (1.16%)	0 / 46 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	1	0
Gastroenteritis
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	1 / 64 (1.56%)	1 / 54 (1.85%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	1	1	1	0	0	0	0	0	0
Genitourinary chlamydia infection
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Impetigo
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	1 / 64 (1.56%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0
Infection
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0	0	0
Laryngitis
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Lower respiratory tract infection viral
subjects affected / exposed	0 / 59 (0.00%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	3 / 59 (5.08%)	2 / 92 (2.17%)	5 / 64 (7.81%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	3	2	5	1	0	0	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Otitis media acute
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	3 / 59 (5.08%)	0 / 92 (0.00%)	1 / 64 (1.56%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	3	0	1	0	1	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Rhinitis
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Tonsillitis
subjects affected / exposed	1 / 59 (1.69%)	1 / 92 (1.09%)	2 / 64 (3.13%)	0 / 54 (0.00%)	2 / 32 (6.25%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	2	2	0	2	0	0	0	0	0	0
Tooth infection
subjects affected / exposed	0 / 59 (0.00%)	0 / 92 (0.00%)	0 / 64 (0.00%)	1 / 54 (1.85%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Tracheitis
subjects affected / exposed	3 / 59 (5.08%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	3	0	0	0	1	0	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	1 / 59 (1.69%)	2 / 92 (2.17%)	0 / 64 (0.00%)	0 / 54 (0.00%)	1 / 32 (3.13%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	2	0	0	1	0	0	0	0	0	0
Infectious mononucleosis
subjects affected / exposed	1 / 59 (1.69%)	1 / 92 (1.09%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Electrolyte imbalance
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Hypomagnesaemia
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Vitamin K deficiency
subjects affected / exposed	1 / 59 (1.69%)	0 / 92 (0.00%)	0 / 64 (0.00%)	0 / 54 (0.00%)	0 / 32 (0.00%)	0 / 70 (0.00%)	0 / 101 (0.00%)	0 / 277 (0.00%)	0 / 116 (0.00%)	0 / 86 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

21 Mar 2012

Addition of the benefit-risk assessment in the protocol.

19 Dec 2013

Updation of requirement to report serious adverse events back to the primary studies after the active reporting phase, Addition of Section 7.1.2 on the Luminex assay for antigen detection for MCV4, collection of newly diagnosed chronic medical conditions.

08 Jan 2015

Addition of a booster dose (booster stage), primary safety objective/endpoints describing the safety profile of bivalent rLP2086 booster vaccination. Updation of safety reporting requirements to reflect receipt of the booster dose.

18 Apr 2017

Extension of booster stage follow-up duration from 12 months to 26 months, Addition of an additional blood draw visit (Visit 11) to assess immune response 26 months after the booster dose, Updation of the primary and objectives and corresponding endpoint relating to immunogenicity assessment for the booster stage follow-up at 26 months, primary safety endpoint relating to the booster stage follow-up at 26 months. Addition of Visit 11 to the adverse event, Visit 11 to data analysis for immunogenicity and safety endpoints.

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 Study to Assess the Persistence of hSBA Response up to 48 Months After Completion of a Primary Series of Bivalent rLP2086, and the Safety, Tolerability, and Immunogenicity of a Booster Dose of Bivalent rLP2086

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 12 (Visit 2) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 12 (Visit 2) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 18 (Visit 3) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 18 (Visit 3) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 24 (Visit 4) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 24 (Visit 4) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 36 (Visit 5) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 36 (Visit 5) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 48 (Visit 6) After Primary Vaccinations

Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 48 (Visit 6) After Primary Vaccinations

Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After Last Vaccination in Primary Study

Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After Last Vaccination in Primary Study

Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level >= Lower Limit of Quantitation for Each of the 4 Primary Strains Before Booster Vaccination (48 Months After Last Vaccination in Primary Study [Visit 6])

Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level >= Lower Limit of Quantitation for Each of the 4 Primary Strains Before Booster Vaccination (48 Months After Last Vaccination in Primary Study [Visit 6])

Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After the Booster Vaccination (Visit 8)

Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After the Booster Vaccination (Visit 8)

Primary: Percentage of Subjects Achieving hSBATiter Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 12 Months After the Booster Vaccination(Visit 10)

Primary: Percentage of Subjects Achieving hSBATiter Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 12 Months After the Booster Vaccination(Visit 10)

Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to(>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 26 Months After the Booster Vaccination(Visit 11)

Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to(>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 26 Months After the Booster Vaccination(Visit 11)

Primary: Percentage of Subjects Reporting Local Reactions Within 7 Days After Booster Vaccination

Primary: Percentage of Subjects Reporting Local Reactions Within 7 Days After Booster Vaccination

Primary: Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination

Primary: Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Medically Attended Adverse Event (MAE) From Booster Vaccination Phase (Visit 7 to Visit 8)

Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Medically Attended Adverse Event (MAE) From Booster Vaccination Phase (Visit 7 to Visit 8)

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Follow-Up Phase (Visit 8 to Visit 9)

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Follow-Up Phase (Visit 8 to Visit 9)

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 to Visit 9)

Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 to Visit 9)

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition;(NDCMC) From the 6-Month Safety Telephone call in the Primary Study Through 48 Months After the Last Dose in the Primary Study (Visit 6 in Stage 1)

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition;(NDCMC) From the 6-Month Safety Telephone call in the Primary Study Through 48 Months After the Last Dose in the Primary Study (Visit 6 in Stage 1)

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 12 Months After Booster Vaccination (Visit 8 to Visit 10)

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 12 Months After Booster Vaccination (Visit 8 to Visit 10)

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Stage Vaccination Through 12 Months After Booster Vaccination (Visit 7 to Visit 10)

Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Stage Vaccination Through 12 Months After Booster Vaccination (Visit 7 to Visit 10)

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 26 Months After Booster Vaccination (Visit 8 to Visit 11)

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 26 Months After Booster Vaccination (Visit 8 to Visit 11)

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Vaccine Through 26 Months After Booster Vaccination (Visit 7 to Visit 11)

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Vaccine Through 26 Months After Booster Vaccination (Visit 7 to Visit 11)

Primary: Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Booster Vaccination

Primary: Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Booster Vaccination

Primary: Number of Days Subjects Missed Work or School Due to AE From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 Through Visit 9)

Primary: Number of Days Subjects Missed Work or School Due to AE From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 Through Visit 9)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3 Study to Assess the Persistence of hSBA Response up to 48 Months After Completion of a Primary Series of Bivalent rLP2086, and the Safety, Tolerability, and Immunogenicity of a Booster Dose of Bivalent rLP2086