Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy

• Sponsor: CSL Behring (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00419341
• Collaborator: (none)
• Enrollment: 49
• Locations: 13
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Deficiency	Biological: Human Normal Immunoglobulin for Subcutaneous Administration	Phase 3

Detailed Description

The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Open-Label, Prospective, Multicenter Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human), IgPro20 in Subjects With Primary Immunodeficiency (PID)
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: IgPro20 Human Normal Immunoglobulin for Subcutaneous Administration (IgPro20) is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator.

Biological: Human Normal Immunoglobulin for Subcutaneous Administration; Other Names: Hizentra

Outcome Measures

Primary Outcome Measures

1. Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population) [Efficacy period: up to 12 months (week 13 to the completion visit)]

   The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.

2. Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG) [Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment]

   Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR [NCT00168025] or ZLB05_006CR [NCT00322556]).

Secondary Outcome Measures

1. Annualized Rate of Clinically Documented SBIs (ITT Population) [For the duration of the study, up to 15 months]

   The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.

2. Annualized Rate of Clinically Documented SBIs (PPE Population) [Efficacy period: up to 12 months (week 13 to the completion visit)]

   The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.

3. Annualized Rate of Infection Episodes [Efficacy period: up to 12 months (week 13 to completion visit)]

   The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

4. Number of Infection Episodes (Serious and Non-serious) [Efficacy period: up to 12 months (week 13 to the completion visit)]

   Total number of infections for the specified analysis population

5. Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections [Efficacy period: up to 12 months (week 13 to the completion visit)]

   The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

6. Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections [Efficacy period: up to 12 months (week 13 to the completion visit)]

   Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population

7. Annualized Rate of Hospitalization Due to Infection [Efficacy period: up to 12 months (week 13 to the completion visit)]

   The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

8. Number of Days of Hospitalization Due to Infections [Efficacy period: up to 12 months (week 13 to the completion visit)]

   Total number of days of hospitalization due to infections for the specified analysis population

9. Use of Antibiotics for Infection Prophylaxis and Treatment [Efficacy period: up to 12 months (week 13 to the completion visit)]

   Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.

10. Total Serum IgG Trough Levels [Every 4 weeks, throughout the 12-month efficacy period]

    The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.

11. Maximum Concentration (Cmax) of Total Serum IgG at Steady State [Week 28 ± 1 week of the treatment period]

12. Tmax at Steady State [Week 28 ± 1 week of the treatment period]

    Timepoint of maximum concentration (Cmax)

Other Outcome Measures

1. Minimum Concentration (Cmin) of Total Serum IgG at Steady State [Week 28 ± 1 week of the treatment period]

2. Rate of All AEs by Relatedness and Seriousness [For the duration of the study, up to 15 months]

   The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.

3. Rate of Mild, Moderate, or Severe Local Reactions [For the duration of the study, up to 15 months]

   In addition to the standard MedDRA System Organ Class (SOC) AE assignments, the category of 'local reactions' was defined to provide the possibility for a combined analysis of local reactions and included AEs of injection site reaction, injection site bruising, infusion site scab, injection site cyst, injection site eczema, injection site irritation, injection site nodule, and injection site pain. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female aged 2 to 75 years

• Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia)

• Written informed consent

Exclusion Criteria:

• Newly diagnosed PID

• Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis)

• Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma

• Known hyperprolinemia

• Hypoalbuminemia, protein-losing enteropathies, and any proteinuria

• Allergic reactions to immunoglobulins or other blood products

• Known antibodies to Immunoglobulin A (IgA)

• The subject is receiving steroids (oral and parenteral, daily ≥ 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants

• Female who is pregnant, breast feeding or planning a pregnancy during the course of the study

• Participation in a study with an investigational product other than (IVIG) within 1 month prior to enrollment

• A positive result at screening on any of the following viral markers: Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV)

• Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration > 2.5 times the upper normal limit (UNL)

• Creatinine concentration > 1.5 times the UNL

• Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site	Los Angeles	California	United States	90025
2	Study Site	Los Angeles	California	United States	90027
3	Study Site	Centennial	Colorado	United States	80112
4	Study Site	North Palm Beach	Florida	United States	33408
5	Study Site	Atlanta	Georgia	United States	30322
6	Study Site	Fort Wayne	Indiana	United States	46815
7	Study Site	Indianapolis	Indiana	United States	46202
8	Study Site	Iowa City	Iowa	United States	52242
9	Study Site	St.Louis	Missouri	United States	63104-1095
10	Study Site	Newark	New Jersey	United States	07103
11	Study Site	New York	New York	United States	10029
12	Study Site	Philadelphia	Pennsylvania	United States	19104
13	Study Site	Dallas	Texas	United States	75230

Sponsors and Collaborators

• CSL Behring

Investigators

• Principal Investigator: Richard L. Wasserman, MD, PhD, Dallas Allergy Immunology and Medical City Children's Hospital,

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT00419341
• Other Study ID Numbers: ZLB04_009CR; 1458
• First Posted: Jan 8, 2007
• Last Update Posted: Jan 25, 2013
• Last Verified: Dec 1, 2012

• Keywords provided by CSL Behring: Immune globulin subcutaneous; SCIG; Primary immunodeficiency; PID
• Additional relevant MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies

Study Results

Participant Flow

Recruitment Details	A total of 12 centers in the United States enrolled subjects for this study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Period Title: Wash in/Wash Out Period
STARTED	49
COMPLETED	38
NOT COMPLETED	11
Period Title: Wash in/Wash Out Period
STARTED	38
COMPLETED	28
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Overall Participants	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.4 (20.09)
Age, Customized (participants) [Number]
2 to < 12 years	3 6.1%
12 to < 16 years	7 14.3%
16 to < 65 years	33 67.3%
≥ 65 years	6 12.2%
Sex: Female, Male (Count of Participants)
Female	27 55.1%
Male	22 44.9%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	3 6.1%
White	46 93.9%
Type of Primary Immunodeficiency (participants) [Number]
Common variable immunodeficiency (CVID)	46 (21.24) 93.9%
X-linked agammaglobulinemia (XLA)	3 6.1%

Outcome Measures

1. Primary Outcome

Title	Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
Description	The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (MITT) population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Measure Efficacy Period Subject Study Days	12697
Number [SBIs per subject year]	0.00

2. Primary Outcome

Title	Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)
Description	Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR [NCT00168025] or ZLB05_006CR [NCT00322556]).
Time Frame	Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment

Outcome Measure Data

Analysis Population Description

The Per Protocol Pharmacokinetic (PPK) population included all subjects with the disease under study who fulfilled the requirements of the PK substudy, including PK sampling in a preceding study with IVIG (Privigen, CSL Behring), and fulfilling IgPro20 dosing requirements and providing adequate PK blood samples in the current study.

Arm/Group Title	IgPro20 (PK Substudy)	IVIG (Privigen; Previous Study)
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.	Privigen is a liquid formulation of normal human IgG at a concentration of 10% administered as an intravenous infusion every 3 or 4 weeks.
Measure Participants	18	18
Mean (Standard Deviation) [days*g/L]	105.6 (31.56)	103.2 (20.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IgPro20, IVIG (Privigen; Previous Study)
	Comments	Individual sAUC values (standardized to a 7-day period) of the IV and adjusted SC sampling periods in each individual subject were log transformed and a parametric 2-sided 90% confidence interval (CI) for the mean of the individual differences was obtained. Back-transformation of the mean and its CI produced the geometric mean ratio (GMR) and its respective 90% CI.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority of SCIG:IVIG treatment was concluded if the lower GMR confidence limit was 0.8 or more. With 18 evaluable subjects, the power to show this non-inferiority was calculated to be 85% based on the assumptions of an intra-individual variability with a coefficient of variation (CV) = 25% and a GMR equal to or greater than 1.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio (GMR)
	Estimated Value	1.002
	Confidence Interval	(2-Sided) 90%; 0.951 to 1.055
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio SCIG:IVIG non-inferiority was concluded if the lower GMR confidence limit was 0.8 or more

3. Secondary Outcome

Title	Annualized Rate of Clinically Documented SBIs (ITT Population)
Description	The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Time Frame	For the duration of the study, up to 15 months

Outcome Measure Data

Analysis Population Description

The Intention To Treat (ITT) population included all subjects who were treated with IgPro20 during any study period.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	49
Measure Subject Study Days	16234
Number [SBIs per subject year]	0.00

4. Secondary Outcome

Title	Annualized Rate of Clinically Documented SBIs (PPE Population)
Description	The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The Per Protocol Efficacy (PPE) population included all subjects who completed the 12-month efficacy period according to the protocol-defined requirements.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	25
Measure Efficacy Period Subject Study Days	9543
Number [SBIs per subject year]	0.00

5. Secondary Outcome

Title	Annualized Rate of Infection Episodes
Description	The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time Frame	Efficacy period: up to 12 months (week 13 to completion visit)

Outcome Measure Data

Analysis Population Description

The MITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Measure Subject Study Days	12697
Number (95% Confidence Interval) [infection episodes per subject year]	2.76

6. Secondary Outcome

Title	Number of Infection Episodes (Serious and Non-serious)
Description	Total number of infections for the specified analysis population
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The MITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Number [infections]	96

7. Secondary Outcome

Title	Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Description	The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (MITT) population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Measure Exposure Days	12605
Number [days per subject year]	2.06

8. Secondary Outcome

Title	Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Description	Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The MITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Number [days]	71

9. Secondary Outcome

Title	Annualized Rate of Hospitalization Due to Infection
Description	The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The MITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Measure Exposure Days	12605
Number [days per subject year]	0.20

10. Secondary Outcome

Title	Number of Days of Hospitalization Due to Infections
Description	Total number of days of hospitalization due to infections for the specified analysis population
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The MITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Number [days]	7

11. Secondary Outcome

Title	Use of Antibiotics for Infection Prophylaxis and Treatment
Description	Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.
Time Frame	Efficacy period: up to 12 months (week 13 to the completion visit)

Outcome Measure Data

Analysis Population Description

The MITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Measure Exposure Days	12697
Number [days per subject year]	48.52

12. Secondary Outcome

Title	Total Serum IgG Trough Levels
Description	The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
Time Frame	Every 4 weeks, throughout the 12-month efficacy period

Outcome Measure Data

Analysis Population Description

The MITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with week 13) who had the disease under study.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	38
Mean (Standard Deviation) [g/L]	12.53 (3.21)

13. Secondary Outcome

Title	Maximum Concentration (Cmax) of Total Serum IgG at Steady State
Time Frame	Week 28 ± 1 week of the treatment period

Outcome Measure Data

Analysis Population Description

The PPK population included all subjects with the disease under study who fulfilled the requirements of the PK substudy, including PK sampling in a preceding study with IVIG (Privigen, CSL Behring), and fulfilling IgPro20 dosing requirements and providing adequate PK blood samples in the current study.

Arm/Group Title	IgPro20 (PK Substudy)
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	18
Mean (Standard Deviation) [g/L]	16.16 (4.93)

14. Secondary Outcome

Title	Tmax at Steady State
Description	Timepoint of maximum concentration (Cmax)
Time Frame	Week 28 ± 1 week of the treatment period

Outcome Measure Data

Analysis Population Description

The PPK population included all subjects with the disease under study who fulfilled the requirements of the PK substudy, including PK sampling in a preceding study with IVIG (Privigen, CSL Behring), and fulfilling IgPro20 dosing requirements and providing adequate PK blood samples in the current study.

Arm/Group Title	IgPro20 (PK Substudy)
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	18
Median (Full Range) [days]	3.118 (1.7729)

15. Other Pre-specified Outcome

Title	Minimum Concentration (Cmin) of Total Serum IgG at Steady State
Time Frame	Week 28 ± 1 week of the treatment period

Outcome Measure Data

Analysis Population Description

The PPK population included all subjects with the disease under study who fulfilled the requirements of the PK substudy, including PK sampling in a preceding study with IVIG (Privigen, CSL Behring), and fulfilling IgPro20 dosing requirements and providing adequate PK blood samples in the current study.

Arm/Group Title	IgPro20 (PK Substudy)
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	18
Mean (Standard Deviation) [g/L]	13.70 (4.39)

16. Other Pre-specified Outcome

Title	Rate of All AEs by Relatedness and Seriousness
Description	The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.
Time Frame	For the duration of the study, up to 15 months

Outcome Measure Data

Analysis Population Description

The ITT population included all subjects who were treated with IgPro20 during any study period.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	49
Measure Infusions	2264
All	0.773
At least possibly related	0.634
Serious	0.004
At least possibly related and serious	0

17. Other Pre-specified Outcome

Title	Rate of Mild, Moderate, or Severe Local Reactions
Description	In addition to the standard MedDRA System Organ Class (SOC) AE assignments, the category of 'local reactions' was defined to provide the possibility for a combined analysis of local reactions and included AEs of injection site reaction, injection site bruising, infusion site scab, injection site cyst, injection site eczema, injection site irritation, injection site nodule, and injection site pain. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.
Time Frame	For the duration of the study, up to 15 months

Outcome Measure Data

Analysis Population Description

The ITT population included all subjects who were treated with IgPro20 during any study period.

Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
Measure Participants	49
Measure Infusions	2264
All	0.592
Mild	0.553
Moderate	0.038
Severe	0.002

Adverse Events

Time Frame	Approximately 15 months (including the 3 month wash in/wash out period and the 12 month efficacy period).
Adverse Event Reporting Description	For the serious AEs (SAEs), treatment-emergent SAEs are provided.
Arm/Group Title	IgPro20
Arm/Group Description	IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals.
All Cause Mortality
	IgPro20
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IgPro20
	Affected / at Risk (%)	# Events
Total	7/49 (14.3%)
Gastrointestinal disorders
Small intestinal obstruction	1/49 (2%)	1
General disorders
Chest pain	2/49 (4.1%)	2
Infections and infestations
Gastroenteritis	1/49 (2%)	1
Tooth abscess	1/49 (2%)	1
Cellulitis	1/49 (2%)	1
Urinary tract infection	1/49 (2%)	1
Investigations
Haemoglobin decreased	1/49 (2%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	1/49 (2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer	1/49 (2%)	1
Other (Not Including Serious) Adverse Events
	IgPro20
	Affected / at Risk (%)	# Events
Total	49/49 (100%)
Ear and labyrinth disorders
Ear pain	3/49 (6.1%)	3
Eye disorders
Conjunctivitis	3/49 (6.1%)	3
Gastrointestinal disorders
Diarrhoea	7/49 (14.3%)	8
Abdominal pain upper	5/49 (10.2%)	5
Nausea	5/49 (10.2%)	5
Vomiting	3/49 (6.1%)	3
General disorders
Injection site reaction	49/49 (100%)	1314
Fatigue	6/49 (12.2%)	6
Injection site bruising	5/49 (10.2%)	19
Pain	4/49 (8.2%)	5
Infections and infestations
Sinusitis	14/49 (28.6%)	20
Nasopharyngitis	11/49 (22.4%)	15
Bronchitis	6/49 (12.2%)	9
Acute sinusitis	5/49 (10.2%)	7
Upper respiratory tract infection	5/49 (10.2%)	6
Urinary tract infection	3/49 (6.1%)	3
Viral infection	4/49 (8.2%)	7
Influenza	3/49 (6.1%)	3
Otitis media	3/49 (6.1%)	5
Injury, poisoning and procedural complications
Contusion	3/49 (6.1%)	4
Musculoskeletal and connective tissue disorders
Back pain	5/49 (10.2%)	11
Arthralgia	4/49 (8.2%)	5
Pain in extremity	4/49 (8.2%)	7
Myalgia	3/49 (6.1%)	4
Nervous system disorders
Headache	13/49 (26.5%)	40
Migraine	4/49 (8.2%)	5
Psychiatric disorders
Insomnia	3/49 (6.1%)	3
Respiratory, thoracic and mediastinal disorders
Cough	8/49 (16.3%)	9
Epistaxis	4/49 (8.2%)	6
Pharyngolaryngeal pain	4/49 (8.2%)	6
Asthma	3/49 (6.1%)	6
Skin and subcutaneous tissue disorders
Rash	5/49 (10.2%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requests that reports based on single-site data not precede the primary publication of the entire clinical trial.