Trial Outcomes & Findings for A Phase 3 Study Evaluating Safety and Effectiveness of Immune Globulin Intravenous (IGIV 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease (NCT NCT00818662)

Last Updated: 2021-05-19

Results Overview

The ADAS-Cog is a validated psychometric instrument that evaluates memory (word recall, word recognition), attention, reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). This test was administered by experienced raters certified by Alzheimer's Disease Cooperative Study (ADCS) at each site. Scores on the ADAS-Cog range from 0-70 with higher scores indicating greater impairment; hence increases from baseline reflect potential cognitive deterioration.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

390 participants

Primary outcome timeframe

Baseline & 18 months

Results posted on

2021-05-19

Participant Flow

Recruitment was conducted in the U.S., and Canada, at 45 study sites. The first participant was enrolled in December 2008.

702 participants were enrolled; 308 were screen failures; 4 were discontinued before randomization; and 7 were withdrawn after randomization, but prior to receiving investigational product. Therefore 383 participants were randomized.

Participant milestones

Participant milestones
Measure	IGIV, 10% 400mg/kg Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks	IGIV, 10% 200mg/kg Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks	Placebo 4 mL/kg 0.25% human albumin solution infused at 4 mL/kg/2weeks Placebo solution: 4 mL/kg : 0.25% human albumin solution infused at 4 mL/kg/2weeks for 70 weeks	Placebo 2 mL/kg 0.25% human albumin solution infused at 2 mL/kg/2weeks Placebo solution: 2 mL/kg : 0.25% human albumin solution infused at 2 mL/kg/2weeks for 70 weeks
Overall Study STARTED	127	135	58	63
Overall Study COMPLETED	104	102	49	47
Overall Study NOT COMPLETED	23	33	9	16

Reasons for withdrawal

Reasons for withdrawal
Measure	IGIV, 10% 400mg/kg Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks	IGIV, 10% 200mg/kg Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks	Placebo 4 mL/kg 0.25% human albumin solution infused at 4 mL/kg/2weeks Placebo solution: 4 mL/kg : 0.25% human albumin solution infused at 4 mL/kg/2weeks for 70 weeks	Placebo 2 mL/kg 0.25% human albumin solution infused at 2 mL/kg/2weeks Placebo solution: 2 mL/kg : 0.25% human albumin solution infused at 2 mL/kg/2weeks for 70 weeks
Overall Study Adverse Event	5	14	4	3
Overall Study Withdrawal by Subject	5	4	2	2
Overall Study Death	1	3	0	0
Overall Study Physician Decision	1	0	0	0
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Unwilling or Unable to Participate	4	6	2	4
Overall Study Protocol Violation	1	1	0	0
Overall Study Requires a Prohibited Medication	1	0	0	0
Overall Study Safety Risk	1	1	0	1
Overall Study Study Partner Unwilling or Unable	3	2	1	1
Overall Study Participant's health declined	0	0	0	1
Overall Study Caregiver to pursue other treatment	0	1	0	0
Overall Study Moving out of state	0	0	0	1
Overall Study Declined move to another study site	1	0	0	0
Overall Study Change in living situation	0	0	0	1
Overall Study Study partner decision	0	0	0	1
Overall Study Admitted to long term nursing care	0	1	0	0

Baseline Characteristics

A Phase 3 Study Evaluating Safety and Effectiveness of Immune Globulin Intravenous (IGIV 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks	Placebo 4 mL/kg n=58 Participants 0.25% human albumin solution infused at 4 mL/kg/2weeks Placebo solution: 4 mL/kg : 0.25% human albumin solution infused at 4 mL/kg/2weeks for 70 weeks	Placebo 2 mL/kg n=63 Participants 0.25% human albumin solution infused at 2 mL/kg/2weeks Placebo solution: 2 mL/kg : 0.25% human albumin solution infused at 2 mL/kg/2weeks for 70 weeks	Total n=383 Participants Total of all reporting groups
Age, Continuous	70.5 years STANDARD_DEVIATION 9.6 • n=5 Participants	70.1 years STANDARD_DEVIATION 8.3 • n=7 Participants	70.3 years STANDARD_DEVIATION 9.7 • n=5 Participants	70.1 years STANDARD_DEVIATION 10.3 • n=4 Participants	70.3 years STANDARD_DEVIATION 9.3 • n=21 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	74 Participants n=7 Participants	33 Participants n=5 Participants	33 Participants n=4 Participants	209 Participants n=21 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	61 Participants n=7 Participants	25 Participants n=5 Participants	30 Participants n=4 Participants	174 Participants n=21 Participants
Region of Enrollment United States	117 Participants n=5 Participants	127 Participants n=7 Participants	56 Participants n=5 Participants	58 Participants n=4 Participants	358 Participants n=21 Participants
Region of Enrollment Canada	10 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	25 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline & 18 months

Population: Intent-to-Treat Analysis Set with both baseline and month 18 assessments.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=105 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=100 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=95 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)	7.4 Scores on a scale Standard Deviation 7.95	8.9 Scores on a scale Standard Deviation 8.20	8.4 Scores on a scale Standard Deviation 9.37

PRIMARY outcome

Timeframe: Baseline & 18 Months

Population: Intent-to-Treat Analysis Set with both baseline and month 18 assessments.

The ADCS-ADL scale is a validated tool to assess instrumental and basic activities of daily living based on a 23 item structured interview of the caregiver or qualified study partner. Scores on the ADCS-ADL range from 0-78 with lower scores indicating greater impairment; hence decreases from baseline reflect potential functional deterioration.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=104 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=102 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=95 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)	-11.4 Scores on a scale Standard Deviation 10.49	-12.4 Scores on a scale Standard Deviation 11.41	-11.4 Scores on a scale Standard Deviation 12.19

SECONDARY outcome

Timeframe: Baseline & 9 months

Population: Intent-to-Treat Analysis Set with both baseline and month 9 assessments.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=114 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=114 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=106 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 9 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)	2.7 Scores on a scale Standard Deviation 5.20	4.5 Scores on a scale Standard Deviation 6.16	3.5 Scores on a scale Standard Deviation 6.44

SECONDARY outcome

Timeframe: Baseline & 9 Months

Population: Intent-to-Treat Analysis Set with both baseline and month 9 assessments.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=111 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=116 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=107 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 9 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)	-5.4 Scores on a scale Standard Deviation 7.03	-6.1 Scores on a scale Standard Deviation 8.13	-5.8 Scores on a scale Standard Deviation 8.32

SECONDARY outcome

Timeframe: Baseline & 9 Months

Population: Intent-to-Treat Analysis Set with both baseline and month 9 assessments.

The ADCS-CGIC is a validated categorical measure of change in a participant's clinical condition between baseline and follow-up visits; it is used to assess global clinical status. The ADCS CGIC score is based on direct examination of the participant and an interview of the caregiver. The rater should refer to the baseline ADCS-CGIC worksheets in making a rating. A skilled and experienced clinician who is blinded to treatment assignment rates the participant on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). 1= Very much better 2= Much better 3= A little better 4= Same 5= A little worse 6= Much worse 7= Very much worse

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=114 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=114 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=104 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 9: Much better (2)	2 participants	1 participants	1 participants
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 9: Very much worse (7)	1 participants	3 participants	0 participants
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 9: Much worse (6)	19 participants	18 participants	12 participants
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 9: Very much better (1)	0 participants	0 participants	0 participants
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 9: A little better (3)	7 participants	3 participants	7 participants
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 9: Same (4)	33 participants	33 participants	36 participants
Change From Baseline at 9 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 9: A little worse (5)	52 participants	56 participants	48 participants

SECONDARY outcome

Timeframe: Baseline & 18 Months

Population: Intent-to-Treat Analysis Set with both baseline and month 18 assessments.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=105 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=101 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=92 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 18: Very much better (1)	0 participants	0 participants	0 participants
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 18: A little better (3)	6 participants	1 participants	3 participants
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 18: Same (4)	15 participants	15 participants	16 participants
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 18: A little worse (5)	44 participants	43 participants	36 participants
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 18: Much worse (6)	32 participants	33 participants	32 participants
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 18: Very much worse (7)	7 participants	7 participants	4 participants
Change From Baseline at 18 Months in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Assessment Month 18: Much better (2)	1 participants	2 participants	1 participants

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Intent-to-Treat Analysis Set with both baseline and month 18 assessments.

The 3MS is a comprehensive validated instrument that provides a 100 point composite rating for spatial and temporal orientation, verbal recall, simple attention, working memory, naming, repetition, comprehension, writing and constructional abilities. Scores range from 0 to 100 with lower values indicating greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=103 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=102 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=91 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Modified Mini-Mental State Examination (3MS) Examination	-12.1 Scores on a scale Standard Deviation 13.12	-15.3 Scores on a scale Standard Deviation 12.76	-13.5 Scores on a scale Standard Deviation 10.95

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Intent-to-Treat Analysis Set with both baseline and month 18 assessments.

The NPI is a validated instrument used to assess behavioral psychopathology in AD; it evaluates the frequency and severity of 12 neuropsychiatric features including delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, aberrant motor activity, sleep and night-time behavior change, and appetite and eating change. The NPI total score ranged 0-144, with higher scores indicating greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=104 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=102 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=94 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Neuropsychiatric Inventory (NPI) Assessment	3.7 Scores on a scale Standard Deviation 12.93	4.9 Scores on a scale Standard Deviation 13.30	2.4 Scores on a scale Standard Deviation 10.77

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Intent-to-Treat Analysis Set with both baseline and month 18 assessments.

The QOL AD is a validated, 13-item instrument developed specifically for individuals with dementia. The assessment rates the participant's quality of life for physical, emotional, interpersonal, and environmental domains. The QOL-AD total score ranged 13-52. Lower scores on the QOL AD are associated with a lower quality of life.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=99 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=99 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=86 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Participant Response	-0.5 Scores on a scale Standard Deviation 5.34	-0.7 Scores on a scale Standard Deviation 4.40	-1.5 Scores on a scale Standard Deviation 5.20

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Intent-to-Treat Analysis Set with both baseline and month 18 assessments.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=99 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=99 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=92 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Logsdon Quality of Life in Alzheimer's Disease (QOL-AD) Assessment- Caregiver Response	-3.0 Scores on a scale Standard Deviation 4.97	-2.5 Scores on a scale Standard Deviation 5.17	-1.6 Scores on a scale Standard Deviation 5.12

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

This test assesses working memory and attention, the rater asks the participant to repeat single-digit number sequences of increasing length, which are read aloud by the rater (in forward or backward order). Two trials are presented for each sequence length, and the test is ended when the participant misses both trials at a given sequence length. The WAIS-R score ranged from 0-14. Results are presented as total number correct; therefore, lower numbers represent greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=97 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=93 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=88 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Forward	-0.8 correct responses Standard Deviation 2.00	-1.2 correct responses Standard Deviation 2.21	-1.1 correct responses Standard Deviation 1.81

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=94 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=89 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=86 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Span Backward	-0.8 correct responses Standard Deviation 1.95	-1.2 correct responses Standard Deviation 1.88	-1.2 correct responses Standard Deviation 1.79

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

In the FAS assessment of phenomic verbal fluency, participants are given 1 minute each to name as many words as they can that begin with a specified letter (F, A, S). To receive credit, words must be verifiable in a dictionary, cannot be proper nouns, and cannot be the same word or variations of the same word (e.g., the same word with a different ending, such as 'acts,' 'acted,' 'acting'). Results are presented as total number correct; therefore, lower numbers indicate greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=96 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=91 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=85 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: FAS Verbal Fluency	-4.7 correct responses Standard Deviation 8.60	-7.4 correct responses Standard Deviation 9.00	-6.3 correct responses Standard Deviation 8.17

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

WAIS-R digit symbol substitution test assesses attention, psychomotor speed, complex scanning, visual tracking, and immediate memory. This test consists of 4 rows each with 25 small blank squares; above each square is a number between 1 and 9. At the top is a 'key,' which pairs each number (1 through 9) with an unfamiliar symbol. The participant has 90 seconds to work as quickly as possible (left to right across the rows) to fill in each blank square with the appropriate symbol based on the number above the square. Results are presented as total number correct; therefore, lower numbers indicate greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=80 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=63 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=67 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Wechsler Adult Intelligence Scale- Revised (WAIS-R) Digit Symbol Substitution	-6.8 correct responses Standard Deviation 10.61	-7.7 correct responses Standard Deviation 9.67	-6.2 correct responses Standard Deviation 7.34

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

In this test, which assesses semantic verbal fluency, participants are given 1 minute to name as many items in the category "animals" as possible. To receive credit that word cannot be a mythical animal, but can be an animal species; breed; male, female, or infant name for a species (e.g., bull, cow, calf); in addition, names for birds, fish, reptiles, and insects receive credit. Results are presented as total number correct; therefore, lower numbers indicate greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=97 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=92 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=87 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Animals Category Fluency	-2.8 correct responses Standard Deviation 4.06	-2.2 correct responses Standard Deviation 6.84	-2.7 correct responses Standard Deviation 3.82

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

This test, which has 2 parts, is used to assess processing speed, visuomotor and perceptual scanning skills, and executive function. In Part A, 25 circles each containing a number between 1 and 25 are randomly placed on a sheet of paper, and the participant is asked to draw a line as quickly as possible between each circle in ascending numerical order. In Part B, 25 circles are again randomly placed on a sheet of paper; however, in this test 13 of the circles contain the numbers 1 through 13, and the remaining 12 circles contain the letters A through L. In this test, the participant must draw a line as quickly as possible between the circles in alternating between numbers and letters in ascending order (e.g., 1 to A, A to 2, 2 to B,…). Total values for TMT Part A range between 0 and 150 seconds. Results are presented as time to complete; therefore, higher numbers indicate greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=83 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=75 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=74 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part A	21.6 seconds Standard Deviation 36.93	20.5 seconds Standard Deviation 30.61	21.3 seconds Standard Deviation 35.50

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

This test, which has 2 parts, is used to assess processing speed, visuomotor and perceptual scanning skills, and executive function. In Part A, 25 circles each containing a number between 1 and 25 are randomly placed on a sheet of paper, and the participant is asked to draw a line as quickly as possible between each circle in ascending numerical order. In Part B, 25 circles are again randomly placed on a sheet of paper; however, in this test 13 of the circles contain the numbers 1 through 13, and the remaining 12 circles contain the letters A through L. In this test, the participant must draw a line as quickly as possible between the circles in alternating between numbers and letters in ascending order (e.g., 1 to A, A to 2, 2 to B,…). Total values for TMT Part B range between 0 and 300 seconds. Results are presented as time to complete; therefore, higher numbers indicate greater impairment.

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=61 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=51 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=50 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Trail-Making Test (TMT), Part B	13.0 seconds Standard Deviation 60.49	28.4 seconds Standard Deviation 65.01	31.9 seconds Standard Deviation 66.32

SECONDARY outcome

Timeframe: Baseline & 18 months

Population: Per-Protocol Analysis Set with both baseline and month 18 assessments.

In this test, which assesses constructional ability, visuoperception, and executive functioning, the participant is given a blank sheet of paper and asked to draw the face of a clock showing the numbers and 2 hands set to 'ten after eleven.' Results are presented as score obtained (range 0 to 5, with 0 indicating the greatest impairment).

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=94 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=90 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=85 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Change From Baseline at 18 Months in the Adjunct Neuropsychological Testing: Clock Drawing Test	-0.7 Scores on a scale Standard Deviation 1.27	-0.7 Scores on a scale Standard Deviation 1.15	-0.6 Scores on a scale Standard Deviation 1.17

SECONDARY outcome

Timeframe: Throughout the study period, approximately 4 years

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=121 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Infections and Infestations	1 participants	1 participants	1 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Injury, Poisoning, and Procedural Complications	5 participants	1 participants	0 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Investigations	15 participants	16 participants	13 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Blood and Lymphatic System Disorders	7 participants	2 participants	1 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Cardiac Disorders	1 participants	0 participants	4 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Eye Disorders	1 participants	1 participants	0 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Gastrointestinal Disorders	10 participants	13 participants	7 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class General Disorders & Administration Site Conditions	22 participants	32 participants	13 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Immune System Disorders	0 participants	1 participants	0 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Metabolism and Nutrition Disorders	0 participants	1 participants	0 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Musculoskeletal and Connective Tissue Disorders	7 participants	5 participants	0 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Nervous System Disorders	33 participants	34 participants	24 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Psychiatric Disorders	5 participants	6 participants	2 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Reproductive System and Breast Disorders	0 participants	1 participants	0 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Respiratory, Thoracic and Mediastinal Disorders	3 participants	4 participants	4 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Skin and Subcutaneous Tissue Disorders	26 participants	20 participants	9 participants
Number of Participants Experiencing Study Product-related Non-serious Adverse Events (Non-SAEs), by System Organ Class Vascular Disorders	10 participants	18 participants	17 participants

SECONDARY outcome

Timeframe: Throughout the study period, approximately 4 years

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=121 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class Investigations	0 participants	2 participants	0 participants
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class Cardiac Disorders	1 participants	0 participants	1 participants
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class General Disorders & Administration Site Conditions	0 participants	0 participants	1 participants
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class Immune System Disorders	0 participants	1 participants	0 participants
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class Nervous System Disorders	1 participants	2 participants	0 participants
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class Psychiatric Disorders	0 participants	1 participants	0 participants
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class Respiratory, Thoracic and Mediastinal Disorders	0 participants	1 participants	1 participants
Number of Participants Experiencing Study Product-related Serious Adverse Events (SAEs), by System Organ Class Vascular Disorders	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Throughout the study period, approximately 4 years

Population: Safety Analysis Set

Related and unrelated non-SAEs

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=121 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Ear and Labyrinth Disorders	4 participants	3 participants	5 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Renal and Urinary Disorders	13 participants	16 participants	12 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Reproductive System and Breast Disorders	5 participants	4 participants	3 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Blood and Lymphatic System Disorders	13 participants	7 participants	5 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Cardiac Disorders	3 participants	11 participants	15 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Endocrine Disorders	1 participants	0 participants	1 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Eye Disorders	14 participants	5 participants	9 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Gastrointestinal Disorders	47 participants	51 participants	36 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class General Disorders & Administration Site Conditions	57 participants	66 participants	52 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Immune System Disorders	1 participants	7 participants	3 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Infections and Infestations	40 participants	46 participants	57 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Injury, Poisoning, and Procedural Complications	36 participants	37 participants	50 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Investigations	37 participants	48 participants	30 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Metabolism and Nutrition Disorders	14 participants	15 participants	16 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Musculoskeletal and Connective Tissue Disorders	40 participants	44 participants	27 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Neoplasms, Benign, Malignant and Unspecified	8 participants	8 participants	13 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Nervous System Disorders	63 participants	73 participants	53 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Psychiatric Disorders	41 participants	49 participants	49 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Respiratory, Thoracic and Mediastinal Disorders	23 participants	35 participants	23 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Skin and Subcutaneous Tissue Disorders	49 participants	52 participants	31 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Social Circumstances	0 participants	1 participants	0 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Surgical and Medical Procedures	8 participants	6 participants	8 participants
Number of Participants Experiencing Any Non-serious Adverse Events (Non-SAEs), by System Organ Class Vascular Disorders	22 participants	30 participants	31 participants

SECONDARY outcome

Timeframe: Throughout the study period, approximately 4 years

Population: Safety Analysis Set

Related and unrelated SAEs

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=121 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Infections and Infestations	2 participants	2 participants	4 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Injury, Poisoning, and Procedural Complications	3 participants	2 participants	2 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Blood and Lymphatic System Disorders	2 participants	0 participants	1 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Cardiac Disorders	5 participants	3 participants	3 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Ear and Labyrinth Disorders	1 participants	0 participants	0 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Gastrointestinal Disorders	5 participants	1 participants	1 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class General Disorders & Administration Site Conditions	2 participants	4 participants	2 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Hepatobiliary Disorders	0 participants	1 participants	1 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Immune System Disorders	0 participants	1 participants	0 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Investigations	1 participants	2 participants	1 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Metabolism and Nutrition Disorders	1 participants	1 participants	2 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Musculoskeletal and Connective Tissue Disorders	2 participants	3 participants	0 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Neoplasms, Benign, Malignant and Unspecified	0 participants	3 participants	3 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Nervous System Disorders	3 participants	6 participants	5 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Psychiatric Disorders	2 participants	4 participants	3 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Renal and Urinary Disorders	0 participants	1 participants	1 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Respiratory, Thoracic and Mediastinal Disorders	1 participants	2 participants	3 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Surgical and Medical Procedures	0 participants	1 participants	1 participants
Number of Participants Experiencing Any Serious Adverse Events (SAEs), by System Organ Class Vascular Disorders	4 participants	0 participants	4 participants

SECONDARY outcome

Timeframe: During or within 72 hours of completion of an infusion

Population: Safety Analysis Set

Refers to non-SAEs and/or SAEs occurring during infusion or within 72 hours of completion of infusion (regardless of causality)

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=3691 Infusions All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Infusions Temporally Associated With Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)	396 Infusions	467 Infusions	349 Infusions

SECONDARY outcome

Timeframe: Throughout the study period, approximately 4 years

Population: Safety Analysis Set

Each adverse event (AE) that was considered related to investigational product (IP) was linked to the most recent infusion administered

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=3883 Infusions Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=3954 Infusions Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=3691 Infusions All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Infusions With Causally Associated Non-serious Adverse Events (Non-SAEs) and/or Serious Adverse Events (SAEs)	225 Infusions	265 Infusions	172 Infusions

SECONDARY outcome

Timeframe: Throughout each infusion period

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=3883 Infusions Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=3954 Infusions Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=3691 Infusions All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Infusions Discontinued, Slowed, or Interrupted Due to an Adverse Event (AE)	48 Adverse events	28 Adverse events	36 Adverse events

SECONDARY outcome

Timeframe: Throughout the study period, approximately 4 years

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=121 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Participants Experiencing a Clinically Significant Decrease in Hemoglobin (>1.5 g/dL) Between Consecutive Visits	31 participants	24 participants	16 participants

SECONDARY outcome

Timeframe: Throughout the study period, approximately 4 years

Population: Safety Analysis Set

Participants requiring systemic therapy or discontinuation from further treatment

Outcome measures

Outcome measures
Measure	IGIV, 10% 400mg/kg n=127 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 Participants Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=121 Participants All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Number of Participants Experiencing a Clinically Significant Rash Rash requiring systemic therapy	19 participants	16 participants	8 participants
Number of Participants Experiencing a Clinically Significant Rash Rash requiring discontinuation from treatment	3 participants	2 participants	0 participants

Adverse Events

IGIV, 10% 400mg/kg

Serious events: 21 serious events

Other events: 112 other events

Deaths: 0 deaths

IGIV, 10% 200mg/kg

Serious events: 32 serious events

Other events: 118 other events

Deaths: 0 deaths

Placebo 2 mL/kg or 4 mL/kg

Serious events: 26 serious events

Other events: 103 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication (by USCD) or 12 months after study completion. Baxter requires a review of results communications (e.g., for confidential information) ≥45 days prior to submission or communication. Baxter may request an additional delay of ≤45 days(e.g., for intellectual property protection)
Publication restrictions are in place

Restriction type: OTHER

Measure	IGIV, 10% 400mg/kg n=127 participants at risk Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 400 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	IGIV, 10% 200mg/kg n=135 participants at risk Immune Globulin Intravenous (Human), 10% (IGIV, 10%) Immune Globulin Intravenous (Human), 10% (IGIV, 10%) : 200 mg/kg bodyweight every 2 weeks for 70 weeks Adverse Events That Occurred During or After Treatment	Placebo 2 mL/kg or 4 mL/kg n=121 participants at risk All participants who received the 2 mL/kg or 4 mL/kg placebo solution Placebo solution: 2 mL/kg or 4 mL/kg : 0.25% human albumin solution infused every 2weeks for 70 weeks Adverse Events That Occurred During or After Treatment
Blood and lymphatic system disorders Anaemia	5.5% 7/127 • Number of events 9 • Throughout the study period of approximately 4 years	2.2% 3/135 • Number of events 3 • Throughout the study period of approximately 4 years	1.7% 2/121 • Number of events 2 • Throughout the study period of approximately 4 years
Cardiac disorders Bradycardia	0.79% 1/127 • Number of events 1 • Throughout the study period of approximately 4 years	3.0% 4/135 • Number of events 4 • Throughout the study period of approximately 4 years	6.6% 8/121 • Number of events 9 • Throughout the study period of approximately 4 years
Gastrointestinal disorders Diarrhoea	14.2% 18/127 • Number of events 23 • Throughout the study period of approximately 4 years	14.1% 19/135 • Number of events 24 • Throughout the study period of approximately 4 years	12.4% 15/121 • Number of events 16 • Throughout the study period of approximately 4 years
Gastrointestinal disorders Nausea	12.6% 16/127 • Number of events 24 • Throughout the study period of approximately 4 years	8.1% 11/135 • Number of events 23 • Throughout the study period of approximately 4 years	8.3% 10/121 • Number of events 16 • Throughout the study period of approximately 4 years
Gastrointestinal disorders Vomiting	9.4% 12/127 • Number of events 16 • Throughout the study period of approximately 4 years	4.4% 6/135 • Number of events 10 • Throughout the study period of approximately 4 years	4.1% 5/121 • Number of events 6 • Throughout the study period of approximately 4 years
General disorders Chills	7.9% 10/127 • Number of events 12 • Throughout the study period of approximately 4 years	11.1% 15/135 • Number of events 33 • Throughout the study period of approximately 4 years	2.5% 3/121 • Number of events 3 • Throughout the study period of approximately 4 years
General disorders Fatigue	7.9% 10/127 • Number of events 11 • Throughout the study period of approximately 4 years	9.6% 13/135 • Number of events 35 • Throughout the study period of approximately 4 years	9.9% 12/121 • Number of events 28 • Throughout the study period of approximately 4 years
General disorders Gait Disturbance	1.6% 2/127 • Number of events 2 • Throughout the study period of approximately 4 years	7.4% 10/135 • Number of events 12 • Throughout the study period of approximately 4 years	2.5% 3/121 • Number of events 3 • Throughout the study period of approximately 4 years
General disorders Infusion Site Extravasation	18.1% 23/127 • Number of events 32 • Throughout the study period of approximately 4 years	11.1% 15/135 • Number of events 18 • Throughout the study period of approximately 4 years	17.4% 21/121 • Number of events 30 • Throughout the study period of approximately 4 years
General disorders Oedema Peripheral	3.9% 5/127 • Number of events 5 • Throughout the study period of approximately 4 years	5.2% 7/135 • Number of events 9 • Throughout the study period of approximately 4 years	5.0% 6/121 • Number of events 7 • Throughout the study period of approximately 4 years
General disorders Pyrexia	5.5% 7/127 • Number of events 8 • Throughout the study period of approximately 4 years	5.2% 7/135 • Number of events 15 • Throughout the study period of approximately 4 years	3.3% 4/121 • Number of events 4 • Throughout the study period of approximately 4 years
Infections and infestations Nasopharyngitis	4.7% 6/127 • Number of events 6 • Throughout the study period of approximately 4 years	7.4% 10/135 • Number of events 10 • Throughout the study period of approximately 4 years	7.4% 9/121 • Number of events 13 • Throughout the study period of approximately 4 years
Infections and infestations Upper Respiratory Tract Infection	6.3% 8/127 • Number of events 9 • Throughout the study period of approximately 4 years	5.9% 8/135 • Number of events 9 • Throughout the study period of approximately 4 years	8.3% 10/121 • Number of events 11 • Throughout the study period of approximately 4 years
Infections and infestations Urinary Tract Infection	9.4% 12/127 • Number of events 16 • Throughout the study period of approximately 4 years	5.9% 8/135 • Number of events 10 • Throughout the study period of approximately 4 years	12.4% 15/121 • Number of events 21 • Throughout the study period of approximately 4 years
Injury, poisoning and procedural complications Contusion	7.1% 9/127 • Number of events 9 • Throughout the study period of approximately 4 years	9.6% 13/135 • Number of events 17 • Throughout the study period of approximately 4 years	8.3% 10/121 • Number of events 20 • Throughout the study period of approximately 4 years
Injury, poisoning and procedural complications Fall	11.0% 14/127 • Number of events 20 • Throughout the study period of approximately 4 years	11.9% 16/135 • Number of events 20 • Throughout the study period of approximately 4 years	19.0% 23/121 • Number of events 31 • Throughout the study period of approximately 4 years
Injury, poisoning and procedural complications Laceration	5.5% 7/127 • Number of events 9 • Throughout the study period of approximately 4 years	3.7% 5/135 • Number of events 5 • Throughout the study period of approximately 4 years	7.4% 9/121 • Number of events 10 • Throughout the study period of approximately 4 years
Investigations Blood Pressure Increased	15.0% 19/127 • Number of events 65 • Throughout the study period of approximately 4 years	8.9% 12/135 • Number of events 67 • Throughout the study period of approximately 4 years	7.4% 9/121 • Number of events 49 • Throughout the study period of approximately 4 years
Investigations Weight Decreased	1.6% 2/127 • Number of events 2 • Throughout the study period of approximately 4 years	5.2% 7/135 • Number of events 8 • Throughout the study period of approximately 4 years	1.7% 2/121 • Number of events 2 • Throughout the study period of approximately 4 years
Musculoskeletal and connective tissue disorders Arthralgia	9.4% 12/127 • Number of events 12 • Throughout the study period of approximately 4 years	5.2% 7/135 • Number of events 7 • Throughout the study period of approximately 4 years	3.3% 4/121 • Number of events 4 • Throughout the study period of approximately 4 years
Musculoskeletal and connective tissue disorders Back Pain	9.4% 12/127 • Number of events 13 • Throughout the study period of approximately 4 years	8.1% 11/135 • Number of events 13 • Throughout the study period of approximately 4 years	6.6% 8/121 • Number of events 8 • Throughout the study period of approximately 4 years
Musculoskeletal and connective tissue disorders Pain In Extremity	6.3% 8/127 • Number of events 11 • Throughout the study period of approximately 4 years	3.0% 4/135 • Number of events 6 • Throughout the study period of approximately 4 years	4.1% 5/121 • Number of events 5 • Throughout the study period of approximately 4 years
Nervous system disorders Cerebral Microhaemorrhage	6.3% 8/127 • Number of events 9 • Throughout the study period of approximately 4 years	0.74% 1/135 • Number of events 1 • Throughout the study period of approximately 4 years	3.3% 4/121 • Number of events 5 • Throughout the study period of approximately 4 years
Nervous system disorders Dizziness	12.6% 16/127 • Number of events 23 • Throughout the study period of approximately 4 years	9.6% 13/135 • Number of events 16 • Throughout the study period of approximately 4 years	9.9% 12/121 • Number of events 15 • Throughout the study period of approximately 4 years
Nervous system disorders Headache	22.8% 29/127 • Number of events 114 • Throughout the study period of approximately 4 years	25.2% 34/135 • Number of events 101 • Throughout the study period of approximately 4 years	18.2% 22/121 • Number of events 65 • Throughout the study period of approximately 4 years
Nervous system disorders Tremor	0.79% 1/127 • Number of events 1 • Throughout the study period of approximately 4 years	8.9% 12/135 • Number of events 13 • Throughout the study period of approximately 4 years	4.1% 5/121 • Number of events 5 • Throughout the study period of approximately 4 years
Psychiatric disorders Agitation	7.1% 9/127 • Number of events 9 • Throughout the study period of approximately 4 years	7.4% 10/135 • Number of events 10 • Throughout the study period of approximately 4 years	8.3% 10/121 • Number of events 12 • Throughout the study period of approximately 4 years
Psychiatric disorders Anxiety	7.1% 9/127 • Number of events 12 • Throughout the study period of approximately 4 years	10.4% 14/135 • Number of events 16 • Throughout the study period of approximately 4 years	8.3% 10/121 • Number of events 15 • Throughout the study period of approximately 4 years
Psychiatric disorders Confusional State	3.9% 5/127 • Number of events 5 • Throughout the study period of approximately 4 years	9.6% 13/135 • Number of events 19 • Throughout the study period of approximately 4 years	3.3% 4/121 • Number of events 6 • Throughout the study period of approximately 4 years
Psychiatric disorders Depression	11.0% 14/127 • Number of events 14 • Throughout the study period of approximately 4 years	11.9% 16/135 • Number of events 18 • Throughout the study period of approximately 4 years	15.7% 19/121 • Number of events 22 • Throughout the study period of approximately 4 years
Psychiatric disorders Insomnia	0.79% 1/127 • Number of events 1 • Throughout the study period of approximately 4 years	6.7% 9/135 • Number of events 10 • Throughout the study period of approximately 4 years	7.4% 9/121 • Number of events 11 • Throughout the study period of approximately 4 years
Respiratory, thoracic and mediastinal disorders Cough	6.3% 8/127 • Number of events 8 • Throughout the study period of approximately 4 years	9.6% 13/135 • Number of events 19 • Throughout the study period of approximately 4 years	10.7% 13/121 • Number of events 13 • Throughout the study period of approximately 4 years
Respiratory, thoracic and mediastinal disorders Epistaxis	9.4% 12/127 • Number of events 15 • Throughout the study period of approximately 4 years	2.2% 3/135 • Number of events 3 • Throughout the study period of approximately 4 years	2.5% 3/121 • Number of events 5 • Throughout the study period of approximately 4 years
Skin and subcutaneous tissue disorders Eczema	5.5% 7/127 • Number of events 9 • Throughout the study period of approximately 4 years	2.2% 3/135 • Number of events 4 • Throughout the study period of approximately 4 years	0.83% 1/121 • Number of events 1 • Throughout the study period of approximately 4 years
Skin and subcutaneous tissue disorders Rash	16.5% 21/127 • Number of events 27 • Throughout the study period of approximately 4 years	14.1% 19/135 • Number of events 27 • Throughout the study period of approximately 4 years	5.0% 6/121 • Number of events 10 • Throughout the study period of approximately 4 years
Vascular disorders Hypertension	11.0% 14/127 • Number of events 27 • Throughout the study period of approximately 4 years	13.3% 18/135 • Number of events 27 • Throughout the study period of approximately 4 years	9.1% 11/121 • Number of events 22 • Throughout the study period of approximately 4 years
Vascular disorders Hypotension	2.4% 3/127 • Number of events 3 • Throughout the study period of approximately 4 years	4.4% 6/135 • Number of events 7 • Throughout the study period of approximately 4 years	5.8% 7/121 • Number of events 9 • Throughout the study period of approximately 4 years