Trial Outcomes & Findings for Study of the Effectiveness of Intravenous Immune Globulin (10%) for the Treatment of Multifocal Motor Neuropathy (NCT NCT00666263)

Results Overview

GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

50 participants

Primary outcome timeframe

Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Results posted on

2021-05-19

Participant Flow

Recruitment was conducted in the U.S., Canada, and Europe at 17 study sites. The first participant was enrolled in August 2008.

Fifty unique potential participants were enrolled at clinical study sites in North America and Europe. Six were screen failures. Therefore, 44 participants were randomized.

Participant milestones

Participant milestones
Measure	IGIV, 10% Then Placebo (During Cross-Over Periods) Each of the following 5 study parts is 12 weeks. Study Part 1: Open-label phase of treatment/stabilization on IGIV, 10% (Stabilization Phase 1) all participants Study Part 2: IGIV, 10% (double-blind treatment cross-over period 1) Study Part 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2) Study Part 4: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment cross-over period 2) Study Part 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3)	Placebo Then IGIV, 10% (During Cross-Over Periods) Each of the following 5 study parts is 12 weeks. Study Part 1: Open-label phase of treatment/stabilization on IGIV, 10% (Stabilization Phase 1) all participants Study Part 2: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment cross-over period 1) Study Part 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2) Study Part 4: IGIV, 10% (double-blind treatment cross-over period 2) Study Part 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3)
Study Part 1 (Stabilization Phase 1) STARTED	22	22
Study Part 1 (Stabilization Phase 1) COMPLETED	22	21
Study Part 1 (Stabilization Phase 1) NOT COMPLETED	0	1
Study Part 2 (Cross-over Period 1) STARTED	22	21
Study Part 2 (Cross-over Period 1) COMPLETED	22	21
Study Part 2 (Cross-over Period 1) NOT COMPLETED	0	0
Study Part 3 (Stabilization Phase 2) STARTED	22	21
Study Part 3 (Stabilization Phase 2) COMPLETED	22	21
Study Part 3 (Stabilization Phase 2) NOT COMPLETED	0	0
Study Part 4 (Cross-over Period 2) STARTED	22	21
Study Part 4 (Cross-over Period 2) COMPLETED	21	21
Study Part 4 (Cross-over Period 2) NOT COMPLETED	1	0
Study Part 5 (Stabilization Phase 3) STARTED	21	21
Study Part 5 (Stabilization Phase 3) COMPLETED	21	20
Study Part 5 (Stabilization Phase 3) NOT COMPLETED	0	1
End of Study Visit STARTED	22	22
End of Study Visit COMPLETED	22	22
End of Study Visit NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	IGIV, 10% Then Placebo (During Cross-Over Periods) Each of the following 5 study parts is 12 weeks. Study Part 1: Open-label phase of treatment/stabilization on IGIV, 10% (Stabilization Phase 1) all participants Study Part 2: IGIV, 10% (double-blind treatment cross-over period 1) Study Part 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2) Study Part 4: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment cross-over period 2) Study Part 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3)	Placebo Then IGIV, 10% (During Cross-Over Periods) Each of the following 5 study parts is 12 weeks. Study Part 1: Open-label phase of treatment/stabilization on IGIV, 10% (Stabilization Phase 1) all participants Study Part 2: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment cross-over period 1) Study Part 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2) Study Part 4: IGIV, 10% (double-blind treatment cross-over period 2) Study Part 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3)
Study Part 1 (Stabilization Phase 1) Adverse Event	0	1
Study Part 4 (Cross-over Period 2) Adverse Event	1	0
Study Part 5 (Stabilization Phase 3) Withdrawal by Subject	0	1

Baseline Characteristics

Study of the Effectiveness of Intravenous Immune Globulin (10%) for the Treatment of Multifocal Motor Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=44 Participants Each participant was to complete 5 study parts (3 stabilization phases of open label treatment with IGIV, 10%, and 1 cross-over period each of double-blind treatment with IGIV, 10% and placebo according to a randomized sequence). Each study part lasted 12 weeks and comprised 3, 4 or 6 infusion cycles depending on treatment interval. Study Part 1: Open-label phase of treatment/stabilization on IGIV, 10% (Stabilization Phase 1) for all participants Study Part 2: Participants were randomized to 1 of 2 sequences of double-blind treatment (either: IGIV, 10% or placebo) Study Part 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% for 12 weeks (Stabilization Phase 2) Study Part 4: Participants were crossed-over to second sequence of double-blind treatment (IGIV, 10% or placebo) Study Part 5: Participants received open-label treatment/stabilization with IGIV, 10% for 12 weeks (Stabilization Phase 3)
Age, Continuous	51.64 years STANDARD_DEVIATION 10.25 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. Each grip strength test consisted of 3 maximal repeated contractions (trials). Each participant will perform 2 sessions of grip strength testing. After a 10-minute break, the testing session will be repeated for a total of 6 grip repetitions per hand.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Grip Strength in the More Affected Hand Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	8.38 kilograms Interval 4.86 to 17.03	14.18 kilograms Interval 7.6 to 27.35	13.17 kilograms Interval 5.3 to 20.08	14.17 kilograms Interval 8.08 to 27.47	15.98 kilograms Interval 10.73 to 29.65	14.28 kilograms Interval 9.47 to 28.25	14.00 kilograms Interval 7.48 to 24.82
Grip Strength in the More Affected Hand IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	19.54 kilograms Interval 10.15 to 29.15	19.39 kilograms Interval 12.75 to 33.25	18.14 kilograms Interval 9.3 to 30.43	21.68 kilograms Interval 14.05 to 30.83	11.28 kilograms Interval 5.5 to 25.92	17.77 kilograms Interval 9.23 to 27.07	17.37 kilograms Interval 10.8 to 29.03

PRIMARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=20 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Mean Relative Change in Grip Strength in the More Affected Hand	-30.11 Percent change in grip strength Interval -48.41 to -11.81	23.86 Percent change in grip strength Interval -23.11 to 70.83	-16.36 Percent change in grip strength Interval -30.92 to -1.8	-30.52 Percent change in grip strength Interval -43.68 to -17.36	—	—	—

PRIMARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	2.0 Scores on a scale Interval 2.0 to 2.0	2.0 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 2.0	2.5 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 2.0	2.0 Scores on a scale Interval 2.0 to 2.0
Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	2.0 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 1.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 3.0	2.0 Scores on a scale Interval 2.0 to 3.0

PRIMARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=42 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=42 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=42 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS)	11.9 Proportion of participants Interval 2.0 to 3.0	47.6 Proportion of participants Interval 2.0 to 3.0	4.8 Proportion of participants Interval 2.0 to 2.0	35.7 Proportion of participants Interval 2.0 to 3.0	—	—	—

PRIMARY outcome

Timeframe: Within 72 hours of completion of an infusion during the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

The total number of all AEs which begin during or within 72 hours of completion of an infusion, irrespective of being related or not related to the study product (IGIV, 10% or Placebo), divided by the total number of infusions, and multiplied by 100.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=61 Infusions Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=138 Infusions Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=104 Infusions Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=68 Infusions Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Rate of Temporally Associated Adverse Events (AEs) Per Infusion	24.6 Percentage of AEs per infusion	11.6 Percentage of AEs per infusion	11.5 Percentage of AEs per infusion	13.2 Percentage of AEs per infusion	—	—	—

PRIMARY outcome

Timeframe: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=21 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
The Percentage of Participants for Whom the Infusion Rate of Any Infusion Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason	4.8 percentage of participants	4.8 percentage of participants	9.1 percentage of participants	0.0 percentage of participants	—	—	—

PRIMARY outcome

Timeframe: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=61 Infusions Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=138 Infusions Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=104 Infusions Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=68 Infusions Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason	1.6 percentage of infusions	0.7 percentage of infusions	2.9 percentage of infusions	0.0 percentage of infusions	—	—	—

PRIMARY outcome

Timeframe: Within 72 hours of completion of an infusion during the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=21 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
The Percentage of Participants Reporting One or More Moderate or Severe AEs That Began During Infusion or Within 72 Hours of Completion of an Infusion	19.0 percentage of participants	4.8 percentage of participants	4.5 percentage of participants	27.3 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative grip strength change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=42 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=42 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=42 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Percentage of Participants With at Least a 30% Decline in Relative Grip Strength in the More Affected Hand (Measured Using a DynEx Digital Dynamometer)	4.8 Percentage of participants	47.6 Percentage of participants	4.8 Percentage of participants	42.9 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. Each grip strength test consisted of 3 maximal repeated contractions (trials). Each participant will perform 2 sessions of grip strength testing. After a 10-minute break, the testing session will be repeated for a total of 6 grip repetitions per hand.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Grip Strength in the Less Affected Hand IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	29.79 kilograms Interval 20.48 to 37.88	29.17 kilograms Interval 21.68 to 37.7	27.98 kilograms Interval 22.35 to 36.35	29.52 kilograms Interval 23.28 to 36.98	26.58 kilograms Interval 13.67 to 32.83	28.97 kilograms Interval 15.95 to 34.38	29.68 kilograms Interval 14.72 to 34.35
Grip Strength in the Less Affected Hand Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	20.28 kilograms Interval 9.61 to 33.44	26.92 kilograms Interval 17.52 to 37.72	27.23 kilograms Interval 18.73 to 34.45	28.23 kilograms Interval 19.72 to 36.8	27.35 kilograms Interval 21.58 to 37.12	25.72 kilograms Interval 20.18 to 36.55	24.98 kilograms Interval 16.02 to 35.85

SECONDARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative Change is defined as 100 \* (End of the Cross-Over Period - Baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=20 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Mean Relative Change in Grip Strength in the Less Affected Hand	-29.22 Percent change in grip strength Interval -40.62 to -17.83	19.67 Percent change in grip strength Interval -10.84 to 50.17	-2.52 Percent change in grip strength Interval -7.9 to 2.85	-17.96 Percent change in grip strength Interval -29.81 to -6.1	—	—	—

SECONDARY outcome

Timeframe: During the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Intent to treat

Participants were permitted to switch from blinded treatment with placebo or IGIV, 10% to open label IGIV, 10% if they and investigator agreed that deterioration had occurred to the extent that the participant had unacceptable difficulty carrying out daily activities involving the affected muscles, or decline in grip strength of ≥50% in the more affected hand had occurred.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=42 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=42 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=42 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)	2.4 Proportion of participants	28.6 Proportion of participants	0.0 Proportion of participants	69.0 Proportion of participants	—	—	—

SECONDARY outcome

Timeframe: Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

Patient Global Impression of Change was measured on an ordinal scale of 1-7, higher scores representing greater perceived deterioration since the previous efficacy assessment (ranging from (1) very much improved to very much worse (7)). 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=43 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=42 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=36 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=43 Participants IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Patient Global Impression of Change IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21)	4.0 Scores on a scale Interval 4.0 to 4.0	5.0 Scores on a scale Interval 5.0 to 6.0	4.0 Scores on a scale Interval 3.0 to 4.0	4.0 Scores on a scale Interval 4.0 to 4.0	2.0 Scores on a scale Interval 2.0 to 4.0	4.0 Scores on a scale Interval 3.0 to 4.0	—
Patient Global Impression of Change Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22)	3.0 Scores on a scale Interval 2.0 to 3.0	4.0 Scores on a scale Interval 3.0 to 4.0	4.0 Scores on a scale Interval 3.0 to 4.0	6.0 Scores on a scale Interval 5.0 to 6.0	4.0 Scores on a scale Interval 4.0 to 4.0	4.0 Scores on a scale Interval 4.0 to 4.0	—

SECONDARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

The overall disability sum scale (based on Merkies et al., 2002) is a patient questionnaire that measures disability. Overall disability sum score = arm disability scale (range 0-5) + leg disability scale (range 0-7); Overall Range: 0 (no signs of disability) to 12 (maximum disability).

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Overall Disability Sum Score Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	4 Scores on a scale Interval 3.0 to 5.0	3 Scores on a scale Interval 2.0 to 4.0	3 Scores on a scale Interval 2.0 to 4.0	3 Scores on a scale Interval 2.0 to 4.0	3 Scores on a scale Interval 2.0 to 4.0	4 Scores on a scale Interval 2.0 to 4.0	3 Scores on a scale Interval 2.0 to 4.0
Overall Disability Sum Score IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	3 Scores on a scale Interval 2.0 to 4.0	2 Scores on a scale Interval 2.0 to 4.0	3 Scores on a scale Interval 2.0 to 4.0	2 Scores on a scale Interval 2.0 to 4.0	3 Scores on a scale Interval 2.0 to 4.0	2 Scores on a scale Interval 2.0 to 4.0	2 Scores on a scale Interval 2.0 to 4.0

SECONDARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

The overall disability sum scale (based on Merkies et al., 2002) is a patient questionnaire that measures disability. Overall disability sum score = arm disability scale (range 0-5) + leg disability scale (range 0-7); Overall Range: 0 (no signs of disability) to 12 (maximum disability). This was standardized to a scale of 0 to 100 (the best score being 100) to allow calculation of relative changes.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Overall Disability Sum Score - Standardized IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	79.2 Scores on a scale Interval 66.7 to 83.3	83.3 Scores on a scale Interval 66.7 to 83.3	75.0 Scores on a scale Interval 66.7 to 83.3	83.3 Scores on a scale Interval 66.7 to 83.3	75.0 Scores on a scale Interval 66.7 to 83.3	83.3 Scores on a scale Interval 66.7 to 83.3	83.3 Scores on a scale Interval 66.7 to 83.3
Overall Disability Sum Score - Standardized Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	66.7 Scores on a scale Interval 58.3 to 75.0	75.0 Scores on a scale Interval 66.7 to 83.3	75.0 Scores on a scale Interval 66.7 to 83.3	75.0 Scores on a scale Interval 66.7 to 83.3	75.0 Scores on a scale Interval 66.7 to 83.3	66.7 Scores on a scale Interval 66.7 to 83.3	75.0 Scores on a scale Interval 66.7 to 83.3

SECONDARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The overall disability sum scale (based on Merkies et al., 2002) is a patient questionnaire that measures disability (from 0, "no signs of disability" to 12, "most severe disability"). This was standardized to a scale of 0 to 100 (the best score being 100) to allow calculation of relative changes.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=20 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Mean Relative Change in Overall Disability Sum Score	-8.46 percent change in score Interval -12.81 to -4.11	0.92 percent change in score Interval -2.88 to 4.73	-3.14 percent change in score Interval -6.55 to 0.27	-5.77 percent change in score Interval -10.33 to -1.2	—	—	—

SECONDARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	20.25 Seconds Interval 18.0 to 29.0	21.00 Seconds Interval 18.0 to 24.5	20.75 Seconds Interval 19.5 to 27.5	22.00 Seconds Interval 19.5 to 29.0	20.50 Seconds Interval 18.5 to 27.5	20.50 Seconds Interval 19.0 to 24.5	20.00 Seconds Interval 19.0 to 25.5
Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	27.75 Seconds Interval 23.0 to 43.5	24.50 Seconds Interval 19.0 to 34.5	26.75 Seconds Interval 20.5 to 39.0	25.25 Seconds Interval 19.0 to 33.5	25.00 Seconds Interval 20.0 to 30.5	27.50 Seconds Interval 20.5 to 35.5	26.25 Seconds Interval 19.5 to 33.0

SECONDARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=20 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand	29.89 Percent change in time Interval 12.46 to 47.31	4.89 Percent change in time Interval -9.45 to 19.23	-2.57 Percent change in time Interval -9.99 to 4.86	3.90 Percent change in time Interval -4.59 to 12.39	—	—	—

SECONDARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their non-dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	24.00 Seconds Interval 19.5 to 28.5	23.50 Seconds Interval 19.5 to 27.0	25.75 Seconds Interval 20.0 to 29.5	22.50 Seconds Interval 19.5 to 27.0	25.25 Seconds Interval 22.5 to 29.5	21.00 Seconds Interval 19.5 to 24.5	23.00 Seconds Interval 20.5 to 26.5
Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	37.25 Seconds Interval 26.25 to 82.75	31.50 Seconds Interval 24.0 to 38.5	31.25 Seconds Interval 22.5 to 51.0	28.00 Seconds Interval 22.5 to 40.0	32.50 Seconds Interval 22.0 to 41.0	30.00 Seconds Interval 22.5 to 39.5	30.00 Seconds Interval 21.0 to 38.5

SECONDARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their non-dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=20 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand	52.93 Percent change in time Interval 26.82 to 79.05	8.56 Percent change in time Interval -4.88 to 22.01	4.78 Percent change in time Interval -1.65 to 11.21	13.06 Percent change in time Interval 4.46 to 21.65	—	—	—

SECONDARY outcome

Timeframe: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

Population: Intent to treat

The VAS measured patients' assessment of physical functioning on a 10 centimeter scale of 0-10, on which 0 represents "no symptoms" and 10 "disabled, unable to use affected limbs".

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=43 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=44 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=44 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 n=43 Participants Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 n=36 Participants IGIV, 10%	End of the Study n=43 Participants Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	7.15 Scores on a scale Interval 6.75 to 7.6	5.10 Scores on a scale Interval 2.3 to 6.1	4.95 Scores on a scale Interval 2.3 to 7.6	3.15 Scores on a scale Interval 2.7 to 5.5	4.60 Scores on a scale Interval 2.4 to 5.9	4.50 Scores on a scale Interval 2.6 to 6.0	5.15 Scores on a scale Interval 2.8 to 6.3
Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	4.10 Scores on a scale Interval 2.0 to 5.6	3.50 Scores on a scale Interval 1.7 to 5.1	4.80 Scores on a scale Interval 2.9 to 6.3	2.95 Scores on a scale Interval 1.6 to 5.1	6.85 Scores on a scale Interval 5.9 to 8.1	4.50 Scores on a scale Interval 2.6 to 5.1	3.70 Scores on a scale Interval 1.9 to 5.4

SECONDARY outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The VAS measured patients' assessment of physical functioning on a 10 centimeter scale of 0-10, on which 0 represents "no symptoms" and 10 "disabled, unable to use affected limbs".

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=20 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS)	258.09 Percent change in assessment Interval -100.83 to 617.01	5.75 Percent change in assessment Interval -11.54 to 23.04	140.92 Percent change in assessment Interval -1.35 to 283.19	321.75 Percent change in assessment Interval -73.45 to 716.95	—	—	—

SECONDARY outcome

Timeframe: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

The total number of AEs determined by the investigator to be related to the study product that occur at any time during the study divided by the total number of infusions, and multiplied by 100.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=61 Infusions Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=138 Infusions Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=104 Infusions Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=68 Infusions Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Rate of Related AEs Per Infusion	44.3 AEs per infusion	15.9 AEs per infusion	4.8 AEs per infusion	20.6 AEs per infusion	—	—	—

SECONDARY outcome

Timeframe: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

The total number of SAEs determined by the investigator to be related to the study product that occur at any time during the study divided by the total number of infusions, and multiplied by 100.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=61 Infusions Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=138 Infusions Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=104 Infusions Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=68 Infusions Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Rate of Related SAEs Per Infusion	0.0 SAEs per infusion	0.7 SAEs per infusion	0.0 SAEs per infusion	0.0 SAEs per infusion	—	—	—

SECONDARY outcome

Timeframe: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=21 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=21 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=22 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=22 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
The Proportion of Participants for Whom the Infusion Rate of Any Infusion Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs	0.0 proportion of participants	4.8 proportion of participants	0.0 proportion of participants	0.0 proportion of participants	—	—	—

SECONDARY outcome

Timeframe: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=61 Infusions Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=138 Infusions Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=104 Infusions Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=68 Infusions Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
The Proportion of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs	0.0 proportion of infusions	0.7 proportion of infusions	0.0 proportion of infusions	0.0 proportion of infusions	—	—	—

SECONDARY outcome

Timeframe: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

Population: Safety Dataset

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=61 Infusions Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=138 Infusions Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=104 Infusions Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=68 Infusions Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
The Proportion of Infusions Associated With One or More AEs Related to the Study Product	34.4 proportion of infusions	13.0 proportion of infusions	3.8 proportion of infusions	19.1 proportion of infusions	—	—	—

POST_HOC outcome

Timeframe: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Population: Intent to treat

Relative grip strength change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

Outcome measures

Outcome measures
Measure	Decline During Both Placebo and IGIV, 10% n=42 Participants Participants who experienced a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	No Decline During Placebo and IGIV, 10% n=42 Participants Participants who did not experience a relative decrease in grip strength of ≥30% in the less affected hand relative to baseline following IGIV, 10%, and the placebo	Deterioration After IGIV, 10% and Placebo n=42 Participants Participants with deterioration in GNDS scores after IGIV, 10% and placebo	Deterioration After Placebo, But Not IGIV, 10% n=42 Participants Participants with deterioration in GNDS scores after Placebo, but not IGIV, 10%	End of Cross-Over 2 Either IGIV, 10% or Placebo. The opposite of the end of Cross-Over 1.	End of Stabilization 3 IGIV, 10%	End of the Study Participants returned following last infusion cycle (2,3, or 4 weeks after last infusion during Stabilization 3) for an End-of-Study visit for assessments including; efficacy (eg: grip strength and disability assessments), adverse events collection, physical examination, laboratory and vital signs, collection and review of diaries and other assessments.
Proportion of Participants With at Least a 30% Decline in Relative Grip Strength in the Less Affected Hand (Measured Using a DynEx Digital Dynamometer)	2.4 Proportion of participants	66.7 Proportion of participants	0.0 Proportion of participants	31.0 Proportion of participants	—	—	—

Adverse Events

IGIV, 10%

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IGIV, 10% n=44 participants at risk Participants received IGIV, 10% at the same equivalent dose per week administered prior to the study (0.4 to 2.0 g per kg BW per infusion cycle)	Placebo n=43 participants at risk 0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.3% 1/44 • Number of events 1 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
Eye disorders Vision blurred	2.3% 1/44 • Number of events 1 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.

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 Baxter's 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 or 18 months after study completion. Baxter requires a review of results communications (e.g., for confidential information) ≥90 days prior to submission or communication. Baxter may request an additional delay of ≤120 days(e.g., for intellectual property protection)
Publication restrictions are in place

Restriction type: OTHER

Measure	IGIV, 10% n=44 participants at risk Participants received IGIV, 10% at the same equivalent dose per week administered prior to the study (0.4 to 2.0 g per kg BW per infusion cycle)	Placebo n=43 participants at risk 0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used)
Nervous system disorders HEADACHE	36.4% 16/44 • Number of events 34 • Throughout the study period, approximately three years.	4.7% 2/43 • Number of events 3 • Throughout the study period, approximately three years.
Nervous system disorders NEUROLOGICAL DECOMPENSATION	22.7% 10/44 • Number of events 10 • Throughout the study period, approximately three years.	58.1% 25/43 • Number of events 25 • Throughout the study period, approximately three years.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	20.5% 9/44 • Number of events 15 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	18.2% 8/44 • Number of events 12 • Throughout the study period, approximately three years.	4.7% 2/43 • Number of events 2 • Throughout the study period, approximately three years.
General disorders INFLUENZA LIKE ILLNESS	15.9% 7/44 • Number of events 9 • Throughout the study period, approximately three years.	2.3% 1/43 • Number of events 1 • Throughout the study period, approximately three years.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	15.9% 7/44 • Number of events 8 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	13.6% 6/44 • Number of events 9 • Throughout the study period, approximately three years.	4.7% 2/43 • Number of events 3 • Throughout the study period, approximately three years.
Musculoskeletal and connective tissue disorders BACK PAIN	11.4% 5/44 • Number of events 5 • Throughout the study period, approximately three years.	2.3% 1/43 • Number of events 2 • Throughout the study period, approximately three years.
Injury, poisoning and procedural complications CONTUSION	11.4% 5/44 • Number of events 9 • Throughout the study period, approximately three years.	4.7% 2/43 • Number of events 2 • Throughout the study period, approximately three years.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	9.1% 4/44 • Number of events 6 • Throughout the study period, approximately three years.	7.0% 3/43 • Number of events 3 • Throughout the study period, approximately three years.
General disorders CHEST DISCOMFORT	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
Gastrointestinal disorders DIARRHOEA	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
General disorders FATIGUE	6.8% 3/44 • Number of events 5 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
General disorders NASOPHARYNGITIS	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	4.7% 2/43 • Number of events 2 • Throughout the study period, approximately three years.
Gastrointestinal disorders NAUSEA	6.8% 3/44 • Number of events 31 • Throughout the study period, approximately three years.	4.7% 2/43 • Number of events 3 • Throughout the study period, approximately three years.
Musculoskeletal and connective tissue disorders NECK PAIN	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	2.3% 1/43 • Number of events 1 • Throughout the study period, approximately three years.
Nervous system disorders NEUROLOGICAL SYMPTOM	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	4.7% 2/43 • Number of events 2 • Throughout the study period, approximately three years.
Nervous system disorders PARAESTHESIA	6.8% 3/44 • Number of events 4 • Throughout the study period, approximately three years.	2.3% 1/43 • Number of events 1 • Throughout the study period, approximately three years.
Respiratory, thoracic and mediastinal disorders SINUS CONGESTION	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
Nervous system disorders SINUS HEADACHE	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
Gastrointestinal disorders TOOTHACHE	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.
Infections and infestations URINARY TRACT INFECTION	6.8% 3/44 • Number of events 3 • Throughout the study period, approximately three years.	0.00% 0/43 • Throughout the study period, approximately three years.