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Clinical Trial Results:
A Phase 3, Open-label, Non-controlled, Multi-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Subjects with Primary Immunodeficiency Diseases (PID)

Summary
EudraCT number	2022-001873-29
Trial protocol	Outside EU/EEA
Global end of trial date	20 Dec 2021

Results information
Results version number	v2(current)
This version publication date	15 Dec 2022
First version publication date	06 Jul 2022
Other versions	v1
Version creation reason

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

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Trial information

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Sponsor protocol code

TAK-664-3001

ISRCTN number

US NCT number

NCT04346108

WHO universal trial number (UTN)

U1111-1189-8055

Sponsor organisation name

Shire

Sponsor organisation address

300 Shire Way, Lexington, United States, MA 02421

Public contact

Study Director, Shire, ClinicalTransparency@shire.com

Scientific contact

Study Director, Shire, ClinicalTransparency@shire.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

20 Dec 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Dec 2021

Was the trial ended prematurely?

Main objective of the trial

The main objective of this study is to assess serum trough Immunoglobulin globulin G (IgG) concentrations following weekly administration of IGSC, 20% (Epoch 2) and serum trough IgG concentration after biweekly administration of IGSC, 20% in Japanese participants with PID.

Protection of trial subjects

All the participants were required to read and sign the Informed Consent Form

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Aug 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 17

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants took part in the study at 8 investigative sites in Japan from 11 August 2020 to 22 December 2021.

Screening details

Participants diagnosed with primary immunodeficiency diseases (PID) received immunoglobulin administered intravenously (IGIV) in Epoch 1, followed by immunoglobulin administered subcutaneously (IGSC) 20% in Epoch 2 and then followed by Epoch 3 respectively for up to approximately 50 weeks.

Period 1 title

Epoch 1 (13 weeks)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Assessor, Subject

Epoch 1: IGIV 200-600 mg/kg

Arm description

Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 or 4 weeks for up to 13 weeks.

Arm type

Experimental

Investigational medicinal product name

Immune Globulin Intravenous (IGIV)

Investigational medicinal product code

Other name

Immune Globulin Infusion (Human)

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received IGIV infusion.

Number of subjects in period 1	Epoch 1: IGIV 200-600 mg/kg
Started	17
Completed	17

Period 2 title

Epoch 2 (24 weeks after Epoch 1)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Assessor

Epoch 2: IGSC (20%) 50-200 mg/kg

Arm description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Arm type

Experimental

Investigational medicinal product name

Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)

Investigational medicinal product code

Other name

Immune Globulin Infusion (Human)

Pharmaceutical forms

Infusion

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received IGSC, 20% SC infusion.

Number of subjects in period 2	Epoch 2: IGSC (20%) 50-200 mg/kg
Started	17
Completed	15
Not completed	2
Consent withdrawn by subject	1
Withdrawal by Parent/Guardian	1

Period 3 title

Epoch 3 (12 weeks after Epoch 2)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Assessor

Epoch 3: IGSC (20%) 100-400 mg/kg

Arm description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.

Arm type

Experimental

Investigational medicinal product name

Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)

Investigational medicinal product code

Other name

Immune Globulin Infusion (Human)

Pharmaceutical forms

Infusion

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received IGSC, 20% SC infusion.

Number of subjects in period 3 ^[1]	Epoch 3: IGSC (20%) 100-400 mg/kg
Started	7
Completed	7

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Epoch 3 included those participants who completed Epoch 2 and were eligible to enter Epoch 3.

Baseline characteristics

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Subject analysis set title

Epoch 1: Immune Globulin Intravenous (IGIV)

Subject analysis set type

Full analysis

Subject analysis set description

Participants received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for up to 13 weeks.

Subject analysis set title

Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Subject analysis set title

Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.

Subject analysis set title

Age 2-7 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged 2-7 years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Age 8-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged 8-13 years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Age 2-11years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants aged 2-11 years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Age ≥12 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants aged >=12 years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Age 2-12years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants aged 2-12 years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Age ≥13 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants aged >=13 years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Age 2-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants aged 2-13 years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Age ≥14 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants aged 14 and above years received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for a total of 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

IGSC: Epoch 2: 2-13 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged 2-13 years received approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch2.

Subject analysis set title

IGSC: Epoch 2: >=14 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=14 years received approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2.

Subject analysis set title

IGSC: Epoch 3: 2-13 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged 2-13 years received approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

IGSC: Epoch 3: >=14 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=14 years received approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

IGIV: Epoch 1: 3-week interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 200 to 600 mg/kg of IGIV infusion for every 3 for a total of 13 weeks.

Subject analysis set title

IGIV: Epoch 1: 4-week interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 200 to 600 mg/kg of IGIV infusion for every 4 for a total of 13 weeks.

Subject analysis set title

IGSC: Epoch 3: Biweekly

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 1.

Subject analysis set title

IGSC: Epoch 2

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 50 to 200 mg/kg of IGSC infusion, 20% once a week for a total of 24 weeks after Epoch 1.

Subject analysis set title

IGIV 200 to 600 mg/kg + IGSC [50 to 200 and 100 to 400] mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks up to 13 weeks in Epoch 1; followed by approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2; followed by approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

Epoch 2: IGSC (20%) 50-200 mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Subject analysis set title

Epoch 3: IGSC (20%) 100-400 mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.

Subject analysis set title

Epoch 1: IGIV 3-week Interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 weeks for up to 13 weeks.

Subject analysis set title

Epoch 1: IGIV 4-week Interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 4 weeks for up to 13 weeks.

Subject analysis set title

Epoch 2: IGSC, 20% Weekly

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Subject analysis set title

Epoch 2: IGSC, 20% Weekly (EOS [Week 25]/ ET)

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to end of study (EOS) (24 weeks) or early termination (ET) after Epoch 1.

Subject analysis set title

Epoch 3: IGSC, 20% Biweekly

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to EOS (13 weeks) after Epoch 2.

Subject analysis set title

Epoch 3: IGSC, 20% Biweekly (Week 13)

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to EOS (13 weeks) after Epoch 2.

Subject analysis sets values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)	Age 2-7 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age 8-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age 2-11years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age ≥12 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age 2-12years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age ≥13 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age 2-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age ≥14 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	IGSC: Epoch 2: 2-13 years	IGSC: Epoch 2: >=14 years	IGSC: Epoch 3: 2-13 years	IGSC: Epoch 3: >=14 years	IGIV: Epoch 1: 3-week interval	IGIV: Epoch 1: 4-week interval	IGSC: Epoch 3: Biweekly	IGSC: Epoch 2	IGIV 200 to 600 mg/kg + IGSC [50 to 200 and 100 to 400] mg/kg	Epoch 2: IGSC (20%) 50-200 mg/kg	Epoch 3: IGSC (20%) 100-400 mg/kg	Epoch 1: IGIV 3-week Interval	Epoch 1: IGIV 4-week Interval	Epoch 2: IGSC, 20% Weekly	Epoch 2: IGSC, 20% Weekly (EOS [Week 25]/ ET)	Epoch 3: IGSC, 20% Biweekly	Epoch 3: IGSC, 20% Biweekly (Week 13)
Number of subjects	17	17	7	2	4	4	13	6	11	6	11	4	6	2	7	17	17	7	17	17	17	7	5	12	17	10	7	7
Age Categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	31.0 ( 21.13 )	( )	( )	( )	( )	( )	( )	( )	( )
Gender categorical
Units: Subjects
Female																				7	0	0	0	0	0	0	0	0
Male																				10	0	0	0	0	0	0	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino																				0	0	0	0	0	0	0	0	0
Not Hispanic or Latino																				17	0	0	0	0	0	0	0	0
Unknown or Not Reported																				0	0	0	0	0	0	0	0	0
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native																				0	0	0	0	0	0	0	0	0
Asian																				17	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander																				0	0	0	0	0	0	0	0	0
Black or African American																				0	0	0	0	0	0	0	0	0
White																				0	0	0	0	0	0	0	0	0
More than one race																				0	0	0	0	0	0	0	0	0
Unknown or Not Reported																				0	0	0	0	0	0	0	0	0
Weight
Units: kilogram (kg)
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	48.16 ( 18.120 )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )
Height
Units: centimeter (cm)
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	152.15 ( 20.076 )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )
Body Mass Index (BMI)
BMI is calculated as [weight (kg) / height(m)^2]
Units: kg/m^2
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	19.88 ( 3.242 )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )

End points

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Reporting group title

Epoch 1: IGIV 200-600 mg/kg

Reporting group description

Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 or 4 weeks for up to 13 weeks.

Reporting group title

Epoch 2: IGSC (20%) 50-200 mg/kg

Reporting group description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Reporting group title

Epoch 3: IGSC (20%) 100-400 mg/kg

Reporting group description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.

Subject analysis set title

Epoch 1: Immune Globulin Intravenous (IGIV)

Subject analysis set type

Full analysis

Subject analysis set description

Participants received 200 to 600 mg/kg of IGIV infusion for every 3 or 4 weeks for up to 13 weeks.

Subject analysis set title

Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Subject analysis set title

Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.

Subject analysis set title

Age 2-7 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Age 8-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Age 2-11years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Age ≥12 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Age 2-12years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Age ≥13 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Age 2-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Age ≥14 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

IGSC: Epoch 2: 2-13 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged 2-13 years received approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch2.

Subject analysis set title

IGSC: Epoch 2: >=14 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=14 years received approximately 50 to 200 mg/kg of IGSC infusion,20% once a week for a total of 24 weeks after Epoch 1 in Epoch 2.

Subject analysis set title

IGSC: Epoch 3: 2-13 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged 2-13 years received approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

IGSC: Epoch 3: >=14 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=14 years received approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 2 in Epoch 3.

Subject analysis set title

IGIV: Epoch 1: 3-week interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 200 to 600 mg/kg of IGIV infusion for every 3 for a total of 13 weeks.

Subject analysis set title

IGIV: Epoch 1: 4-week interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 200 to 600 mg/kg of IGIV infusion for every 4 for a total of 13 weeks.

Subject analysis set title

IGSC: Epoch 3: Biweekly

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks for a total of 12 weeks after Epoch 1.

Subject analysis set title

IGSC: Epoch 2

Subject analysis set type

Full analysis

Subject analysis set description

Participants received approximately 50 to 200 mg/kg of IGSC infusion, 20% once a week for a total of 24 weeks after Epoch 1.

Subject analysis set title

IGIV 200 to 600 mg/kg + IGSC [50 to 200 and 100 to 400] mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Epoch 2: IGSC (20%) 50-200 mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Subject analysis set title

Epoch 3: IGSC (20%) 100-400 mg/kg

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.

Subject analysis set title

Epoch 1: IGIV 3-week Interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 weeks for up to 13 weeks.

Subject analysis set title

Epoch 1: IGIV 4-week Interval

Subject analysis set type

Full analysis

Subject analysis set description

Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 4 weeks for up to 13 weeks.

Subject analysis set title

Epoch 2: IGSC, 20% Weekly

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Subject analysis set title

Epoch 2: IGSC, 20% Weekly (EOS [Week 25]/ ET)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Epoch 3: IGSC, 20% Biweekly

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to EOS (13 weeks) after Epoch 2.

Subject analysis set title

Epoch 3: IGSC, 20% Biweekly (Week 13)

Subject analysis set type

Full analysis

Subject analysis set description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to EOS (13 weeks) after Epoch 2.

Primary: Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2

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End point title

Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2 ^[1]

End point description

Total serum trough levels of IgG antibodies measured during period 2 of Epoch 2 were assessed. Pharmacokinetic Analysis Set (PKAS) 1 included all participants in the all-treated set who have had at least 1 evaluable serum IgG concentration value and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Only PKAS 1 participants in Epoch 2 were analyzed for this outcome measure.Total serum trough levels of IgG antibodies measured during period 2 of Epoch 2 were assessed.

End point type

Primary

End point timeframe

Epoch 2 (period 2): Up to 24 weeks

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this primary end point.

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	17
Units: grams per liter (g/L)
geometric mean (confidence interval 95%)	8.56 (8.03 to 9.12)

No statistical analyses for this end point

Primary: Epoch 3: Total Serum Trough Levels of IgG Antibodies

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End point title

Epoch 3: Total Serum Trough Levels of IgG Antibodies ^[2]

End point description

Total serum trough levels of IgG antibodies measured during Epoch 3 were assessed. PKAS 1 included all participants in the all-treated set who have had at least 1 evaluable serum IgG concentration value and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Only PKAS 1 participants in Epoch 3 were analyzed for this outcome measure.

End point type

Primary

End point timeframe

Epoch 3: Up to Week 12

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this primary end point.

End point values	Epoch 3: IGSC (20%) 100-400 mg/kg
Number of subjects analysed	7
Units: g/L
geometric mean (confidence interval 95%)	8.39 (7.89 to 8.91)

No statistical analyses for this end point

Secondary: Epoch 1: Total Serum Trough Levels of IgG Antibodies

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End point title

Epoch 1: Total Serum Trough Levels of IgG Antibodies

End point description

Total serum trough levels of IgG antibodies measured during Epoch 1 were assessed. PKAS 1 included all participants in the all-treated set who have had at least 1 evaluable serum IgG concentration value and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Only PKAS 1 participants in Epoch 1 were analyzed for this outcome measure.

End point type

Secondary

End point timeframe

Epoch 1: Up to Week 13

End point values	Epoch 1: IGIV 200-600 mg/kg
Number of subjects analysed	17
Units: g/L
geometric mean (confidence interval 95%)	8.18 (7.71 to 8.68)

No statistical analyses for this end point

Secondary: Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG

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End point title

Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG

End point description

PKAS 2 included all participants >=12 years of age in the all-treated set who have had at least 1 evaluable serum IgG concentration value during Epoch 2 and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Overall number analyzed are the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: g*day/L
geometric mean (confidence interval 95%)	58.9 (48.7 to 71.3)

No statistical analyses for this end point

Secondary: Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses

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End point title

Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses

End point description

Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined. PKAS 2 included all participants >=12 years of age in the all-treated set who have had at least 1 evaluable serum IgG concentration value during Epoch 2 and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Overall number analyzed are the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: g*day/L
geometric mean (confidence interval 95%)
IgG 1	35.8 (32.4 to 39.5)
IgG 2	23.4 (20.4 to 26.9)
IgG 3	1.32 (0.624 to 2.80)
IgG 4	1.67 (1.10 to 2.53)

No statistical analyses for this end point

Secondary: Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG

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End point title

Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: mL/kg/day
geometric mean (confidence interval 95%)	1.93 (1.71 to 2.19)

No statistical analyses for this end point

Secondary: Epoch 2: CL/F for Total Serum Levels of IgG Subclasses

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End point title

Epoch 2: CL/F for Total Serum Levels of IgG Subclasses

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: mL/kg/day
geometric mean (confidence interval 95%)
IgG 1	3.18 (2.88 to 3.51)
IgG 2	4.86 (4.18 to 5.66)
IgG 3	99.5 (37.1 to 266)
IgG 4	68.3 (48.3 to 96.6)

No statistical analyses for this end point

Secondary: Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG

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End point title

Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: g/L
geometric mean (confidence interval 95%)	9.08 (7.46 to 11.1)

No statistical analyses for this end point

Secondary: Epoch 2: Cmax for Total Serum Levels of IgG Subclasses

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End point title

Epoch 2: Cmax for Total Serum Levels of IgG Subclasses

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: g/L
geometric mean (confidence interval 95%)
IgG 1	5.40 (4.95 to 5.89)
IgG 2	3.51 (3.06 to 4.03)
IgG 3	0.202 (0.0960 to 0.425)
IgG 4	0.256 (0.169 to 0.387)

No statistical analyses for this end point

Secondary: Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG

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End point title

Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: g/L
geometric mean (confidence interval 95%)	7.45 (6.17 to 8.99)

No statistical analyses for this end point

Secondary: Epoch 2: Cmin for Total Serum Levels of IgG Subclasses

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End point title

Epoch 2: Cmin for Total Serum Levels of IgG Subclasses

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: g/L
geometric mean (confidence interval 95%)
IgG 1	4.89 (4.34 to 5.51)
IgG 2	3.15 (2.70 to 3.68)
IgG 3	0.181 (0.0861 to 0.381)
IgG 4	0.218 (0.153 to 0.311)

No statistical analyses for this end point

Secondary: Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG

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End point title

Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: hours
median (full range (min-max))	71.08 (22.82 to 168.23)

No statistical analyses for this end point

Secondary: Epoch 2: Tmax for Total Serum Levels of IgG Subclasses

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End point title

Epoch 2: Tmax for Total Serum Levels of IgG Subclasses

End point description

End point type

Secondary

End point timeframe

Epoch 2: Week 21

End point values	Epoch 2: IGSC (20%) 50-200 mg/kg
Number of subjects analysed	7
Units: hours
median (full range (min-max))
IgG 1	71.08 (22.82 to 118.80)
IgG 2	71.08 (0.00 to 164.32)
IgG 3	72.92 (71.08 to 118.80)
IgG 4	71.17 (70.13 to 118.80)

No statistical analyses for this end point

Secondary: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)

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End point title

Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)

End point description

Trough levels of specific antibodies to clinically relevant pathogen (Clostridium tetani toxoid and HBV) were assessed in Epoch 1, Epoch 2 and Epoch 3. Data was analyzed per interval in each Epoch for this outcome measure. PKAS 1 included all participants in the all-treated set who have had at least 1 evaluable serum IgG concentration value and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Overall number analyzed are the number of participants available for analyses. Data is represented as per doses received for specific interval in each Epoch for this outcome measure.

End point type

Secondary

End point timeframe

Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)

End point values	Epoch 1: IGIV 3-week Interval	Epoch 1: IGIV 4-week Interval	Epoch 2: IGSC, 20% Weekly	Epoch 2: IGSC, 20% Weekly (EOS [Week 25]/ ET)	Epoch 3: IGSC, 20% Biweekly	Epoch 3: IGSC, 20% Biweekly (Week 13)
Number of subjects analysed	5	12	17	10	7	7
Units: International units (IU)/mL
geometric mean (confidence interval 95%)
Clostridium Tetani Toxoid	0.524 (0.290 to 0.949)	0.602 (0.364 to 0.997)	0.674 (0.468 to 0.970)	1.52 (1.11 to 2.08)	1.97 (1.65 to 2.35)	1.80 (1.35 to 2.39)
Hepatitis B virus	22.7 (17.8 to 43.0)	35.2 (17.5 to 70.9)	54.1 (33.7 to 87.0)	486 (335 to 706)	645 (452 to 920)	923 (832 to 1020)

No statistical analyses for this end point

Secondary: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)

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End point title

Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)

End point description

Trough levels of specific antibodies to clinically relevant pathogens (HIB) were assessed in Epoch 1, Epoch 2 and Epoch 3. Data was analyzed per interval in each Epoch for this outcome measure. PKAS 1 included all participants in the all-treated set who have had at least 1 evaluable serum IgG concentration value and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Overall number analyzed are the number of participants available for analyses. Data is represented as per doses received for specific intervals in each Epoch for this outcome measure.

End point type

Secondary

End point timeframe

Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)

End point values	Epoch 1: IGIV 3-week Interval	Epoch 1: IGIV 4-week Interval	Epoch 2: IGSC, 20% Weekly	Epoch 2: IGSC, 20% Weekly (EOS [Week 25]/ ET)	Epoch 3: IGSC, 20% Biweekly	Epoch 3: IGSC, 20% Biweekly (Week 13)
Number of subjects analysed	5	12	17	10	7	7
Units: mg/L
geometric mean (confidence interval 95%)	1.58 (0.568 to 4.38)	1.55 (1.11 to 2.18)	2.50 (1.95 to 3.20)	1.77 (1.07 to 2.91)	2.04 (1.74 to 2.39)	1.73 (1.46 to 2.04)

No statistical analyses for this end point

Secondary: Health Related Quality of Life: Treatment Preference

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End point title

Health Related Quality of Life: Treatment Preference

End point description

Treatment preference questionnaire is self-administered questionnaire developed to assess participants' preference towards administration of new IGSC therapy. There are 4-items on questionnaire, which investigate participant's preference on clinic/hospital/home setting of receiving the immunoglobulin (Ig) therapy, the participant's rating on the frequency and method of administration, and the participant's preference to continue receiving the IGSC treatment. The questionnaire included following categories: Q1=Where do you prefer to receive your immunoglobulin therapy, Q2=The Frequency of Administration: Liked Very Much, Q3=The Frequency of Administration: Liked. As pre-specified in protocol, data is reported per age (2-13 and >=14 years). All-Treated Set=all enrolled participants of age ‘2-13 years’ and ‘>=14 years’ who received at least 1 dose of study drug (IGIV or IGSC). 'n' = Number analyzed is the number of participants with data available for analyses at specific timepoints.

End point type

Secondary

End point timeframe

Up to approximately 1.5 years

End point values	IGSC: Epoch 2: 2-13 years	IGSC: Epoch 2: >=14 years	IGSC: Epoch 3: 2-13 years	IGSC: Epoch 3: >=14 years
Number of subjects analysed	4	6	2	5
Units: participants
Where do you Prefer to Receive Ig Therapy-At Home	3	1	1	4
The Frequency of Administration: Liked Very Much	2	1	1	4
The Frequency of Administration: Liked	1	3	1	1

No statistical analyses for this end point

Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs)

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End point title

Number of Participants with Treatment Emergent Adverse Events (TEAEs)

End point description

TEAEs was defined as adverse events (AEs) with onset after date-time of first dose of study drug, or medical conditions present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Any TEAE that is recorded by the investigator as "possibly related" or "probably related" to IP was considered as IGSC, 20%-related AE, and any AE recorded as "unlikely related" or "not related" was considered as unrelated AE. AEs included vital signs, clinical laboratory measurements. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: participants	11	16	3

No statistical analyses for this end point

Secondary: Number of Participants with Tolerability Events Related to the Infusion of Study Drug

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End point title

Number of Participants with Tolerability Events Related to the Infusion of Study Drug

End point description

An infusion is considered tolerable if the infusion rate was not reduced, or the infusion was not interrupted or stopped, due to TEAE related to study drug (IGIV or IGSC) infusion. A tolerability event is considered to have occurred if an infusion was not tolerable in Epoch 1, Epoch 2 and Epoch 3. Number of participants with tolerability events related to infusion of IP were assessed. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: participants
Infusions With Infusion Rate Reduced	0	0	0
Infusions That Were Interrupted	0	1	0
Infusions That Were Stopped	0	0	0
Infusion Rate Reduced/Interrupted/Stopped	0	1	0

No statistical analyses for this end point

Secondary: Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)

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End point title

Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)

End point description

The ASBI rate was calculated as the mean number of acute serious bacterial infections per participants per year. Annual rate of validated acute serious bacterial infections per participant was assessed. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: number of infections per year
arithmetic mean (standard deviation)	0.0 ( 0.00 )	0.25 ( 1.042 )	0.0 ( 0.00 )

No statistical analyses for this end point

Secondary: Annual Rate of All Infections Per Year

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End point title

Annual Rate of All Infections Per Year

End point description

Annual rate is the number of participants reporting any infection per year. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: number of infections per year
arithmetic mean (standard deviation)	1.65 ( 2.479 )	2.78 ( 3.074 )	0.00 ( 0.000 )

Epoch 1: IGIV

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

3.15

Epoch 3: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Epoch 2: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

2.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

4.13

Secondary: Number of Days Participants not Able to Attend School or Work to Perform Normal Daily Activities due to Illness/Infection

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End point title

Number of Days Participants not Able to Attend School or Work to Perform Normal Daily Activities due to Illness/Infection

End point description

Number of days not able to attend school or work to perform normal daily activities due to illness/infection are standardized per year (365.25 days). The number of days not able to attend school or work to perform normal daily activities due to illness/infection were assessed. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: days
median (full range (min-max))	0.00 (0.0 to 16.1)	0.00 (0.0 to 17.2)	4.30 (0.0 to 38.7)

Epoch 1: IGIV

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

5.3

Epoch 2: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

2.87

Confidence interval

level

95%

sides

2-sided

lower limit

1.37

upper limit

5.18

Epoch 3: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

9.82

Confidence interval

level

95%

sides

2-sided

lower limit

2.82

upper limit

23.82

Secondary: Number of Days Participants Were on Antibiotics

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End point title

Number of Days Participants Were on Antibiotics

End point description

Number of days on antibiotics is defined as the number of days those antibiotics were taken as concomitant medications and is standardized to per year (365.25 days). Antibiotics are defined as any medication under anatomical therapeutic chemical Level 2 therapeutic class “ANTIBACTERIALS FOR SYSTEMIC USE”. If a participant took multiple antibiotics on a single day, that day is counted for only once. Protocol defined prophylactic antibiotics for viral, fungal or protozoal infections (e.g. trimethoprim/sulfamethoxazole twice a week for pneumocystis) which are not treated by immunoglobulin, were excluded from this analysis. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: days
median (full range (min-max))	0.00 (0.0 to 31.8)	0.00 (0.0 to 34.5)	0.00 (0.0 to 21.5)

Epoch 1: IGIV

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

4.01

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

8.54

Epoch 2: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

5.87

Confidence interval

level

95%

sides

2-sided

lower limit

2.32

upper limit

11.93

Epoch 3: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

3.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

10.74

Secondary: Number of Participants Hospitalized due to Illness or Infection

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End point title

Number of Participants Hospitalized due to Illness or Infection

End point description

Number of participants with hospitalization are standardized to per year (365.25 days). A hospitalization is counted for a specific epoch only if that hospitalization started during that epoch. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: participants	0	1	0

Epoch 1: IGIV

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Epoch 3: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Epoch 2: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.35

Secondary: Length of Hospital Stay

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End point title

Length of Hospital Stay

End point description

Length of hospital stay per stay is standardized to per year (365.25 days). A hospitalization is counted for a specific epoch only if that hospitalization started during that epoch. All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: days
median (full range (min-max))	0.00 (0.0 to 0.0)	0.00 (0.0 to 17.4)	0.00 (0.0 to 0.0)

Epoch 1: IGIV

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Epoch 3: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Epoch 2: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

2.76

Secondary: Number of Acute Physician Visits due to Illness/Infection

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End point title

Number of Acute Physician Visits due to Illness/Infection

End point description

Number of acute physician visits is standardized to per year (365.25 days). All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

End point type

Secondary

End point timeframe

From first dose of study drug up to end of study (up to approximately 1.5 years)

End point values	Epoch 1: Immune Globulin Intravenous (IGIV)	Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)	Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Number of subjects analysed	17	17	7
Units: number of visits per year
arithmetic mean (standard deviation)	1.18 ( 3.098 )	3.30 ( 6.807 )	0.61 ( 1.624 )

Epoch 1: IGIV

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

2.68

Epoch 3: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

2.15

Epoch 2: IGSC

Comparison groups

Epoch 1: Immune Globulin Intravenous (IGIV) v Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC) v Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Poisson Estimate

Point estimate

2.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

4.82

Secondary: Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score

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End point title

Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score

End point description

Peds-QL=generic HR QoL instrument designed specifically for pediatrics has domains as:general health/activities,feelings/emotional,social functioning,school functioning.In this study,2-7 years (parent as observer),8-13 years (participant as observer) for Peds-QL health questionnaire was analyzed.Higher scores=better QOL for all domains.This modular instrument used 5-point scale:0(never) to 4(almost always).Items are reversed scored;linearly transformed to 0-100 scale as follows:0=100,1=75,2=50,3=25,4=0.4 dimensions(physical, emotional, social, & school functioning) are scored.PEDS-QL Total Scale Score has 0-100 scale,higher scores=better HRQoL. All-Treated Set included all enrolled participants of age group ‘2-7 years’ and ‘8-13 years’ who received at least 1 dose of study drug (IGIV or IGSC). 'n' indicates = Number analyzed are the number of participants with data available for analysis at the given timepoint.

End point type

Secondary

End point timeframe

Baseline up to end of study (approximately 1.5 years)

End point values	Age 2-7 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age 8-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg
Number of subjects analysed	2	4
Units: score on a scale
arithmetic mean (standard deviation)
IGIV: Epoch 1: Baseline (Week 1)(n=2,4)	88.04 ( 13.835 )	87.23 ( 11.820 )
IGSC: Epoch 2: CFB (Week 1)(n=2,4)	9.78 ( 15.372 )	-6.79 ( 9.977 )
IGSC: Epoch 3: CFB (Week 1)[n=1,1]	14.13 ( 999 )	20.65 ( 999 )
IGSC: Epoch 3: CFB (EOS/ET)(n=2,4)	3.26 ( 7.686 )	4.08 ( 16.374 )

No statistical analyses for this end point

Secondary: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score

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End point title

EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score

End point description

EQ-5D-3L health questionnaire=participant answered questionnaire scoring 5 dimensions -mobility,self-care,usual activities, pain/discomfort and anxiety/depression. n this study, 2-11 years (parent as observer),12 years and older (participant as observer) for EQ-5D-3L health questionnaire was analyzed.Health state index score range from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.EQ visual analogue scale range from 0 to 100, where higher scores indicate better health status.Data is reported as per age groups (2-11 years and >=12 years). All-Treated Set included all enrolled participants of age group ‘2-11 years’ and ‘>=12 years’ who received at least 1 dose of study drug (IGIV or IGSC). Number analyzed is the number of participants with data available for analyses at specific timepoints.

End point type

Secondary

End point timeframe

Baseline up to end of the study (approximately 1.5 years)

End point values	Age 2-11years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age ≥12 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg
Number of subjects analysed	4	13
Units: score on a scale
arithmetic mean (standard deviation)
IGIV: Epoch 1: Baseline (Week 1): HSIS(n=4,13)	0.8080 ( 0.04619 )	0.8217 ( 0.04544 )
IGIV: Epoch 1: Baseline (Week 1): EQVAS(n=4,13)	87.5 ( 15.55 )	77.1 ( 22.16 )
IGSC: Epoch 2: CFB (Week 1): HSIS (n=3,13)	-0.0270 ( 0.12275 )	0.0016 ( 0.03318 )
IGSC: Epoch 2: CFB (Week 1): EQVAS (n=3,13)	-5.0 ( 5.00 )	4.2 ( 17.15 )
IGSC: Epoch 3:CFB (Week 1): HSIS (n=1,6)	0.0000 ( 999 )	0.0133 ( 0.03266 )
IGSC: Epoch 3:CFB (Week 1): EQVAS (n=1,6)	0.0 ( 999 )	-1.3 ( 12.39 )
IGSC: Epoch 3:CFB (EOS/ET):HSIS(n=4,13)	0.0400 ( 0.04619 )	0.0229 ( 0.04566 )
IGSC: Epoch 3:CFB (EOS/ET): EQVAS(n=4,13)	1.3 ( 6.29 )	6.9 ( 13.21 )

No statistical analyses for this end point

Secondary: Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score

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End point title

Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score

End point description

SF-36=generic quality-of-life instrument that has been widely used to assess HRQL of participants.In this study, 14 years and older (participant as observer) for SF-36 health questionnaire was analyzed. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases.SF-36=36 items aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100.Higher scores=better HRQL. As pre-specified in protocol data is reported for participants with age group of 14 years or older.All-Treated Set included all enrolled participants of age ’14 years and above’ who received at least 1 dose of study drug (IGIV or IGSC).‘n’=Number analysed are participants with data available for analysis.Physical Component Summary Score (PCSS), Mental Component Summary Score (MCSS).

End point type

Secondary

End point timeframe

Baseline up to end of the study (approximately 1.5 years)

End point values	Age ≥14 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg
Number of subjects analysed	11
Units: score on a scale
arithmetic mean (standard deviation)
IGIV: Epoch 1: Baseline (Week 1): PCSS(n=11)	50.21 ( 7.282 )
IGIV: Epoch 1: Baseline (Week 1): MCSS(n=11)	50.59 ( 8.114 )
IGSC: Epoch 2: CFB (Week 1): PCSS(n=11)	0.10 ( 7.142 )
IGSC: Epoch 2: CFB (Week 1): MCSS(n=11)	-0.30 ( 2.294 )
IGSC: Epoch 3: CFB (Week 1): PCSS(n=5)	1.81 ( 8.189 )
IGSC: Epoch 3: CFB (Week 1): MCSS (n=5)	3.60 ( 5.352 )
IGSC: Epoch 3:CFB (EOS/ET):PCSS(n=10)	0.23 ( 4.649 )
IGSC: Epoch 3:CFB (EOS/ET):MCSS(n=10)	4.32 ( 8.185 )

No statistical analyses for this end point

Secondary: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score

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End point title

Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score

End point description

TSQM=is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. In this study, 2-12 years (parent as observer), 13 years and older (participant as observer) for TSQM health questionnaire will be analyzed. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain. As pre-specified in protocol, data is reported as per age group (2-12 years and >=13 years). All-Treated Set included all enrolled participants of age group ‘ 2-12 years’ and ‘>=3 years’ who received at least 1 dose of study drug (IGIV or IGSC). 'n' indicates number analyzed is the number of participants with data available for analyses at specific timepoints.

End point type

Secondary

End point timeframe

Baseline up to end of the study (approximately 1.5 years)

End point values	Age 2-12years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age ≥13 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg
Number of subjects analysed	6	11
Units: score on a scale
arithmetic mean (standard deviation)
IGIV:Epoch1:Baseline(Week1):Effectiveness(n=6,11)	69.44 ( 14.380 )	75.25 ( 18.817 )
IGIV:Epoch 1:Baseline(Week 1):Convenience(n=6,11)	62.96 ( 13.907 )	65.66 ( 23.016 )
IGIV: Epoch 1: Baseline (Week 1): GS(n=6,11)	75.00 ( 17.928 )	74.68 ( 18.173 )
IGSC: Epoch 2: CFB (Week 1): Effectiveness(n=5,11)	2.22 ( 9.296 )	-1.52 ( 10.568 )
IGSC: Epoch 2: CFB (Week 1): Convenience (n=5,11)	3.33 ( 16.942 )	5.05 ( 13.484 )
IGSC: Epoch 2: CFB (Week 1): GS (n=5,11)	-2.86 ( 10.833 )	1.30 ( 10.507 )
IGSC: Epoch 3: CFB (Week 1): Effectiveness (n=2,5)	2.78 ( 3.928 )	-10.00 ( 52.673 )
IGSC: Epoch 3: CFB (Week 1): Convenience (n=2,5)	13.89 ( 19.642 )	15.56 ( 12.669 )
IGSC: Epoch 3: CFB (Week 1): GS (n=2,5)	-7.14 ( 10.02 )	4.29 ( 29.709 )
IGSC:Epoch 3:CFB (EOS/ET):Effectiveness(n=6,11)	9.26 ( 10.924 )	6.57 ( 18.892 )
IGSC: Epoch 3:CFB (EOS/ET): Convenience (n=6,11)	5.56 ( 22.222 )	9.09 ( 23.210 )
IGSC: Epoch 3: CFB (EOS/ET): GS(n=6,11)	7.14 ( 23.905 )	3.90 ( 23.768 )

No statistical analyses for this end point

Secondary: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score

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End point title

Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score

End point description

LQI=self-administered questionnaire developed specifically for participants/legal guardians involved in IGIV treatments.2-13 years (parent as observer),14 years and older (participant as observer) for LQI health questionnaire was analyzed.LQI=15-items, divided into 4 domains: treatment interferences(TI)[6 items],therapy-related problems(TRP)[4 items],therapy setting(TS)[3 items];treatment costs(TC)[2 items].Items are rated on a 7-point Likert-type scale ranging from 1:"Extremely bad" to 7:"Extremely good".Total scores=0 to 100,higher scores=highest possible satisfaction with factors such as independence,therapy convenience,social/school/work activities;health and travel costs.As pre-specified in protocol, data is reported as per age (2-13 years and >=14 years).All-Treated Set included all enrolled participants of age group ‘2-13 years’ and ‘>=14 years’ who received at least 1 dose of study drug (IGIV or IGSC).‘n’=Number analysed are participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline up to end of the study (approximately 1.5 years)

End point values	Age 2-13years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg	Age ≥14 years:Epoch 1+2+3[IGIV200-600+IGSC50-100+100-400]mg/kg
Number of subjects analysed	6	11
Units: score on a scale
arithmetic mean (standard deviation)
IGIV:Epoch 1:Baseline(Week 1):Factor 1 TI(n=6,11)	81.48 ( 14.873 )	77.02 ( 17.963 )
IGIV:Epoch1:Baseline(Week1):Factor 1 TRP(n=6,11)	81.94 ( 15.516 )	79.17 ( 15.811 )
IGIV:Epoch 1:Baseline(Week 1):Factor 1 TS(n=6,11)	77.78 ( 20.488 )	74.75 ( 23.748 )
IGIV:Epoch 1:Baseline(Week 1):Factor 1 TC(n=6,11)	65.28 ( 24.391 )	53.79 ( 21.847 )
IGSC: Epoch 2: CFB (Week 1): Factor 1 TI(n=6,11)	-8.33 ( 21.445 )	-2.53 ( 14.351 )
IGSC: Epoch 2: CFB (Week 1): Factor 1 TRP(n=6,11)	2.78 ( 9.742 )	-1.52 ( 15.841 )
IGSC: Epoch 2: CFB (Week 1): Factor 1 TS(n=6,11)	-6.48 ( 30.106 )	0.51 ( 11.773 )
IGSC: Epoch 2: CFB (Week 1): Factor 1 TC(n=6,11)	-9.72 ( 22.618 )	0.76 ( 31.282 )
IGSC: Epoch 3: CFB (Week 1): Factor 1 TI (n=5,5)	4.17 ( 1.964 )	3.33 ( 4.120 )
IGSC: Epoch 3: CFB (Week 1): Factor 1 TRP (n=5,5)	-14.58 ( 14.731 )	1.67 ( 14.613 )
IGSC: Epoch 3: CFB (Week 1): Factor 1 TS (n=5,5)	19.44 ( 3.928 )	12.22 ( 16.387 )
IGSC: Epoch 3: CFB (Week 1): Factor 1 TC (n=5,5)	0.00 ( 0.000 )	18.33 ( 40.139 )
IGSC:Epoch3:CFB(Week13[EOS/ET]):Factor1 TI(n=6,11)	-2.78 ( 13.494 )	-0.25 ( 13.046 )
IGSC:Epoch3:CFB(Week13[EOS/ET]):Factor1TRP(n=6,11)	-1.39 ( 9.001 )	1.14 ( 9.334 )
IGSC:Epoch3:CFB(Week 13[EOS/ET]):Factor1TS(n=6,11)	2.78 ( 16.005 )	4.55 ( 16.067 )
IGSC:Epoch3:CFB(Week 13[EOS/ET]):Factor1TC(n=6,11)	4.17 ( 16.672 )	14.39 ( 26.898 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose of study drug up to end of treatment (up to Week 57)

Adverse event reporting additional description

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Epoch 1: IGIV 200-600 mg/kg

Reporting group description

Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 or 4 weeks for up to 13 weeks.

Reporting group title

Epoch 3: IGSC (20%) 100-400 mg/kg

Reporting group description

Participants who entered to Epoch 3 from Epoch 2 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.

Reporting group title

Epoch 2: IGSC (20%) 50-200 mg/kg

Reporting group description

Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.

Serious adverse events	Epoch 1: IGIV 200-600 mg/kg	Epoch 3: IGSC (20%) 100-400 mg/kg	Epoch 2: IGSC (20%) 50-200 mg/kg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	0 / 17 (0.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Epoch 1: IGIV 200-600 mg/kg	Epoch 3: IGSC (20%) 100-400 mg/kg	Epoch 2: IGSC (20%) 50-200 mg/kg
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 17 (64.71%)	3 / 7 (42.86%)	16 / 17 (94.12%)
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Occult blood positive
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Seborrhoeic keratosis
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Injury, poisoning and procedural complications
Vaccination complication
subjects affected / exposed	0 / 17 (0.00%)	1 / 7 (14.29%)	1 / 17 (5.88%)
occurrences all number	0	1	2
Ligament sprain
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Wound
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Traumatic arthropathy
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	3 / 17 (17.65%)	1 / 7 (14.29%)	3 / 17 (17.65%)
occurrences all number	7	1	8
Orthostatic intolerance
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Sciatica
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
General disorders and administration site conditions
Injection site swelling
subjects affected / exposed	0 / 17 (0.00%)	1 / 7 (14.29%)	3 / 17 (17.65%)
occurrences all number	0	1	7
Injection site erythema
subjects affected / exposed	0 / 17 (0.00%)	1 / 7 (14.29%)	3 / 17 (17.65%)
occurrences all number	0	1	4
Injection site pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	2 / 17 (11.76%)
occurrences all number	0	0	2
Pyrexia
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	2
Administration site discolouration
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Vaccination site pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	2 / 17 (11.76%)
occurrences all number	0	0	2
Administration site pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	3
Administration site swelling
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Chills
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Infusion site bruising
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Infusion site erythema
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	4
Infusion site pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Infusion site pruritus
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	4
Infusion site swelling
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	7
Injection site bruising
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Vaccination site joint erythema
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Puncture site pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Malaise
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	2
Injection site reaction
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Eye disorders
Myopia
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Gastrointestinal disorders
Stomatitis
subjects affected / exposed	3 / 17 (17.65%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	4	0	1
Dental caries
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Diarrhoea
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	2	0	1
Nausea
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Constipation
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Toothache
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Haemorrhoids
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Eczema asteatotic
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Dermatitis atopic
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Miliaria
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Rash pruritic
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Seborrhoeic dermatitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Urticaria
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	2 / 17 (11.76%)
occurrences all number	0	0	2
Arthritis
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Pain in jaw
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Back pain
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	2	0	0
Infections and infestations
Conjunctivitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	2 / 17 (11.76%)
occurrences all number	1	0	2
Nasopharyngitis
subjects affected / exposed	2 / 17 (11.76%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	2	0	2
Gastroenteritis
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	2 / 17 (11.76%)
occurrences all number	0	0	2
Sinusitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	2 / 17 (11.76%)
occurrences all number	0	0	3
Upper respiratory tract infection
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Bronchitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Cystitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Hordeolum
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Impetigo
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Laryngitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Oral herpes
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Otitis externa
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Parotitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Pharyngitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Periodontitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 7 (0.00%)	0 / 17 (0.00%)
occurrences all number	1	0	0
Pneumonia
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1
Pulpitis dental
subjects affected / exposed	0 / 17 (0.00%)	0 / 7 (0.00%)	1 / 17 (5.88%)
occurrences all number	0	0	1

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Open-label, Non-controlled, Multi-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Subjects with Primary Immunodeficiency Diseases (PID)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2

Primary: Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2

Primary: Epoch 3: Total Serum Trough Levels of IgG Antibodies

Primary: Epoch 3: Total Serum Trough Levels of IgG Antibodies

Secondary: Epoch 1: Total Serum Trough Levels of IgG Antibodies

Secondary: Epoch 1: Total Serum Trough Levels of IgG Antibodies

Secondary: Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG

Secondary: Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG

Secondary: Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG

Secondary: Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG

Secondary: Epoch 2: CL/F for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: CL/F for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG

Secondary: Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG

Secondary: Epoch 2: Cmax for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: Cmax for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG

Secondary: Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG

Secondary: Epoch 2: Cmin for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: Cmin for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG

Secondary: Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG

Secondary: Epoch 2: Tmax for Total Serum Levels of IgG Subclasses

Secondary: Epoch 2: Tmax for Total Serum Levels of IgG Subclasses

Secondary: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)

Secondary: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)

Secondary: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)

Secondary: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)

Secondary: Health Related Quality of Life: Treatment Preference

Secondary: Health Related Quality of Life: Treatment Preference

Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs)

Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs)

Secondary: Number of Participants with Tolerability Events Related to the Infusion of Study Drug

Secondary: Number of Participants with Tolerability Events Related to the Infusion of Study Drug

Secondary: Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)

Secondary: Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)

Secondary: Annual Rate of All Infections Per Year

Secondary: Annual Rate of All Infections Per Year

Secondary: Number of Days Participants not Able to Attend School or Work to Perform Normal Daily Activities due to Illness/Infection

Secondary: Number of Days Participants not Able to Attend School or Work to Perform Normal Daily Activities due to Illness/Infection

Secondary: Number of Days Participants Were on Antibiotics

Secondary: Number of Days Participants Were on Antibiotics

Secondary: Number of Participants Hospitalized due to Illness or Infection

Secondary: Number of Participants Hospitalized due to Illness or Infection

Secondary: Length of Hospital Stay

Secondary: Length of Hospital Stay

Secondary: Number of Acute Physician Visits due to Illness/Infection

Secondary: Number of Acute Physician Visits due to Illness/Infection

Secondary: Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score

Secondary: Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score

Secondary: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score

Secondary: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score

Secondary: Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score

Secondary: Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score

Secondary: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score

Secondary: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score

Secondary: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score

Secondary: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Open-label, Non-controlled, Multi-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Subjects with Primary Immunodeficiency Diseases (PID)