A Study to Evaluate the Effects of Ocrelizumab on Immune Responses In Participants With Relapsing Forms of Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT02545868
• Recruitment Status: Completed
• First Posted: September 10, 2015
• Results First Posted: June 6, 2018
• Last Update Posted: April 28, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care
• Condition: Multiple Sclerosis, Relapsing-Remitting
• Interventions: Biological: 23-PPV; Biological: 13-PCV Booster; Biological: Influenza Vaccine; Biological: KLH; Drug: OCR; Biological: TT Vaccine
• Enrollment: 102

Participant Flow

Recruitment Details	The study recruited participants with relapsing forms of multiple sclerosis in 2 countries from 27 October 2015 to 14 February 2017.
Pre-assignment Details	A total of 122 participants were screened of which 102 participants were randomized.

Arm/Group Title	Group A1	Group A2	Group B
Arm/Group Description	Participants received dual infusion of ocrelizumab (OCR) 300 milligrams (mg) on Day 1 and then on Day 15, and then participants further received immunization course: tetanus toxoid (TT) containing adsorbed vaccine, 23-valent pneumococcal polysaccharide vaccine (23-PPV) boosted with 13-valent pneumococcal conjugate vaccine (13-PCV), and repeated administration with keyhole limpet hemocyanin (KLH) at 12 weeks post-OCR treatment until Week 24. Participants who completed the 24-week immunization study period had the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks.	Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24. Participants who completed the 24-week immunization study period had the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period. Participants who completed the 12-week immunization study period had the option to receive two single infusions of OCR 300 mg, on Day 84 and Day 98, and subsequent single infusions (600 mg OCR) at intervals of 24 weeks.
Period Title: Immunization Study Period (ISP)
Started	33	35	34
Completed	33	35	34
Not Completed	0	0	0
Period Title: Optional Ocrelizumab Ext (OOE) Period
Started	33	35	34
Completed	0	0	0
Not Completed	33	35	34
Reason Not Completed
OOE period ongoing	33	35	34

Baseline Characteristics

Arm/Group Title		Group A1	Group A2	Group B	Total
Arm/Group Description		Participants received dual infusion of ocrelizumab (OCR) 300 milligrams (mg) on Day 1 and then on Day 15, and then participants further received immunization course: tetanus toxoid (TT) containing adsorbed vaccine, 23-valent pneumococcal polysaccharide vaccine (23-PPV) boosted with 13-valent pneumococcal conjugate vaccine (13-PCV), and repeated administration with keyhole limpet hemocyanin (KLH) at 12 weeks post-OCR treatment until Week 24.	Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period. Participants who completed the 12-week immunization study period had the option to receive two single infusions of OCR 300 mg, on Day 84 and Day 98, and subsequent single infusions (600 mg OCR) at intervals of 24 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		33	35	34	102
Baseline Analysis Population Description		Observed Cases (OC) Population was defined as all randomized participants who completed the ISP.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	33 participants	35 participants	34 participants	102 participants
		40.1 (8.0)	39.3 (9.7)	41.4 (7.9)	40.3 (8.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants	35 participants	34 participants	102 participants
	Female	21 63.6%	24 68.6%	27 79.4%	72 70.6%
	Male	12 36.4%	11 31.4%	7 20.6%	30 29.4%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Ethnicity	Number Analyzed	33 participants	35 participants	34 participants	102 participants
	Hispanic or Latino	2 6.1%	2 5.7%	2 5.9%	6 5.9%
	Not Hispanic or Latino	29 87.9%	30 85.7%	32 94.1%	91 89.2%
	Not reported	1 3.0%	1 2.9%	0 0.0%	2 2.0%
	Unknown	1 3.0%	2 5.7%	0 0.0%	3 2.9%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	33 participants	35 participants	34 participants	102 participants
	Asian	1 3.0%	0 0.0%	2 5.9%	3 2.9%
	Black or African American	0 0.0%	3 8.6%	2 5.9%	5 4.9%
	White	32 97.0%	32 91.4%	30 88.2%	94 92.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Positive Response to TT Vaccine Measured 8 Weeks After TT Vaccine
Description	For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 8 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 8 weeks after vaccination compared with pre-vaccination levels.
Time Frame	8 weeks after TT vaccine

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of ocrelizumab (OCR) 300 milligrams (mg) on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: tetanus toxoid (TT) containing adsorbed vaccine, 23-valent pneumococcal polysaccharide vaccine (23-PPV) and repeated administration with keyhole limpet hemocyanin (KLH). In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Measure Type: Number; Unit of Measure: percentage of participants
	23.9	54.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Difference in positive response, Group A minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	normal distribution approximation
	Estimated Value	-30.7
	Confidence Interval	(2-Sided) 95%; -50.5 to -10.8
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants With Positive Response to TT Vaccine Measured 4 Weeks After TT Vaccine
Description	For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.
Time Frame	4 weeks after TT vaccine

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Measure Type: Number; Unit of Measure: percentage of participants
	24.2	60.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Difference in positive response, Group A minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	normal distribution approximation
	Estimated Value	-36.4
	Confidence Interval	(2-Sided) 95%; -56.0 to -16.7
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants With Tetanus Antibody Titer >/=0.2 IU/mL or 2-Fold Increase in Tetanus Antibody Titers
Description	For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 2-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.
Time Frame	4 weeks after TT vaccine

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Measure Type: Number; Unit of Measure: percentage of participants
	40.9	87.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Difference in positive response, Group A minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	normal distribution approximation
	Estimated Value	-47.0
	Confidence Interval	(2-Sided) 95%; -63.2 to -30.7
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Mean Levels of Anti-Tetanus Antibody
Description	Anti-tetanus antibody levels were assessed by enzyme-linked immunosorbent assay (ELISA).
Time Frame	Immediately prior to and at 4 and 8 weeks after TT vaccine

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title		Group A (A1 + A2)	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		68	34
Geometric Mean (95% Confidence Interval); Unit of Measure: IU/mL
Pre-Vaccination	Number Analyzed	67 participants	34 participants
		1.680; (1.275 to 2.214)	2.147; (1.612 to 2.859)
4 weeks after TT vaccine	Number Analyzed	67 participants	33 participants
		4.132; (3.373 to 5.061)	12.157; (9.498 to 15.560)
8 weeks after TT vaccine	Number Analyzed	68 participants	33 participants
		3.743; (3.048 to 4.596)	9.812; (7.842 to 12.277)

5. Secondary Outcome

Title	Mean Levels of Anti-KLH Antibody: Immunoglobulin (Ig) G
Description	Anti-KLH antibody levels were assessed by ELISA.
Time Frame	Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title		Group A (A1 + A2)	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		68	34
Geometric Mean (95% Confidence Interval); Unit of Measure: titer units
Immediately prior to first KLH administration	Number Analyzed	68 participants	34 participants
		274; (213 to 354)	235; (180 to 308)
4 weeks after first KLH administration	Number Analyzed	68 participants	34 participants
		384; (285 to 517)	1086; (769 to 1534)
8 weeks after first KLH administration	Number Analyzed	68 participants	34 participants
		2916; (1998 to 4253)	17737; (12441 to 25287)
12 weeks after first KLH administration	Number Analyzed	66 participants	34 participants
		5298; (3794 to 7397)	60270; (43557 to 83396)

6. Secondary Outcome

Title	Mean Levels of Anti-KLH Antibody: Ig M
Description	Anti-KLH antibody levels were assessed by ELISA.
Time Frame	Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title		Group A (A1 + A2)	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		68	34
Geometric Mean (95% Confidence Interval); Unit of Measure: titer units
Immediately prior to first KLH administration	Number Analyzed	67 participants	34 participants
		100; (82 to 122)	130; (101 to 168)
4 weeks after first KLH administration	Number Analyzed	67 participants	34 participants
		124; (100 to 155)	217; (158 to 298)
8 weeks after first KLH administration	Number Analyzed	68 participants	34 participants
		361; (273 to 478)	1086; (797 to 1481)
12 weeks after first KLH administration	Number Analyzed	66 participants	34 participants
		372; (286 to 483)	1883; (1405 to 2524)

7. Secondary Outcome

Title	Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 23-PPV
Description	Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or greater than (>) 1 microgram per milliliter (mcg/mL) rise compared with pre-vaccination levels.
Time Frame	4 weeks after 23-PPV

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title		Group A (A1 + A2)	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		68	34
Measure Type: Number; Unit of Measure: percentage of participants
Serotype 1	Number Analyzed	67 participants	34 participants
		49.3	100.0
Serotype 2	Number Analyzed	67 participants	34 participants
		53.7	97.1
Serotype 3	Number Analyzed	67 participants	34 participants
		34.3	82.4
Serotype 4	Number Analyzed	67 participants	34 participants
		28.4	91.2
Serotype 5	Number Analyzed	67 participants	34 participants
		40.3	94.1
Serotype 6B	Number Analyzed	67 participants	34 participants
		47.8	85.3
Serotype 7F	Number Analyzed	67 participants	34 participants
		32.8	91.2
Serotype 8	Number Analyzed	67 participants	34 participants
		64.2	97.1
Serotype 9N	Number Analyzed	67 participants	34 participants
		41.8	88.2
Serotype 9V	Number Analyzed	67 participants	34 participants
		50.7	91.2
Serotype 10A	Number Analyzed	67 participants	34 participants
		28.4	91.2
Serotype 11A	Number Analyzed	67 participants	34 participants
		29.9	82.4
Serotype 12F	Number Analyzed	67 participants	34 participants
		20.9	76.5
Serotype 14	Number Analyzed	67 participants	34 participants
		62.7	88.2
Serotype 15B	Number Analyzed	67 participants	34 participants
		40.3	88.2
Serotype 17F	Number Analyzed	67 participants	34 participants
		31.3	88.2
Serotype 18C	Number Analyzed	67 participants	34 participants
		38.8	91.2
Serotype 19A	Number Analyzed	67 participants	34 participants
		41.8	88.2
Serotype 19F	Number Analyzed	67 participants	34 participants
		32.8	85.3
Serotype 20	Number Analyzed	67 participants	34 participants
		20.9	82.4
Serotype 22F	Number Analyzed	67 participants	34 participants
		34.3	91.2
Serotype 23F	Number Analyzed	67 participants	34 participants
		43.3	76.5
Serotype 33F	Number Analyzed	67 participants	34 participants
		46.3	94.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 1
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-50.7
	Confidence Interval	(2-Sided) 95%; -62.7 to -38.8
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 2
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-43.3
	Confidence Interval	(2-Sided) 95%; -56.5 to -30.1
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 3
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-48.0
	Confidence Interval	(2-Sided) 95%; -65.2 to -30.9
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 4
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-62.8
	Confidence Interval	(2-Sided) 95%; -77.2 to -48.4
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 5
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-53.8
	Confidence Interval	(2-Sided) 95%; -68.0 to -39.7
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 6B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-37.5
	Confidence Interval	(2-Sided) 95%; -54.4 to -20.7
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 7F
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-58.3
	Confidence Interval	(2-Sided) 95%; -73.1 to -43.6
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 8
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-32.9
	Confidence Interval	(2-Sided) 95%; -45.7 to -20.1
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 9N
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-46.4
	Confidence Interval	(2-Sided) 95%; -62.5 to -30.4
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 9V
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-40.4
	Confidence Interval	(2-Sided) 95%; -55.7 to -25.1
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 10A
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-62.8
	Confidence Interval	(2-Sided) 95%; -77.2 to -48.4
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 11A
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.5
	Confidence Interval	(2-Sided) 95%; -69.4 to -35.6
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 12F
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-55.6
	Confidence Interval	(2-Sided) 95%; -72.8 to -38.3
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 14
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-25.5
	Confidence Interval	(2-Sided) 95%; -41.4 to -9.7
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 15B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-47.9
	Confidence Interval	(2-Sided) 95%; -63.9 to -32.0
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 17F
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-56.9
	Confidence Interval	(2-Sided) 95%; -72.4 to -41.4
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 18C
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.4
	Confidence Interval	(2-Sided) 95%; -67.4 to -37.3
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 19A
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-46.4
	Confidence Interval	(2-Sided) 95%; -62.5 to -30.4
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 19F
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.5
	Confidence Interval	(2-Sided) 95%; -68.8 to -36.1
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 20
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-61.5
	Confidence Interval	(2-Sided) 95%; -77.5 to -45.4
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 22F
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-56.8
	Confidence Interval	(2-Sided) 95%; -71.7 to -42.0
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 23F
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-33.2
	Confidence Interval	(2-Sided) 95%; -51.7 to -14.6
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	Serotype 33F
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-47.8
	Confidence Interval	(2-Sided) 95%; -62.2 to -33.5
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Percentage of Participants With Positive Response Against >/=2 Pneumococcal Serotypes
Description	Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.
Time Frame	4 weeks after 23-PPV

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Measure Type: Number; Unit of Measure: percentage of participants
	86.6	100.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-13.4
	Confidence Interval	(2-Sided) 95%; -21.6 to -5.3
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Participants With Positive Response Against >/=12 Pneumococcal Serotypes
Description	Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.
Time Frame	4 weeks after 23-PPV

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Measure Type: Number; Unit of Measure: percentage of participants
	37.3	97.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A (A1 + A2), Group B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-59.7
	Confidence Interval	(2-Sided) 95%; -72.6 to -46.8
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Mean Levels of Anti-Pneumococcal Antibody
Description	Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).
Time Frame	Immediately prior to and 4 weeks after 23-PPV

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title		Group A (A1 + A2)	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		68	34
Geometric Mean (95% Confidence Interval); Unit of Measure: mcg/mL
Immediately prior to 23-PPV: Serotype : 1	Number Analyzed	67 participants	34 participants
		0.94; (0.71 to 1.26)	1.02; (0.71 to 1.46)
Immediately prior to 23-PPV: Serotype : 2	Number Analyzed	67 participants	34 participants
		1.12; (0.85 to 1.47)	1.25; (0.93 to 1.69)
Immediately prior to 23-PPV: Serotype : 3	Number Analyzed	67 participants	34 participants
		1.10; (0.81 to 1.50)	0.95; (0.66 to 1.36)
Immediately prior to 23-PPV: Serotype : 4	Number Analyzed	67 participants	34 participants
		0.68; (0.41 to 1.13)	0.59; (0.40 to 0.88)
Immediately prior to 23-PPV: Serotype : 5	Number Analyzed	67 participants	34 participants
		0.96; (0.72 to 1.27)	1.31; (0.91 to 1.89)
Immediately prior to 23-PPV: Serotype : 6B	Number Analyzed	67 participants	34 participants
		0.84; (0.63 to 1.11)	0.92; (0.60 to 1.39)
Immediately prior to 23-PPV: Serotype : 7F	Number Analyzed	67 participants	34 participants
		0.89; (0.72 to 1.10)	0.94; (0.70 to 1.27)
Immediately prior to 23-PPV: Serotype : 8	Number Analyzed	67 participants	34 participants
		0.92; (0.68 to 1.23)	0.91; (0.59 to 1.38)
Immediately prior to 23-PPV: Serotype : 9N	Number Analyzed	67 participants	34 participants
		0.74; (0.55 to 1.01)	1.06; (0.68 to 1.64)
Immediately prior to 23-PPV: Serotype : 9V	Number Analyzed	67 participants	34 participants
		0.79; (0.55 to 1.13)	0.74; (0.50 to 1.11)
Immediately prior to 23-PPV: Serotype : 10A	Number Analyzed	67 participants	34 participants
		0.88; (0.66 to 1.17)	0.96; (0.73 to 1.26)
Immediately prior to 23-PPV: Serotype : 11F	Number Analyzed	67 participants	34 participants
		1.09; (0.81 to 1.45)	1.03; (0.69 to 1.52)
Immediately prior to 23-PPV: Serotype : 12F	Number Analyzed	67 participants	34 participants
		0.79; (0.46 to 1.36)	0.54; (0.35 to 0.83)
Immediately prior to 23-PPV: Serotype : 14	Number Analyzed	67 participants	34 participants
		1.33; (0.97 to 1.84)	1.09; (0.71 to 1.68)
Immediately prior to 23-PPV: Serotype : 15B	Number Analyzed	67 participants	34 participants
		0.82; (0.68 to 1.00)	1.18; (0.73 to 1.92)
Immediately prior to 23-PPV: Serotype : 17F	Number Analyzed	67 participants	34 participants
		0.89; (0.70 to 1.14)	1.05; (0.75 to 1.48)
Immediately prior to 23-PPV: Serotype : 18C	Number Analyzed	67 participants	34 participants
		1.08; (0.83 to 1.41)	1.14; (0.79 to 1.64)
Immediately prior to 23-PPV: Serotype : 19A	Number Analyzed	67 participants	34 participants
		1.58; (1.14 to 2.20)	2.09; (1.26 to 3.46)
Immediately prior to 23-PPV: Serotype : 19F	Number Analyzed	67 participants	34 participants
		1.09; (0.89 to 1.35)	1.16; (0.80 to 1.67)
Immediately prior to 23-PPV: Serotype : 20	Number Analyzed	67 participants	34 participants
		1.71; (1.27 to 2.29)	1.29; (0.89 to 1.87)
Immediately prior to 23-PPV: Serotype : 22F	Number Analyzed	67 participants	34 participants
		0.73; (0.55 to 0.97)	0.82; (0.55 to 1.20)
Immediately prior to 23-PPV: Serotype : 23F	Number Analyzed	67 participants	34 participants
		0.72; (0.56 to 0.93)	0.96; (0.66 to 1.41)
Immediately prior to 23-PPV: Serotype : 33F	Number Analyzed	67 participants	34 participants
		0.96; (0.76 to 1.22)	0.67; (0.52 to 0.85)
4 weeks after 23-PPV: Serotype : 1	Number Analyzed	68 participants	34 participants
		1.31; (1.03 to 1.67)	11.58; (7.72 to 17.38)
4 weeks after 23-PPV: Serotype : 2	Number Analyzed	68 participants	34 participants
		1.79; (1.38 to 2.30)	9.41; (6.80 to 13.01)
4 weeks after 23-PPV: Serotype : 3	Number Analyzed	68 participants	34 participants
		1.57; (1.20 to 2.06)	2.76; (1.72 to 4.42)
4 weeks after 23-PPV: Serotype : 4	Number Analyzed	68 participants	34 participants
		1.54; (1.01 to 2.35)	2.02; (1.32 to 3.08)
4 weeks after 23-PPV: Serotype : 5	Number Analyzed	68 participants	34 participants
		1.25; (0.97 to 1.62)	10.16; (5.69 to 18.15)
4 weeks after 23-PPV: Serotype : 6B	Number Analyzed	68 participants	34 participants
		1.47; (1.03 to 2.10)	3.94; (2.12 to 7.33)
4 weeks after 23-PPV: Serotype : 7F	Number Analyzed	68 participants	34 participants
		1.36; (1.06 to 1.74)	4.92; (2.99 to 8.09)
4 weeks after 23-PPV: Serotype : 8	Number Analyzed	68 participants	34 participants
		1.78; (1.35 to 2.35)	9.04; (6.42 to 12.73)
4 weeks after 23-PPV: Serotype : 9N	Number Analyzed	68 participants	34 participants
		1.21; (0.89 to 1.65)	3.26; (2.02 to 5.28)
4 weeks after 23-PPV: Serotype : 9V	Number Analyzed	68 participants	34 participants
		0.94; (0.71 to 1.24)	3.84; (2.37 to 6.21)
4 weeks after 23-PPV: Serotype : 10A	Number Analyzed	68 participants	34 participants
		1.14; (0.84 to 1.55)	5.20; (3.27 to 8.28)
4 weeks after 23-PPV: Serotype : 11F	Number Analyzed	68 participants	34 participants
		1.34; (1.03 to 1.74)	4.74; (3.17 to 7.09)
4 weeks after 23-PPV: Serotype : 12F	Number Analyzed	68 participants	34 participants
		1.13; (0.68 to 1.87)	1.82; (1.11 to 2.99)
4 weeks after 23-PPV: Serotype : 14	Number Analyzed	68 participants	34 participants
		3.22; (2.29 to 4.54)	12.51; (7.50 to 20.86)
4 weeks after 23-PPV: Serotype : 15B	Number Analyzed	68 participants	34 participants
		1.57; (1.22 to 2.03)	5.60; (3.20 to 9.80)
4 weeks after 23-PPV: Serotype : 17F	Number Analyzed	68 participants	34 participants
		1.41; (1.09 to 1.84)	5.33; (3.63 to 7.82)
4 weeks after 23-PPV: Serotype : 18C	Number Analyzed	68 participants	34 participants
		1.55; (1.18 to 2.03)	7.35; (4.39 to 12.31)
4 weeks after 23-PPV: Serotype : 19A	Number Analyzed	68 participants	34 participants
		2.47; (1.71 to 3.55)	8.96; (5.43 to 14.80)
4 weeks after 23-PPV: Serotype : 19F	Number Analyzed	68 participants	34 participants
		1.57; (1.26 to 1.95)	5.09; (3.25 to 7.97)
4 weeks after 23-PPV: Serotype : 20	Number Analyzed	68 participants	34 participants
		2.03; (1.52 to 2.71)	3.74; (2.39 to 5.86)
4 weeks after 23-PPV: Serotype : 22F	Number Analyzed	68 participants	34 participants
		1.10; (0.85 to 1.42)	4.51; (2.93 to 6.95)
4 weeks after 23-PPV: Serotype : 23F	Number Analyzed	68 participants	34 participants
		1.14; (0.90 to 1.46)	2.90; (1.81 to 4.66)
4 weeks after 23-PPV: Serotype : 33F	Number Analyzed	68 participants	34 participants
		1.44; (1.12 to 1.85)	5.11; (3.25 to 8.05)

11. Secondary Outcome

Title	Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 13-PCV
Description	Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.
Time Frame	8 weeks after 23-PPV, which was 4 weeks after Group A1 participants received 13-PCV

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title		Group A1	Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV boosted with 13-PCV, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		33	35	34
Measure Type: Number; Unit of Measure: percentage of participants
Serotype 1	Number Analyzed	31 participants	34 participants	34 participants
		54.8	38.2	100.0
Serotype 2	Number Analyzed	31 participants	34 participants	34 participants
		54.8	44.1	97.1
Serotype 3	Number Analyzed	31 participants	34 participants	34 participants
		35.5	29.4	85.3
Serotype 4	Number Analyzed	31 participants	34 participants	34 participants
		32.3	23.5	88.2
Serotype 5	Number Analyzed	31 participants	34 participants	34 participants
		38.7	44.1	97.1
Serotype 6B	Number Analyzed	31 participants	34 participants	34 participants
		48.4	44.1	82.4
Serotype 7F	Number Analyzed	31 participants	34 participants	34 participants
		51.6	35.3	94.1
Serotype 8	Number Analyzed	31 participants	34 participants	34 participants
		54.8	67.6	97.1
Serotype 9N	Number Analyzed	31 participants	34 participants	34 participants
		45.2	47.1	82.4
Serotype 9V	Number Analyzed	31 participants	34 participants	34 participants
		51.6	50.0	88.2
Serotype 10A	Number Analyzed	31 participants	34 participants	34 participants
		29.0	29.4	91.2
Serotype 11A	Number Analyzed	31 participants	34 participants	34 participants
		32.3	44.1	82.4
Serotype 12F	Number Analyzed	31 participants	34 participants	34 participants
		22.6	20.6	79.4
Serotype 14	Number Analyzed	31 participants	34 participants	34 participants
		64.5	67.6	85.3
Serotype 15B	Number Analyzed	31 participants	34 participants	34 participants
		35.5	38.2	88.2
Serotype 17F	Number Analyzed	31 participants	34 participants	34 participants
		41.9	44.1	88.2
Serotype 18C	Number Analyzed	31 participants	34 participants	34 participants
		51.6	32.4	94.1
Serotype 19A	Number Analyzed	31 participants	34 participants	34 participants
		58.1	35.3	88.2
Serotype 19F	Number Analyzed	31 participants	34 participants	34 participants
		41.9	29.4	88.2
Serotype 20	Number Analyzed	31 participants	34 participants	34 participants
		25.8	14.7	85.3
Serotype 22F	Number Analyzed	31 participants	34 participants	34 participants
		38.7	23.5	91.2
Serotype 23F	Number Analyzed	31 participants	34 participants	34 participants
		48.4	29.4	76.5
Serotype 33F	Number Analyzed	31 participants	34 participants	34 participants
		45.2	44.1	94.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 1- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-45.2
	Confidence Interval	(2-Sided) 95%; -62.7 to -27.6
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 2- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-42.2
	Confidence Interval	(2-Sided) 95%; -60.6 to -23.8
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 3- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-49.8
	Confidence Interval	(2-Sided) 95%; -70.4 to -29.2
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 4- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-56.0
	Confidence Interval	(2-Sided) 95%; -75.7 to -36.3
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 5- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-58.3
	Confidence Interval	(2-Sided) 95%; -76.4 to -40.3
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 6B- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-34.0
	Confidence Interval	(2-Sided) 95%; -55.7 to -12.2
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 7F- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-42.5
	Confidence Interval	(2-Sided) 95%; -61.8 to -23.2
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 8- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-42.2
	Confidence Interval	(2-Sided) 95%; -60.6 to -23.8
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 9N- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-37.2
	Confidence Interval	(2-Sided) 95%; -58.9 to -15.5
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 9V- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-36.6
	Confidence Interval	(2-Sided) 95%; -57.3 to -16.0
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 10A- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-62.1
	Confidence Interval	(2-Sided) 95%; -80.8 to -43.5
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 11A- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-50.1
	Confidence Interval	(2-Sided) 95%; -71.0 to -29.2
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 12F- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-56.8
	Confidence Interval	(2-Sided) 95%; -76.9 to -36.8
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 14- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-20.8
	Confidence Interval	(2-Sided) 95%; -41.4 to -0.2
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 15B- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.8
	Confidence Interval	(2-Sided) 95%; -72.8 to -32.7
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 17F- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-46.3
	Confidence Interval	(2-Sided) 95%; -66.8 to -25.8
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 18C- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-42.5
	Confidence Interval	(2-Sided) 95%; -61.8 to -23.2
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 19A- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-30.2
	Confidence Interval	(2-Sided) 95%; -50.6 to -9.7
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 19F- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-46.3
	Confidence Interval	(2-Sided) 95%; -66.8 to -25.8
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 20- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-59.5
	Confidence Interval	(2-Sided) 95%; -79.0 to -40.0
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 22F- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.5
	Confidence Interval	(2-Sided) 95%; -72.1 to -32.8
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 23F- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-28.1
	Confidence Interval	(2-Sided) 95%; -50.7 to -5.4
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Group A1, Group B
	Comments	Serotype 33F- Difference in positive response, Group A1 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-49.0
	Confidence Interval	(2-Sided) 95%; -68.2 to -29.7
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 1- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-61.8
	Confidence Interval	(2-Sided) 95%; -78.1 to -45.4
	Estimation Comments	[Not Specified]

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 2- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.9
	Confidence Interval	(2-Sided) 95%; -70.6 to -35.3
	Estimation Comments	[Not Specified]

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 3- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-55.9
	Confidence Interval	(2-Sided) 95%; -75.3 to -36.5
	Estimation Comments	[Not Specified]

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 4- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-64.7
	Confidence Interval	(2-Sided) 95%; -82.6 to -46.8
	Estimation Comments	[Not Specified]

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 5- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.9
	Confidence Interval	(2-Sided) 95%; -70.6 to -35.3
	Estimation Comments	[Not Specified]

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 6B- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-38.2
	Confidence Interval	(2-Sided) 95%; -59.3 to -17.2
	Estimation Comments	[Not Specified]

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 7F- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-58.8
	Confidence Interval	(2-Sided) 95%; -76.7 to -40.9
	Estimation Comments	[Not Specified]

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 8- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-29.4
	Confidence Interval	(2-Sided) 95%; -46.1 to -12.7
	Estimation Comments	[Not Specified]

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 9N- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-35.3
	Confidence Interval	(2-Sided) 95%; -56.4 to -14.2
	Estimation Comments	[Not Specified]

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 9V- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-38.2
	Confidence Interval	(2-Sided) 95%; -58.2 to -18.2
	Estimation Comments	[Not Specified]

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 10A- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-61.8
	Confidence Interval	(2-Sided) 95%; -79.8 to -43.7
	Estimation Comments	[Not Specified]

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 11A- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-38.2
	Confidence Interval	(2-Sided) 95%; -59.3 to -17.2
	Estimation Comments	[Not Specified]

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 12F- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-58.8
	Confidence Interval	(2-Sided) 95%; -78.0 to -39.6
	Estimation Comments	[Not Specified]

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 14- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-17.6
	Confidence Interval	(2-Sided) 95%; -37.4 to 2.1
	Estimation Comments	[Not Specified]

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 15B- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-50.0
	Confidence Interval	(2-Sided) 95%; -69.6 to -30.4
	Estimation Comments	[Not Specified]

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 17F- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-44.1
	Confidence Interval	(2-Sided) 95%; -64.0 to -24.2
	Estimation Comments	[Not Specified]

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 18C- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-61.8
	Confidence Interval	(2-Sided) 95%; -79.4 to -44.2
	Estimation Comments	[Not Specified]

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 19A- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-52.9
	Confidence Interval	(2-Sided) 95%; -72.3 to -33.6
	Estimation Comments	[Not Specified]

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 19F- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-58.8
	Confidence Interval	(2-Sided) 95%; -77.6 to -40.1
	Estimation Comments	[Not Specified]

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 20- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-70.6
	Confidence Interval	(2-Sided) 95%; -87.4 to -53.8
	Estimation Comments	[Not Specified]

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 22F- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-67.6
	Confidence Interval	(2-Sided) 95%; -84.8 to -50.5
	Estimation Comments	[Not Specified]

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 23F- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-47.1
	Confidence Interval	(2-Sided) 95%; -68.0 to -26.1
	Estimation Comments	[Not Specified]

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Serotype 33F- Difference in positive response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-50.0
	Confidence Interval	(2-Sided) 95%; -68.5 to -31.5
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Mean Level of Anti-Pneumococcal Antibody
Description	Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).
Time Frame	Immediately prior to 23-PPV and 4 and 8 weeks after 23-PPV

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title		Group A1	Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV boosted with 13-PCV and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		33	35	34
Geometric Mean (95% Confidence Interval); Unit of Measure: mcg/mL
Immediately prior to 23-PPV: Serotype : 1	Number Analyzed	33 participants	34 participants	34 participants
		0.84; (0.58 to 1.23)	1.05; (0.68 to 1.62)	1.02; (0.71 to 1.46)
Immediately prior to 23-PPV: Serotype : 2	Number Analyzed	33 participants	34 participants	34 participants
		0.98; (0.63 to 1.52)	1.27; (0.90 to 1.78)	1.25; (0.93 to 1.69)
Immediately prior to 23-PPV: Serotype : 3	Number Analyzed	33 participants	34 participants	34 participants
		0.93; (0.70 to 1.23)	1.35; (0.75 to 2.42)	0.95; (0.66 to 1.36)
Immediately prior to 23-PPV: Serotype : 4	Number Analyzed	33 participants	34 participants	34 participants
		0.37; (0.29 to 0.47)	0.88; (0.46 to 1.66)	0.59; (0.40 to 0.88)
Immediately prior to 23-PPV: Serotype : 5	Number Analyzed	33 participants	34 participants	34 participants
		0.77; (0.57 to 1.05)	1.22; (0.76 to 1.97)	1.31; (0.91 to 1.89)
Immediately prior to 23-PPV: Serotype : 6B	Number Analyzed	33 participants	34 participants	34 participants
		0.64; (0.46 to 0.88)	1.08; (0.70 to 1.68)	0.92; (0.60 to 1.39)
Immediately prior to 23-PPV: Serotype : 7F	Number Analyzed	33 participants	34 participants	34 participants
		1.04; (0.77 to 1.40)	0.76; (0.57 to 1.00)	0.94; (0.70 to 1.27)
Immediately prior to 23-PPV: Serotype : 8	Number Analyzed	33 participants	34 participants	34 participants
		0.89; (0.62 to 1.27)	0.96; (0.58 to 1.57)	0.91; (0.59 to 1.38)
Immediately prior to 23-PPV: Serotype : 9N	Number Analyzed	33 participants	34 participants	34 participants
		0.59; (0.40 to 0.86)	0.98; (0.62 to 1.54)	1.06; (0.68 to 1.64)
Immediately prior to 23-PPV: Serotype : 9V	Number Analyzed	33 participants	34 participants	34 participants
		0.51; (0.40 to 0.65)	1.09; (0.63 to 1.90)	0.74; (0.50 to 1.11)
Immediately prior to 23-PPV: Serotype : 10A	Number Analyzed	33 participants	34 participants	34 participants
		0.73; (0.52 to 1.03)	1.01; (0.67 to 1.53)	0.96; (0.73 to 1.26)
Immediately prior to 23-PPV: Serotype : 11F	Number Analyzed	33 participants	34 participants	34 participants
		1.09; (0.75 to 1.58)	1.08; (0.69 to 1.71)	1.03; (0.69 to 1.52)
Immediately prior to 23-PPV: Serotype : 12F	Number Analyzed	33 participants	34 participants	34 participants
		0.67; (0.49 to 0.93)	0.89; (0.35 to 2.24)	0.54; (0.35 to 0.83)
Immediately prior to 23-PPV: Serotype : 14	Number Analyzed	33 participants	34 participants	34 participants
		0.98; (0.68 to 1.42)	1.67; (1.04 to 2.69)	1.09; (0.71 to 1.68)
Immediately prior to 23-PPV: Serotype : 15B	Number Analyzed	33 participants	34 participants	34 participants
		0.68; (0.50 to 0.91)	0.96; (0.76 to 1.23)	1.18; (0.73 to 1.92)
Immediately prior to 23-PPV: Serotype : 17F	Number Analyzed	33 participants	34 participants	34 participants
		0.84; (0.58 to 1.22)	0.94; (0.68 to 1.30)	1.05; (0.75 to 1.48)
Immediately prior to 23-PPV: Serotype : 18C	Number Analyzed	33 participants	34 participants	34 participants
		1.11; (0.73 to 1.70)	1.04; (0.75 to 1.46)	1.14; (0.79 to 1.64)
Immediately prior to 23-PPV: Serotype : 19A	Number Analyzed	33 participants	34 participants	34 participants
		1.24; (0.88 to 1.74)	1.99; (1.15 to 3.43)	2.09; (1.26 to 3.46)
Immediately prior to 23-PPV: Serotype : 19F	Number Analyzed	33 participants	34 participants	34 participants
		1.06; (0.80 to 1.41)	1.13; (0.83 to 1.53)	1.16; (0.80 to 1.67)
Immediately prior to 23-PPV: Serotype : 20	Number Analyzed	33 participants	34 participants	34 participants
		1.38; (0.93 to 2.06)	2.13; (1.39 to 3.25)	1.29; (0.89 to 1.87)
Immediately prior to 23-PPV: Serotype : 22F	Number Analyzed	33 participants	34 participants	34 participants
		0.58; (0.43 to 0.78)	0.98; (0.60 to 1.59)	0.82; (0.55 to 1.20)
Immediately prior to 23-PPV: Serotype : 23F	Number Analyzed	33 participants	34 participants	34 participants
		0.68; (0.51 to 0.91)	0.77; (0.50 to 1.20)	0.96; (0.66 to 1.41)
Immediately prior to 23-PPV: Serotype : 33F	Number Analyzed	33 participants	34 participants	34 participants
		0.87; (0.62 to 1.22)	1.05; (0.75 to 1.46)	0.67; (0.52 to 0.85)
4 weeks after 23-PPV: Serotype : 1	Number Analyzed	33 participants	35 participants	34 participants
		1.16; (0.83 to 1.62)	1.46; (1.04 to 2.06)	11.58; (7.72 to 17.38)
4 weeks after 23-PPV: Serotype : 2	Number Analyzed	33 participants	35 participants	34 participants
		1.78; (1.23 to 2.57)	1.79; (1.26 to 2.56)	9.41; (6.80 to 13.01)
4 weeks after 23-PPV: Serotype : 3	Number Analyzed	33 participants	35 participants	34 participants
		1.58; (1.12 to 2.23)	1.56; (1.03 to 2.38)	2.76; (1.72 to 4.42)
4 weeks after 23-PPV: Serotype : 4	Number Analyzed	33 participants	35 participants	34 participants
		1.15; (0.59 to 2.24)	1.90; (1.11 to 3.23)	2.02; (1.32 to 3.08)
4 weeks after 23-PPV: Serotype : 5	Number Analyzed	33 participants	35 participants	34 participants
		1.09; (0.78 to 1.51)	1.44; (0.97 to 2.13)	10.16; (5.69 to 18.15)
4 weeks after 23-PPV: Serotype : 6B	Number Analyzed	33 participants	35 participants	34 participants
		1.28; (0.78 to 2.10)	1.69; (1.02 to 2.81)	3.94; (2.12 to 7.33)
4 weeks after 23-PPV: Serotype : 7F	Number Analyzed	33 participants	35 participants	34 participants
		1.73; (1.17 to 2.56)	1.10; (0.82 to 1.47)	4.92; (2.99 to 8.09)
4 weeks after 23-PPV: Serotype : 8	Number Analyzed	33 participants	35 participants	34 participants
		1.59; (1.10 to 2.29)	1.97; (1.30 to 2.99)	9.04; (6.42 to 12.73)
4 weeks after 23-PPV: Serotype : 9N	Number Analyzed	33 participants	35 participants	34 participants
		1.08; (0.71 to 1.63)	1.35; (0.86 to 2.12)	3.26; (2.02 to 5.28)
4 weeks after 23-PPV: Serotype : 9V	Number Analyzed	33 participants	35 participants	34 participants
		0.68; (0.50 to 0.93)	1.21; (0.80 to 1.82)	3.84; (2.37 to 6.21)
4 weeks after 23-PPV: Serotype : 10A	Number Analyzed	33 participants	35 participants	34 participants
		0.84; (0.56 to 1.25)	1.49; (0.95 to 2.32)	5.20; (3.27 to 8.28)
4 weeks after 23-PPV: Serotype : 11F	Number Analyzed	33 participants	35 participants	34 participants
		1.43; (1.02 to 2.03)	1.27; (0.86 to 1.87)	4.74; (3.17 to 7.09)
4 weeks after 23-PPV: Serotype : 12F	Number Analyzed	33 participants	35 participants	34 participants
		0.71; (0.40 to 1.25)	1.66; (0.78 to 3.52)	1.82; (1.11 to 2.99)
4 weeks after 23-PPV: Serotype : 14	Number Analyzed	33 participants	35 participants	34 participants
		2.02; (1.32 to 3.09)	4.83; (2.97 to 7.86)	12.51; (7.50 to 20.86)
4 weeks after 23-PPV: Serotype : 15B	Number Analyzed	33 participants	35 participants	34 participants
		1.24; (0.81 to 1.92)	1.91; (1.43 to 2.55)	5.60; (3.20 to 9.80)
4 weeks after 23-PPV: Serotype : 17F	Number Analyzed	33 participants	35 participants	34 participants
		1.51; (0.98 to 2.32)	1.35; (0.97 to 1.89)	5.33; (3.63 to 7.82)
4 weeks after 23-PPV: Serotype : 18C	Number Analyzed	33 participants	35 participants	34 participants
		2.05; (1.37 to 3.08)	1.19; (0.84 to 1.67)	7.35; (4.39 to 12.31)
4 weeks after 23-PPV: Serotype : 19A	Number Analyzed	33 participants	35 participants	34 participants
		2.04; (1.35 to 3.07)	2.95; (1.64 to 5.33)	8.96; (5.43 to 14.80)
4 weeks after 23-PPV: Serotype : 19F	Number Analyzed	33 participants	35 participants	34 participants
		1.56; (1.20 to 2.03)	1.58; (1.11 to 2.25)	5.09; (3.25 to 7.97)
4 weeks after 23-PPV: Serotype : 20	Number Analyzed	33 participants	35 participants	34 participants
		1.63; (1.14 to 2.33)	2.50; (1.61 to 3.87)	3.74; (2.39 to 5.86)
4 weeks after 23-PPV: Serotype : 22F	Number Analyzed	33 participants	35 participants	34 participants
		1.06; (0.71 to 1.58)	1.14; (0.83 to 1.57)	4.51; (2.93 to 6.95)
4 weeks after 23-PPV: Serotype : 23F	Number Analyzed	33 participants	35 participants	34 participants
		1.11; (0.77 to 1.60)	1.18; (0.86 to 1.62)	2.90; (1.81 to 4.66)
4 weeks after 23-PPV: Serotype : 33F	Number Analyzed	33 participants	35 participants	34 participants
		1.14; (0.82 to 1.58)	1.82; (1.27 to 2.62)	5.11; (3.25 to 8.05)
8 weeks after 23-PPV: Serotype : 1	Number Analyzed	31 participants	35 participants	34 participants
		1.32; (0.92 to 1.91)	1.34; (0.96 to 1.86)	11.38; (7.66 to 16.92)
8 weeks after 23-PPV: Serotype : 2	Number Analyzed	31 participants	35 participants	34 participants
		1.86; (1.16 to 2.99)	1.67; (1.19 to 2.36)	10.07; (7.33 to 13.83)
8 weeks after 23-PPV: Serotype : 3	Number Analyzed	31 participants	35 participants	34 participants
		1.68; (1.13 to 2.51)	1.33; (0.89 to 2.00)	2.99; (1.89 to 4.73)
8 weeks after 23-PPV: Serotype : 4	Number Analyzed	31 participants	35 participants	34 participants
		1.36; (0.64 to 2.89)	1.84; (1.07 to 3.16)	1.96; (1.30 to 2.96)
8 weeks after 23-PPV: Serotype : 5	Number Analyzed	31 participants	35 participants	34 participants
		1.18; (0.85 to 1.64)	1.21; (0.83 to 1.74)	9.17; (5.06 to 16.60)
8 weeks after 23-PPV: Serotype : 6B	Number Analyzed	31 participants	35 participants	34 participants
		1.72; (0.98 to 3.01)	1.94; (1.18 to 3.19)	4.85; (2.58 to 9.10)
8 weeks after 23-PPV: Serotype : 7F	Number Analyzed	31 participants	35 participants	34 participants
		1.73; (1.23 to 2.43)	1.07; (0.78 to 1.46)	4.95; (3.02 to 8.10)
8 weeks after 23-PPV: Serotype : 8	Number Analyzed	31 participants	35 participants	34 participants
		1.83; (1.24 to 2.71)	1.80; (1.22 to 2.65)	8.57; (6.03 to 12.19)
8 weeks after 23-PPV: Serotype : 9N	Number Analyzed	31 participants	35 participants	34 participants
		1.09; (0.75 to 1.60)	1.10; (0.74 to 1.63)	3.37; (2.11 to 5.40)
8 weeks after 23-PPV: Serotype : 9V	Number Analyzed	31 participants	35 participants	34 participants
		0.88; (0.65 to 1.18)	1.08; (0.73 to 1.58)	4.44; (2.75 to 7.16)
8 weeks after 23-PPV: Serotype : 10A	Number Analyzed	31 participants	35 participants	34 participants
		1.05; (0.58 to 1.88)	1.38; (0.91 to 2.12)	5.75; (3.63 to 9.11)
8 weeks after 23-PPV: Serotype : 11F	Number Analyzed	31 participants	35 participants	34 participants
		1.29; (0.91 to 1.84)	1.08; (0.74 to 1.57)	4.42; (2.95 to 6.61)
8 weeks after 23-PPV: Serotype : 12F	Number Analyzed	31 participants	35 participants	34 participants
		0.91; (0.57 to 1.43)	2.33; (1.09 to 4.98)	2.13; (1.30 to 3.49)
8 weeks after 23-PPV: Serotype : 14	Number Analyzed	31 participants	35 participants	34 participants
		2.06; (1.38 to 3.08)	4.87; (3.05 to 7.79)	12.29; (7.38 to 20.47)
8 weeks after 23-PPV: Serotype : 15B	Number Analyzed	31 participants	35 participants	34 participants
		1.25; (0.80 to 1.94)	1.66; (1.24 to 2.22)	5.76; (3.34 to 9.92)
8 weeks after 23-PPV: Serotype : 17F	Number Analyzed	31 participants	35 participants	34 participants
		1.48; (0.88 to 2.46)	1.29; (0.98 to 1.71)	5.57; (3.76 to 8.25)
8 weeks after 23-PPV: Serotype : 18C	Number Analyzed	31 participants	35 participants	34 participants
		2.29; (1.54 to 3.40)	1.18; (0.85 to 1.62)	7.14; (4.37 to 11.65)
8 weeks after 23-PPV: Serotype : 19A	Number Analyzed	31 participants	35 participants	34 participants
		2.35; (1.53 to 3.59)	3.21; (1.76 to 5.84)	9.56; (5.87 to 15.56)
8 weeks after 23-PPV: Serotype : 19F	Number Analyzed	31 participants	35 participants	34 participants
		1.74; (1.30 to 2.33)	1.56; (1.09 to 2.24)	4.91; (3.12 to 7.73)
8 weeks after 23-PPV: Serotype : 20	Number Analyzed	31 participants	35 participants	34 participants
		1.73; (1.13 to 2.66)	2.59; (1.71 to 3.92)	3.56; (2.31 to 5.50)
8 weeks after 23-PPV: Serotype : 22F	Number Analyzed	31 participants	35 participants	34 participants
		1.22; (0.70 to 2.12)	1.09; (0.79 to 1.50)	4.69; (3.11 to 7.09)
8 weeks after 23-PPV: Serotype : 23F	Number Analyzed	31 participants	35 participants	34 participants
		1.21; (0.83 to 1.77)	1.07; (0.79 to 1.44)	2.44; (1.58 to 3.76)
8 weeks after 23-PPV: Serotype : 33F	Number Analyzed	31 participants	35 participants	34 participants
		1.36; (0.96 to 1.92)	1.68; (1.23 to 2.30)	5.01; (3.16 to 7.95)

13. Secondary Outcome

Title	Percentage of Participants With Seroprotection
Description	Seroprotection was defined as specific hemagglutination inhibition (HI) titers >40 at 4 weeks after vaccination.
Time Frame	4 weeks after seasonal influenza vaccine administration

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Analysis applies to participants who received influenza vaccine (Groups A2 and B).

Arm/Group Title		Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		35	34
Measure Type: Number; Unit of Measure: percentage of participants
Strain = H1N1CA09	Number Analyzed	35 participants	33 participants
		71.4	97.0
Strain = BPHU13	Number Analyzed	33 participants	31 participants
		66.7	80.6
Strain = H3N2SW13	Number Analyzed	30 participants	27 participants
		66.7	92.6
Strain = BBRIS08	Number Analyzed	18 participants	16 participants
		55.6	75.0
Strain = AHK4801	Number Analyzed	5 participants	6 participants
		80.0	83.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H1N1CA09 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-25.5
	Confidence Interval	(2-Sided) 95%; -41.6 to -9.5
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BPHU13 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-14.0
	Confidence Interval	(2-Sided) 95%; -35.2 to 7.3
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H3N2SW13 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-25.9
	Confidence Interval	(2-Sided) 95%; -45.5 to -6.4
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BBRIS08 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-19.4
	Confidence Interval	(2-Sided) 95%; -50.7 to 11.8
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = AHK4801 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-3.3
	Confidence Interval	(2-Sided) 95%; -49.4 to 42.7
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Percentage of Participants With 2-Fold Increase in Strain-Specific HI Titers
Description	2-fold increase from prevaccination HI titer.
Time Frame	4 weeks after seasonal influenza vaccine administration

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Analysis applies to participants who received influenza vaccine (Groups A2 and B).

Arm/Group Title		Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		35	34
Measure Type: Number; Unit of Measure: percentage of participants
Strain = H1N1CA09	Number Analyzed	35 participants	32 participants
		45.7	87.5
Strain = BPHU13	Number Analyzed	33 participants	30 participants
		42.4	80.0
Strain = H3N2SW13	Number Analyzed	30 participants	26 participants
		36.7	96.2
Strain = BBRIS08	Number Analyzed	18 participants	15 participants
		27.8	73.3
Strain = AHK4801	Number Analyzed	5 participants	6 participants
		80.0	83.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H1N1CA09 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-41.8
	Confidence Interval	(2-Sided) 95%; -61.9 to -21.7
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BPHU13 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-37.6
	Confidence Interval	(2-Sided) 95%; -59.7 to -15.5
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H3N2SW13 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-59.5
	Confidence Interval	(2-Sided) 95%; -78.2 to -40.7
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BBRIS08 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-45.6
	Confidence Interval	(2-Sided) 95%; -76.0 to -15.1
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = AHK4801 (Group A2 minus Group B)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-3.3
	Confidence Interval	(2-Sided) 95%; -49.4 to 42.7
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Percentage of Participants With 4-Fold Increase in Strain-Specific HI Titers
Description	4-fold increase from prevaccination HI titer.
Time Frame	4 weeks after seasonal influenza vaccine administration

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Analysis applies to participants who received influenza vaccine (Groups A2 and B).

Arm/Group Title		Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		35	34
Measure Type: Number; Unit of Measure: percentage of participants
Strain = H1N1CA09	Number Analyzed	35 participants	32 participants
		20.0	81.3
Strain = BPHU13	Number Analyzed	33 participants	30 participants
		15.2	70.0
Strain = H3N2SW13	Number Analyzed	30 participants	26 participants
		10.0	92.3
Strain = BBRIS08	Number Analyzed	18 participants	15 participants
		16.7	53.3
Strain = AHK4801	Number Analyzed	5 participants	6 participants
		60.0	66.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H1N1CA09 - Difference in at least 4-fold response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-61.3
	Confidence Interval	(2-Sided) 95%; -80.2 to -42.3
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BPHU13 - Difference in at least 4-fold response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-54.8
	Confidence Interval	(2-Sided) 95%; -75.3 to -34.4
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H3N2SW13 - Difference in at least 4-fold response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-82.3
	Confidence Interval	(2-Sided) 95%; -97.1 to -67.5
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BBRIS08 - Difference in at least 4-fold response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-36.7
	Confidence Interval	(2-Sided) 95%; -67.2 to -6.1
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = AHK4801 - Difference in at least 4-fold response, Group A2 minus Group B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) 95%; -63.8 to 50.5
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Percentage of Participants With Seroconversion
Description	Seroconversion at 4 weeks after vaccination defined, as per protocol, as a prevaccination HI titer <10 and an HI titer >40 at 4 weeks after vaccination. Seroconversion at 4 weeks after vaccination, defined per FDA guidance, as either a) a pre-vaccination HI titer <10 and HI titer >/= 40 at 4 weeks after vaccination, or b) a pre-vaccination HI titer >/= 10 and at least 4-fold increase in HI antibody titer at 4 weeks after vaccination.
Time Frame	4 weeks after influenza immunization

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Analysis applies to participants who received influenza vaccine (Groups A2 and B).

Arm/Group Title		Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		35	34
Measure Type: Number; Unit of Measure: percentage of participants
Strain = H1N1CA09 (as per FDA guidance)	Number Analyzed	35 participants	32 participants
		20.0	81.3
Strain = H1N1CA09 (as per protocol)	Number Analyzed	7 participants	9 participants
		42.9	88.9
Strain = BPHU13 (as per FDA guidance)	Number Analyzed	33 participants	30 participants
		12.1	70.0
Strain = BPHU13 (as per protocol)	Number Analyzed	4 participants	9 participants
		0	55.6
Strain = H3N2SW13 (as per FDA guidance)	Number Analyzed	30 participants	26 participants
		10.0	88.5
Strain = H3N2SW13 (as per protocol)	Number Analyzed	5 participants	9 participants
		20.0	77.8
Strain = BBRIS08 (as per FDA guidance)	Number Analyzed	18 participants	15 participants
		16.7	53.3
Strain = BBRIS08 (as per protocol)	Number Analyzed	3 participants	4 participants
		0	25
Strain = AHK4801 (as per FDA guidance)	Number Analyzed	5 participants	6 participants
		60.0	66.7
Strain = AHK4801 (as per protocol)	Number Analyzed	0 participants	2 participants
			100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H1N1CA09 (Group A2 minus Group B) [FDA]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-61.3
	Confidence Interval	(2-Sided) 95%; -80.2 to -42.3
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H1N1CA09 (Group A2 minus Group B) [Protocol]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-46.0
	Confidence Interval	(2-Sided) 95%; -88.0 to -4.0
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BPHU13 (Group A2 minus Group B) [FDA]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-57.9
	Confidence Interval	(2-Sided) 95%; -77.7 to -38.1
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BPHU13 (Group A2 minus Group B) [Protocol]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-55.6
	Confidence Interval	(2-Sided) 95%; -88.0 to -23.1
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H3N2SW13 (Group A2 minus Group B) [FDA]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-78.5
	Confidence Interval	(2-Sided) 95%; -94.8 to -62.2
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = H3N2SW13 (Group A2 minus Group B) [Protocol]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-57.8
	Confidence Interval	(2-Sided) 95%; -100.0 to -13.4
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BBRIS08 (Group A2 minus Group B) [FDA]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-36.7
	Confidence Interval	(2-Sided) 95%; -67.2 to -6.1
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = BBRIS08 (Group A2 minus Group B) [Protocol]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-25.0
	Confidence Interval	(2-Sided) 95%; -67.4 to 17.4
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Group A2, Group B
	Comments	Strain = AHK4801 (Group A2 minus Group B) [FDA]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Normal Distribution Approximation
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) 95%; -63.8 to 50.5
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Strain-Specific Geometric Mean Titer Levels
Description	Geometric mean titers (GMTs) in participants in Groups A2 and B were measured 4 weeks after vaccination.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Analysis applies to participants who received influenza vaccine (Groups A2 and B).

Arm/Group Title		Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		35	34
Geometric Mean (95% Confidence Interval); Unit of Measure: hemagglutination inhibition titers
Prior to influenza vaccine: Strain = H1N1CA09	Number Analyzed	28 participants	24 participants
		126.5; (78.2 to 204.4)	86.0; (55.4 to 133.6)
4 weeks after influenza vaccine: Strain = H1N1CA09	Number Analyzed	32 participants	33 participants
		154.8; (103.8 to 230.8)	390.8; (264.0 to 578.4)
Prior to influenza vaccine: Strain = BPHU13	Number Analyzed	29 participants	22 participants
		67.7; (49.5 to 92.4)	54.0; (34.6 to 84.3)
4 weeks after influenza vaccine: Strain = BPHU13	Number Analyzed	31 participants	29 participants
		84.6; (64.3 to 111.3)	243.1; (156.3 to 377.9)
Prior to influenza vaccine: Strain = H3N2SW13	Number Analyzed	25 participants	17 participants
		110.0; (72.9 to 166.0)	62.6; (41.2 to 95.2)
4 weeks after influenza vaccine: Strain = H3N2SW13	Number Analyzed	26 participants	25 participants
		134.5; (94.9 to 190.5)	342.8; (219.1 to 536.3)
Prior to influenza vaccine: Strain = BBRIS08	Number Analyzed	15 participants	12 participants
		49.3; (35.2 to 69.0)	71.3; (35.7 to 142.3)
4 weeks after influenza vaccine: Strain = BBRIS08	Number Analyzed	16 participants	13 participants
		65.8; (43.6 to 99.3)	311.7; (167.4 to 580.5)
Prior to influenza vaccine: Strain = AHK4801	Number Analyzed	5 participants	5 participants
		52.8; (21.0 to 132.6)	45.9; (32.4 to 65.2)
4 weeks after influenza vaccine: Strain = AHK4801	Number Analyzed	5 participants	6 participants
		121.3; (70.4 to 208.8)	127.0; (55.1 to 292.7)

18. Secondary Outcome

Title	Ratio of Strain-Specific Geometric Mean Titer Levels Postvaccination to Prevaccination
Description	Strain-specific GMT ratios were calculated as post-vaccination : pre-vaccination.
Time Frame	Immediately prior to and 4 weeks after influenza vaccine

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Analysis applies to participants who received influenza vaccine (Groups A2 and B).

Arm/Group Title		Group A2	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Day 1 and then on Day 15, and then participants further received immunization course: TT containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH at 12 weeks post-OCR treatment until Week 24.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		35	34
Geometric Mean (Standard Deviation); Unit of Measure: ratio
Strain = H1N1CA09	Number Analyzed	28 participants	23 participants
		1.31 (1.04)	5.74 (21.05)
Strain = BPHU13	Number Analyzed	29 participants	21 participants
		1.35 (1.62)	6.45 (28.31)
Strain = H3N2SW13	Number Analyzed	25 participants	16 participants
		1.25 (0.94)	8.18 (11.70)
Strain = BBRIS08	Number Analyzed	15 participants	11 participants
		1.38 (1.90)	4.68 (9.19)
Strain = AHK4801	Number Analyzed	5 participants	4 participants
		2.30 (1.60)	2.83 (3.34)

19. Secondary Outcome

Title	Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions
Description	MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Mean (Standard Deviation); Unit of Measure: cubic centimeters (cm^3)
	10.76 (13.31)	7.53 (8.20)

20. Secondary Outcome

Title	MRI Parameters: Number of T2 Lesions
Description	MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Mean (Standard Deviation); Unit of Measure: lesions
	57.94 (45.43)	45.53 (28.61)

21. Secondary Outcome

Title	MRI Parameters: Categorical Number of T2 Lesions
Description	MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Data are reported for evaluable participants.

Arm/Group Title		Group A (A1 + A2)	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		68	34
Measure Type: Number; Unit of Measure: participants
Baseline: 0-5 lesions	Number Analyzed	66 participants	34 participants
		1	0
Baseline: 6-9 lesions	Number Analyzed	66 participants	34 participants
		1	1
Baseline: >9 lesions	Number Analyzed	66 participants	34 participants
		64	33

22. Secondary Outcome

Title	MRI Parameters: Number of Gadolinium (Gd)-Enhancing T1 Lesions
Description	MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP.

Arm/Group Title	Group A (A1 + A2)	Group B
Arm/Group Description:	Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed	68	34
Mean (Standard Deviation); Unit of Measure: lesions
	2.85 (10.93)	0.62 (2.65)

23. Secondary Outcome

Title	MRI Parameters: Categorical Number of Gd-enhancing T1 Lesions
Description	MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

OC population included all randomized participants who completed the ISP. Data are reported for evaluable participants.

Arm/Group Title		Group A (A1 + A2)	Group B
Arm/Group Description:		Participants received dual infusion of OCR 300 mg on Days 1 and 15, and then further received the following immunization course during the period from Week 12 to Week 24: TT containing adsorbed vaccine, 23-PPV and repeated administration with KLH. In addition, only Group A1 received 13-valent pneumococcal conjugate vaccine (13-PCV, booster to 23-PPV) and only Group A2 received influenza vaccine.	Participants received immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization study period.
Overall Number of Participants Analyzed		68	34
Measure Type: Number; Unit of Measure: participants
Baseline: 0 lesions	Number Analyzed	65 participants	34 participants
		44	31
Baseline: 1 lesions	Number Analyzed	65 participants	34 participants
		8	0
Baseline: 2 lesions	Number Analyzed	65 participants	34 participants