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Clinical Trial Results:
A Randomized, Double-Blind, Placebo Controlled, Cross-over Study of the Effectiveness of Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for the Treatment of Multifocal Motor Neuropathy

Summary
EudraCT number	2009-013841-27
Trial protocol	DK
Global end of trial date	11 Aug 2011

Results information
Results version number	v1(current)
This version publication date	05 Mar 2016
First version publication date	05 Mar 2016
Other versions

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

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Trial information

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Sponsor protocol code

160604

ISRCTN number

US NCT number

NCT00666263

WHO universal trial number (UTN)

Sponsor organisation name

Baxalta Innovations GmbH

Sponsor organisation address

Industriestrasse 67, Vienna, Austria, 1221

Public contact

Clinical Trial Registries and Results Disclosure, Baxalta Innovations GmbH, ClinicalTrialsDisclosure@baxalta.com

Scientific contact

Clinical Trial Registries and Results Disclosure, Baxalta Innovations GmbH, ClinicalTrialsDisclosure@baxalta.com

Sponsor organisation name

Baxalta US Inc.

Sponsor organisation address

One Baxter Way, Westlake Village, United States, CA 91362

Public contact

Clinical Trial Registries and Results Disclosure, Baxalta US Inc., ClinicalTrialsDisclosure@baxalta.com

Scientific contact

Clinical Trial Registries and Results Disclosure, Baxalta US Inc., ClinicalTrialsDisclosure@baxalta.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

11 Aug 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 Aug 2011

Was the trial ended prematurely?

Main objective of the trial

The aim of the current study was to evaluate the efficacy (effect on grip strength and disability) and safety/tolerability of Immune Globulin Intravenous (Human), 10% (IGIV, 10%) in subjects with Multifocal Motor Neuropathy (MMN).

Protection of trial subjects

This study was conducted in accordance with this protocol, the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice, Title 21 of the US Code of Federal Regulations and the European Directive.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Aug 2008

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

Denmark: 2

Country: Number of subjects enrolled

United States: 28

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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

Screening details

Fifty unique potential subjects were enrolled (signed informed consent) at clinical study sites in North America and Europe. Six were screen failures. Therefore, 44 subjects were randomized and treated.

Number of subjects started

50 ^[1]

Number of subjects completed

Reason: Number of subjects

Screen Failure: 6

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The worldwide number of subjects enrolled only included subjects treated with study product (N=44) as per definition of enrolled in EudraCT (Enrolled=Treated). The number of subjects reported in the pre-assignment period includes all subjects enrolled in the study i.e. signed informed consent (N=50).

Period 1 title

Study Part 1 (Stabilization Phase 1)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Each of the following 5 study parts was 12 weeks. 1: Open-label phase of treatment/stabilization with IGIV, 10% (Stabilization Phase 1); 2: IGIV, 10% or placebo (double-blind treatment cross-over period 1); 3: Open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2); 4: IGIV, 10% or placebo (double-blind treatment cross-over period 2); 5: Open-label phase of treatment/stabilization with IGIV, 10% (Stabilization Phase 3). Placebo was 0.25% human albumin.

Are arms mutually exclusive

Yes

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods)

Arm description

Study Part 1: Open-label phase of treatment/stabilization on Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks (Stabilization Phase 1). Includes all subjects who received IGIV, 10% during Study Part 2 (double-blind treatment cross-over Period 1) and Placebo during Study Part 4 (double-blind treatment cross-over Period 2).

Arm type

Experimental

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Immune globulin intravenous (Human), 10% (IGIV, 10%) solution consists of 1 vial of a liquid solution containing 100 mg/mL protein, of which at least 98% is Immunoglobulin (IgG). Subjects were dosed intravenously at increasing rates of infusion starting at 0.5 mL/kg body weight/hour (BM/h) and increasing to a maximum rate of 5.0 mL/kg BW/h. Alternatively Institutional Standardized Infusion Rate Protocols may be used. Rate of infusion could be adjusted at the investigator's discretion.

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Arm description

Study Part 1: Open-label phase of treatment/stabilization on Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks (Stabilization Phase 1). Includes all subjects who received Placebo during Study Part 2 (double-blind treatment cross-over Period 1) and IGIV, 10% during Study Part 4 (double-blind treatment cross-over Period 2).

Arm type

Experimental

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1	Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods)	Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)
Started	22	22
Completed	22	21
Not completed	0	1
Adverse event, non-fatal	-	1

Period 2 title

Study Part 2 (Cross-over Period 1)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Blinding implementation details

Are arms mutually exclusive

Yes

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods)

Arm description

Study Part 2: double-blind treatment cross-over period 1 for 12 weeks. Includes all subjects who received Immune Globulin Intravenous (Human), 10% (IGIV, 10%) during this study period.

Arm type

Experimental

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

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. Placebo administred at the same volume as IGIV, 10% that the subject received before being randomized.

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Arm description

Study Part 2: double-blind treatment cross-over period 1 for 12 weeks. Includes all subjects who received Placebo during this study period.

Arm type

Experimental

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 2	Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods)	Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)
Started	22	21
Completed	22	21

Period 3 title

Study Part 3 (Stabilization Phase 2)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Are arms mutually exclusive

Yes

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Arm description

Study Part 3: Stabilzation Phase 2. Between the two double-blind treatment cross-over periods, subjects received open-label treatment/stabilization with Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks. Includes all subjects who received IGIV, 10% during Study Part 2 (double-blind treatment cross-over Period 1) and Placebo during Study Part 4 (double-blind treatment cross-over Period 2).

Arm type

Experimental

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Arm description

Study Part 3: Stabilzation Phase 2. Between the two double-blind treatment cross-over periods, subjects received open-label treatment/stabilization with Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks. Includes all subjects who received Placebo during Study Part 2 (double-blind treatment cross-over Period 1) and IGIV, 10% during Study Part 4 (double-blind treatment cross-over Period 2).

Arm type

Experimental

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 3	Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods	Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)
Started	22	21
Completed	22	21

Period 4 title

Study Part 4 (Cross-over Period 2)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Are arms mutually exclusive

Yes

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Arm description

Study Part 4: double-blind treatment cross-over period 2 for 12 weeks. Includes all subjects who received Placebo during this study period.

Arm type

Experimental

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Arm description

Study Part 4: double-blind treatment cross-over period 2 for 12 weeks. Includes all subjects who received Immune Globulin Intravenous (Human), 10% (IGIV, 10%) during this study period.

Arm type

Experimental

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 4	Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods	Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)
Started	22	21
Completed	21	21
Not completed	1	0
Adverse event, non-fatal	1	-

Period 5 title

Study Part 5 (Stabilization Phase 3)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Are arms mutually exclusive

Yes

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Arm description

Study Part 5: Subjects received open-label treatment/stabilization with Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks (Stabilization Phase 3). Includes all subjects who received IGIV, 10% during Study Part 2 (double-blind treatment cross-over Period 1) and Placebo during Study Part 4 (double-blind treatment cross-over Period 2).

Arm type

Experimental

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Arm description

Study Part 5: Subjects received open-label treatment/stabilization with Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks (Stabilization Phase 3). Includes all subjects who received Placebo during Study Part 2 (double-blind treatment cross-over Period 1) and IGIV, 10% during Study Part 4 (double-blind treatment cross-over Period 2).

Arm type

Experimental

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 5	Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods	Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)
Started	21	21
Completed	21	20
Not completed	0	1
Consent withdrawn by subject	-	1

Period 6 title

End of Study Visit

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Are arms mutually exclusive

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Arm description

End of Study Visit conducted on 21 randomized subjects regardless of participation in Study Parts (except for one subject who withdrew and did not attend End of Study Visit).

Arm type

Experimental

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Arm description

End of Study Visit done on all 22 randomized subjects regardless of participation in Study Parts.

Arm type

Experimental

Investigational medicinal product name

Placebo - 0.25% Albumin (Human) Solution

Investigational medicinal product code

Other name

BUMINATE or Human Albumin 200 g/L Baxter Solution for Infusion

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

IGIV, 10%

Investigational medicinal product code

Other name

GAMMARGARD LIQUID (US, Canada), KIOVIG (EU)

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 6	Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods	Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)
Started	21	22
Completed	21	22

Baseline characteristics

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Reporting group title

Study Part 1 (Stabilization Phase 1)

Reporting group description

Study Part 1 (Stabilization Phase 1)

Reporting group values	Study Part 1 (Stabilization Phase 1)	Total
Number of subjects	44
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	51.64 ( 10.25 )	-
Gender categorical
Units: Subjects
Female	12	12
Male	32	32

End points

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Reporting group title

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods)

Reporting group description

Reporting group title

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Reporting group description

Study Part 1: Open-label phase of treatment/stabilization on Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks (Stabilization Phase 1). Includes all subjects who received Placebo during Study Part 2 (double-blind treatment cross-over Period 1) and IGIV, 10% during Study Part 4 (double-blind treatment cross-over Period 2).

Reporting group title

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods)

Reporting group description

Study Part 2: double-blind treatment cross-over period 1 for 12 weeks. Includes all subjects who received Immune Globulin Intravenous (Human), 10% (IGIV, 10%) during this study period.

Reporting group title

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Reporting group description

Study Part 2: double-blind treatment cross-over period 1 for 12 weeks. Includes all subjects who received Placebo during this study period.

Reporting group title

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Reporting group description

Reporting group title

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Reporting group description

Study Part 3: Stabilzation Phase 2. Between the two double-blind treatment cross-over periods, subjects received open-label treatment/stabilization with Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks. Includes all subjects who received Placebo during Study Part 2 (double-blind treatment cross-over Period 1) and IGIV, 10% during Study Part 4 (double-blind treatment cross-over Period 2).

Reporting group title

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Reporting group description

Study Part 4: double-blind treatment cross-over period 2 for 12 weeks. Includes all subjects who received Placebo during this study period.

Reporting group title

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Reporting group description

Study Part 4: double-blind treatment cross-over period 2 for 12 weeks. Includes all subjects who received Immune Globulin Intravenous (Human), 10% (IGIV, 10%) during this study period.

Reporting group title

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Reporting group description

Reporting group title

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Reporting group description

Study Part 5: Subjects received open-label treatment/stabilization with Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for 12 weeks (Stabilization Phase 3). Includes all subjects who received Placebo during Study Part 2 (double-blind treatment cross-over Period 1) and IGIV, 10% during Study Part 4 (double-blind treatment cross-over Period 2).

Reporting group title

Arm 1: IGIV, 10% then Placebo (During Cross-Over Periods

Reporting group description

End of Study Visit conducted on 21 randomized subjects regardless of participation in Study Parts (except for one subject who withdrew and did not attend End of Study Visit).

Reporting group title

Arm 2: Placebo then IGIV, 10% (During Cross-Over Periods)

Reporting group description

End of Study Visit done on all 22 randomized subjects regardless of participation in Study Parts.

Subject analysis set title

Before Stabilization 1 - All Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Baseline Measurements

Subject analysis set title

End of Stabilization 1 - All Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Immune Globulin Intravenous (Human), 10% (IGIV, 10%)

Subject analysis set title

End of Cross-Over 1 - All Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Either Immune Globulin Intravenous (Human), 10% (IGIV, 10%) or Placebo

Subject analysis set title

End of Stabilization 2 - All Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Immune Globulin Intravenous (Human), 10% (IGIV, 10%)

Subject analysis set title

End of Cross-Over 2 - All Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Either Immune Globulin Intravenous (Human), 10% (IGIV, 10%) or Placebo. The opposite of the end of Cross-Over 1.

Subject analysis set title

End of Stabilization 3 - All Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Immune Globulin Intravenous (Human), 10% (IGIV, 10%)

Subject analysis set title

End of Study - All Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects 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.

Subject analysis set title

Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Cross-over Period 1

Subject analysis set type

Sub-group analysis

Subject analysis set description

Study Part 1: Open-label phase of treatment/stabilization on Immune Globulin Intravenous (Human), 10% (IGIV, 10%) (Stabilization Phase 1) all subjects; Study Part 2: IGIV, 10% (double-blind treatment cross-over Period 1); Study Part 3: Between the two double-blind treatment cross-over periods, subjects received open-label treatment/stabilization with IGIV, 10% for 12 weeks (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: Subjects received open-label treatment/stabilization with IGIV, 10% for 12 weeks (Stabilization Phase 3).

Subject analysis set title

Arm 1: IGIV, 10% Then Placebo- Placebo Cross-over Period 2

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm 2: Placebo Then IGIV, 10% - Placebo Cross-over Period 1

Subject analysis set type

Sub-group analysis

Subject analysis set description

Study Part 1: Open-label phase of treatment/stabilization on Immune Globulin Intravenous (Human), 10% (IGIV, 10%) (Stabilization Phase 1) all subjects; 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, subjects received open-label treatment/stabilization with IGIV, 10% for 12 weeks (Stabilization Phase 2); Study Part 4: IGIV, 10% (double-blind treatment cross-over Period 2); Study Part 5: Subjects received open-label treatment/stabilization with IGIV, 10% for 12 weeks (Stabilization Phase 3).

Subject analysis set title

Arm 2: Placebo Then IGIV, 10% - IGIV, 10% Cross-over Period 2

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Deterioration After IGIV, 10% and Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects with deterioration in Guy's Neurological Disability Scale (GNDS) scores after Immune Globulin Intravenous (Human), 10% (IGIV, 10%) and Placebo.

Subject analysis set title

Deterioration After Placebo, But Not IGIV, 10%

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects with deterioration in Guy's Neurological Disability Scale (GNDS) scores after Placebo, but not Immune Globulin Intravenous (Human), 10% (IGIV, 10%) .

Subject analysis set title

Deterioration After IGIV, 10%, But Not Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects with deterioration in Guy's Neurological Disability Scale (GNDS) scores after Immune Globulin Intravenous (Human), 10% (IGIV, 10%), but not Placebo.

Subject analysis set title

No Deterioration After IGIV, 10% or Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects with no deterioration in Guy's Neurological Disability Scale (GNDS) scores after Immune Globulin Intravenous (Human), 10% (IGIV, 10%) or Placebo.

Subject analysis set title

Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Arm 1: IGIV, 10% Then Placebo- Placebo Period

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Arm 2: Placebo Then IGIV, 10%- Placebo Period

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Decline Only During IGIV, 10%

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who experienced a relative decrease in grip strength of ≥30% in the more affected hand relative to baseline following Immune Globulin Intravenous (Human), 10% (IGIV, 10%), but not after Placebo.

Subject analysis set title

Decline Only During Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who experienced a relative decrease in grip strength of ≥30% in the more affected hand relative to baseline following the placebo, but not after Immune Globulin Intravenous (Human), 10% (IGIV, 10%).

Subject analysis set title

Decline During Both Placebo and IGIV, 10%

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who experienced a relative decrease in grip strength of ≥30% in the more affected hand relative to baseline following Immune Globulin Intravenous (Human), 10% (IGIV, 10%) %, and Placebo.

Subject analysis set title

No Decline During Placebo and IGIV, 10%

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who did not experience a relative decrease in grip strength of ≥30% in the more affected hand relative to baseline following Immune Globulin Intravenous (Human), 10% (IGIV, 10%), and Placebo.

Subject analysis set title

Accelerated Switch During IGIV, 10% and Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who required a switch to open label IGIV, 10% when receiving Immune Globulin Intravenous (Human), 10% (IGIV, 10%), and Placebo.

Subject analysis set title

Accelerated Switch During Placebo, But Not IGIV, 10%

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who required a switch to open label Immune Globulin Intravenous (Human), 10% (IGIV, 10%) when receiving Placebo, but not during IGIV, 10%.

Subject analysis set title

Accelerated Switch During IGIV, 10%, But Not Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who required a switch to open label Immune Globulin Intravenous (Human), 10% (IGIV, 10%) when receiving IGIV, 10%, but not during Placebo.

Subject analysis set title

No Accelerated Switch During IGIV, 10% or Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who did not require a switch to open label Immune Globulin Intravenous (Human), 10% (IGIV, 10%) when receiving IGIV, 10%, or Placebo.

Primary: Grip Strength in the More Affected Hand

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End point title

Grip Strength in the More Affected Hand ^[1]

End point description

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 subject 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. Population: Intent To Treat.

End point type

Primary

End point 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

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics were collected for this endpoint.

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: kilograms
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	18.14 (9.3 to 30.43)	21.68 (14.05 to 30.83)	19.54 (10.15 to 29.15)	19.39 (12.75 to 33.25)	11.28 (5.5 to 25.92)	17.77 (9.23 to 27.07)	17.37 (10.8 to 29.03)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	13.17 (5.3 to 20.08)	14.17 (8.08 to 27.47)	8.38 (4.86 to 17.03)	14.18 (7.6 to 27.35)	15.98 (10.73 to 29.65)	14.28 (9.47 to 28.25)	14 (7.48 to 24.82)

No statistical analyses for this end point

Primary: Mean Relative Change in Grip Strength in the More Affected Hand

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End point title

Mean Relative Change in Grip Strength in the More Affected Hand ^[2]

End point description

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. Population: Intent To Treat.

End point type

Primary

End point 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)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Currently unable to enter statistical analysis due to limitation of EudraCT. Statistics are available for these study results in ClinicalTrials.gov (NCT00666263).

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Cross-over Period 1	Arm 1: IGIV, 10% Then Placebo- Placebo Cross-over Period 2	Arm 2: Placebo Then IGIV, 10% - Placebo Cross-over Period 1	Arm 2: Placebo Then IGIV, 10% - IGIV, 10% Cross-over Period 2
Number of subjects analysed	22	22	20	21
Units: Percent change in grip strength
arithmetic mean (confidence interval 95%)	-16.36 (-30.92 to -1.8)	-30.52 (-43.68 to -17.36)	-30.11 (-48.41 to -11.81)	23.86 (-23.11 to 70.83)

No statistical analyses for this end point

Primary: Co-Primary Endpoint: Guy's Neurological Disability Score (GNDS) for Upper Limbs

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End point title

Co-Primary Endpoint: Guy's Neurological Disability Score (GNDS) for Upper Limbs ^[3]

End point description

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

End point type

Primary

End point 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

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics were collected for this endpoint.

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: Scores on a scale
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	2 (2 to 3)	2 (2 to 2)	2 (2 to 2)	2 (2 to 3)	2.5 (2 to 3)	2 (2 to 2)	2 (2 to 2)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	2 (2 to 3)	2 (2 to 3)	2 (2 to 3)	2 (1 to 3)	2 (2 to 3)	2 (2 to 3)	2 (2 to 3)

No statistical analyses for this end point

Primary: Co-Primary Endpoint: Proportion of Subjects with Deterioration in Guy’s Neurological Disability Score (GNDS)

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End point title

Co-Primary Endpoint: Proportion of Subjects with Deterioration in Guy’s Neurological Disability Score (GNDS) ^[4]

End point description

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

End point type

Primary

End point 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)

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Currently unable to enter statistical analysis due to limitation of EudraCT. Statistics are available for these study results in ClinicalTrials.gov (NCT00666263).

End point values	Deterioration After IGIV, 10% and Placebo	Deterioration After Placebo, But Not IGIV, 10%	Deterioration After IGIV, 10%, But Not Placebo	No Deterioration After IGIV, 10% or Placebo
Number of subjects analysed	42	42	42	42
Units: Proportion of subjects
number (not applicable)	4.8	35.7	11.9	47.6

No statistical analyses for this end point

Primary: Rate of temporally associated adverse events (AEs) per infusion

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End point title

Rate of temporally associated adverse events (AEs) per infusion ^[5]

End point description

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. Population: Safety Dataset. Number of infusions [N] analyzed per subject analysis set is as follows: Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period N=104; Arm 1: IGIV, 10% Then Placebo- Placebo Period N=68; Arm 2: Placebo Then IGIV, 10%- Placebo Period N=61; Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period N=138.

End point type

Primary

End point 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)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics were collected for this endpoint.

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: Percentage of AEs per infusion
number (not applicable)	11.5	13.2	24.6	11.6

No statistical analyses for this end point

Primary: The percentage of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for any reason

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End point title

The percentage of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for any reason ^[6]

End point description

Population: Safety Dataset.

End point type

Primary

End point timeframe

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

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics were collected for this endpoint.

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: percentage of subjects
number (not applicable)	9.1	0	4.8	4.8

No statistical analyses for this end point

Primary: The percentage of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for any reason

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End point title

The percentage of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for any reason ^[7]

End point description

Number of infusions [N] analyzed per subject analysis set is as follows: Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period N=104; Arm 1: IGIV, 10% Then Placebo- Placebo Period N=68; Arm 2: Placebo Then IGIV, 10%- Placebo Period N=61; Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period N=138. Population: Safety Dataset.

End point type

Primary

End point timeframe

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

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics were collected for this endpoint.

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: percentage of infusions
number (not applicable)	2.9	0	1.6	0.7

No statistical analyses for this end point

Primary: The percentage of subjects reporting one or more moderate or severe AEs that began during infusion or within 72 hours of completion of an infusion

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End point title

The percentage of subjects reporting one or more moderate or severe AEs that began during infusion or within 72 hours of completion of an infusion ^[8]

End point description

Population: Safety Dataset.

End point type

Primary

End point 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)

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics were collected for this endpoint.

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: percentage of subjects
number (not applicable)	4.5	27.3	19	4.8

No statistical analyses for this end point

Secondary: Percentage of subjects with at least a 30% decline in relative grip strength in the more affected hand (measured using a DynEx digital dynamometer)

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End point title

Percentage of subjects with at least a 30% decline in relative grip strength in the more affected hand (measured using a DynEx digital dynamometer)

End point description

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. Population: Intent to Treat.

End point type

Secondary

End point 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)

End point values	Decline Only During IGIV, 10%	Decline Only During Placebo	Decline During Both Placebo and IGIV, 10%	No Decline During Placebo and IGIV, 10%
Number of subjects analysed	42	42	42	42
Units: Percentage of subjects
number (not applicable)	4.8	42.9	4.8	47.6

No statistical analyses for this end point

Secondary: Grip Strength in the Less Affected Hand

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End point title

Grip Strength in the Less Affected Hand

End point description

End point type

Secondary

End point 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

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: kilograms
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	27.98 (22.35 to 36.35)	29.52 (23.28 to 36.98)	29.79 (20.48 to 37.88)	29.17 (21.68 to 37.7)	26.58 (13.67 to 32.83)	28.97 (15.95 to 34.38)	29.68 (14.72 to 34.35)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	27.23 (18.73 to 34.45)	28.23 (19.72 to 36.8)	20.28 (9.61 to 33.44)	26.92 (17.52 to 37.72)	27.35 (21.58 to 37.12)	25.72 (20.18 to 36.55)	24.98 (16.02 to 35.85)

No statistical analyses for this end point

Secondary: Mean Relative Change in Grip Strength in the Less Affected Hand

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End point title

Mean Relative Change in Grip Strength in the Less Affected Hand

End point description

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. Population: Intent to Treat.

End point type

Secondary

End point 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)

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Cross-over Period 1	Arm 1: IGIV, 10% Then Placebo- Placebo Cross-over Period 2	Arm 2: Placebo Then IGIV, 10% - Placebo Cross-over Period 1	Arm 2: Placebo Then IGIV, 10% - IGIV, 10% Cross-over Period 2
Number of subjects analysed	22	22	20	21
Units: Percent change in grip strength
arithmetic mean (confidence interval 95%)	-2.52 (-7.9 to 2.85)	-17.96 (-29.81 to -6.1)	-29.22 (-40.62 to -17.83)	19.67 (-10.84 to 50.17)

No statistical analyses for this end point

Secondary: Proportion of Subjects That Were Accelerated Forward into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)

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End point title

Proportion of Subjects That Were Accelerated Forward into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)

End point description

Subjects 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 subject 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. Population: Intent to Treat.

End point type

Secondary

End point timeframe

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

End point values	Accelerated Switch During IGIV, 10% and Placebo	Accelerated Switch During Placebo, But Not IGIV, 10%	Accelerated Switch During IGIV, 10%, But Not Placebo	No Accelerated Switch During IGIV, 10% or Placebo
Number of subjects analysed	42	42	42	42
Units: Proportion of subjects
number (not applicable)	0	69	2.4	28.6

No statistical analyses for this end point

Secondary: Patient Global Impression of Change

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End point title

Patient Global Impression of Change

End point description

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. Population: Intent to Treat.

End point type

Secondary

End point 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

End point values	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	42	43	43	36	43
Units: Scores on a scale
median (inter-quartile range (Q1-Q3))
IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21)	4 (3 to 4)	4 (4 to 4)	4 (4 to 4)	5 (5 to 6)	2 (2 to 4)	4 (3 to 4)
Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22)	4 (3 to 4)	6 (5 to 6)	3 (2 to 3)	4 (3 to 4)	4 (4 to 4)	4 (4 to 4)

No statistical analyses for this end point

Secondary: Overall Disability Sum Score

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End point title

Overall Disability Sum Score

End point description

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). Population: Intent to Treat.

End point type

Secondary

End point 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

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: Scores on a scale
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	3 (2 to 4)	2 (2 to 4)	3 (2 to 4)	2 (2 to 4)	3 (2 to 4)	2 (2 to 4)	2 (2 to 4)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	3 (2 to 4)	3 (2 to 4)	4 (3 to 5)	3 (2 to 4)	3 (2 to 4)	4 (2 to 4)	3 (2 to 4)

No statistical analyses for this end point

Secondary: Overall Disability Sum Score - Standardized

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End point title

Overall Disability Sum Score - Standardized

End point description

End point type

Secondary

End point 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

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: Scores on a scale
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	75 (66.7 to 83.3)	83.3 (66.7 to 83.3)	79.2 (66.7 to 83.3)	83.3 (66.7 to 83.3)	75 (66.7 to 83.3)	83.3 (66.7 to 83.3)	83.3 (66.7 to 83.3)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	75 (66.7 to 83.3)	75 (66.7 to 83.3)	66.7 (58.3 to 75)	75 (66.7 to 83.3)	75 (66.7 to 83.3)	66.7 (66.7 to 83.3)	75 (66.7 to 83.3)

No statistical analyses for this end point

Secondary: Mean Relative Change in Overall Disability Sum Score

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End point title

Mean Relative Change in Overall Disability Sum Score

End point description

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. Population: Intent to Treat.

End point type

Secondary

End point 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)

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Cross-over Period 1	Arm 1: IGIV, 10% Then Placebo- Placebo Cross-over Period 2	Arm 2: Placebo Then IGIV, 10% - Placebo Cross-over Period 1	Arm 2: Placebo Then IGIV, 10% - IGIV, 10% Cross-over Period 2
Number of subjects analysed	22	22	20	21
Units: Percent change in score
arithmetic mean (confidence interval 95%)	-3.14 (-6.55 to 0.27)	-5.77 (-10.33 to -1.2)	-8.46 (-12.81 to -4.11)	0.92 (-2.88 to 4.73)

No statistical analyses for this end point

Secondary: Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Dominant Hand

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End point title

Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Dominant Hand

End point description

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Subjects 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, subjects removed the pegs one at a time and returned them to the container as quickly as possible. Each subject did this two times with their dominant hand. The 9-HCT objective is to see how fast subjects could put all of the pegs in and take them out again. Population: Intent to Treat.

End point type

Secondary

End point 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

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: Seconds
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	20.75 (19.5 to 27.5)	22 (19.5 to 29)	20.25 (18 to 29)	21 (18 to 24.5)	20.5 (18.5 to 27.5)	20.5 (19 to 24.5)	20 (19 to 25.5)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	26.75 (20.5 to 39)	25.25 (19 to 33.5)	27.75 (23 to 43.5)	24.5 (19 to 34.5)	25 (20 to 30.5)	27.5 (20.5 to 35.5)	26.25 (19.5 to 33)

No statistical analyses for this end point

Secondary: Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand

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End point title

Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand

End point description

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. Subjects 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, subjects removed the pegs one at a time and returned them to the container as quickly as possible. Each subject did this two times with their dominant hand. The 9-HCT objective is to see how fast subjects could put all of the pegs in and take them out again. Population: Intent to Treat.

End point type

Secondary

End point 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)

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Cross-over Period 1	Arm 1: IGIV, 10% Then Placebo- Placebo Cross-over Period 2	Arm 2: Placebo Then IGIV, 10% - Placebo Cross-over Period 1	Arm 2: Placebo Then IGIV, 10% - IGIV, 10% Cross-over Period 2
Number of subjects analysed	22	22	20	21
Units: Percent change in time
arithmetic mean (confidence interval 95%)	-2.57 (-9.99 to 4.86)	3.9 (-4.59 to 12.39)	29.89 (12.46 to 47.31)	4.89 (-9.45 to 19.23)

No statistical analyses for this end point

Secondary: Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Non-Dominant Hand

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End point title

Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Non-Dominant Hand

End point description

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Subjects 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, subjects removed the pegs one at a time and returned them to the container as quickly as possible. Each subject did this two times with their non-dominant hand. The 9-HCT objective is to see how fast subjects could put all of the pegs in and take them out again. Population: Intent to Treat.

End point type

Secondary

End point 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

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: Seconds
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	25.75 (20 to 29.5)	22.5 (19.5 to 27)	24 (19.5 to 28.5)	23.5 (19.5 to 27)	25.25 (22.5 to 29.5)	21 (19.5 to 24.5)	23 (20.5 to 26.5)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	31.25 (22.5 to 51)	28 (22.5 to 40)	37.25 (26.25 to 82.75)	31.5 (24 to 38.5)	32.5 (22 to 41)	30 (22.5 to 39.5)	30 (21 to 38.5)

No statistical analyses for this end point

Secondary: Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand

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End point title

Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand

End point description

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. Subjects 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, subjects removed the pegs one at a time and returned them to the container as quickly as possible. Each subject did this two times with their non-dominant hand. The 9-HCT objective is to see how fast subjects could put all of the pegs in and take them out again. Population: Intent to Treat.

End point type

Secondary

End point 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)

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Cross-over Period 1	Arm 1: IGIV, 10% Then Placebo- Placebo Cross-over Period 2	Arm 2: Placebo Then IGIV, 10% - Placebo Cross-over Period 1	Arm 2: Placebo Then IGIV, 10% - IGIV, 10% Cross-over Period 2
Number of subjects analysed	22	22	20	21
Units: Percent change in time
arithmetic mean (confidence interval 95%)	4.78 (-1.65 to 11.21)	13.06 (4.46 to 21.65)	52.93 (26.82 to 79.05)	8.56 (-4.88 to 22.01)

No statistical analyses for this end point

Secondary: Subjects' Assessment of physical functioning on a Visual Analog Scale (VAS)

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End point title

Subjects' Assessment of physical functioning on a Visual Analog Scale (VAS)

End point description

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”. Population: Intent to Treat.

End point type

Secondary

End point 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

End point values	Before Stabilization 1 - All Subjects	End of Stabilization 1 - All Subjects	End of Cross-Over 1 - All Subjects	End of Stabilization 2 - All Subjects	End of Cross-Over 2 - All Subjects	End of Stabilization 3 - All Subjects	End of Study - All Subjects
Number of subjects analysed	44	44	42	43	43	36	43
Units: Scores on a scale
median (inter-quartile range (Q1-Q3))
IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21)	4.8 (2.9 to 6.3)	2.95 (1.6 to 5.1)	4.1 (2 to 5.6)	3.5 (1.7 to 5.1)	6.85 (5.9 to 8.1)	4.5 (2.6 to 5.1)	3.7 (1.9 to 5.4)
Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22)	4.95 (2.3 to 7.6)	3.15 (2.7 to 5.5)	7.15 (6.75 to 7.6)	5.1 (2.3 to 6.1)	4.6 (2.4 to 5.9)	4.5 (2.6 to 6)	5.15 (2.8 to 6.3)

No statistical analyses for this end point

Secondary: Mean Relative Change in Subjects' Assessment of Physical Functioning on a Visual Analog Scale (VAS)

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End point title

Mean Relative Change in Subjects' Assessment of Physical Functioning on a Visual Analog Scale (VAS)

End point description

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”. Population: Intent to Treat.

End point type

Secondary

End point 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)

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Cross-over Period 1	Arm 1: IGIV, 10% Then Placebo- Placebo Cross-over Period 2	Arm 2: Placebo Then IGIV, 10% - Placebo Cross-over Period 1	Arm 2: Placebo Then IGIV, 10% - IGIV, 10% Cross-over Period 2
Number of subjects analysed	22	22	20	21
Units: Percent change in assessment
arithmetic mean (confidence interval 95%)	140.92 (-1.35 to 283.19)	321.75 (-73.45 to 716.95)	258.09 (-100.83 to 617.01)	5.75 (-11.54 to 23.04)

No statistical analyses for this end point

Secondary: Rate of related AEs per infusion

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End point title

Rate of related AEs per infusion

End point description

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. Number of infusions [N] analyzed per subject analysis set is as follows: Arm 1 - 10% Period N=104; Arm 1 - Placebo Period N=68; Arm 2 - 10% Period; Arm 2 - Placebo Period N=61; Arm 2 - 10% Period N=138. Population: Safety Dataset.

End point type

Secondary

End point timeframe

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

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: AEs per infusion
number (not applicable)	4.8	20.6	44.3	15.9

No statistical analyses for this end point

Secondary: Rate of related SAEs per infusion

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End point title

Rate of related SAEs per infusion

End point description

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. Number of infusions [N] analyzed per subject analysis set is as follows: Arm 1 - 10% Period N=104; Arm 1 - Placebo Period N=68; Arm 2 - 10% Period; Arm 2 - Placebo Period N=61; Arm 2 - 10% Period N=138. Population: Safety Dataset.

End point type

Secondary

End point timeframe

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

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: SAEs per infusion
number (not applicable)	0	0	0	0.7

No statistical analyses for this end point

Secondary: The proportion of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

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End point title

The proportion of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

End point description

Population: Safety Dataset.

End point type

Secondary

End point timeframe

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

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: Proportion of subjects
number (not applicable)	0	0	0	4.8

No statistical analyses for this end point

Secondary: The proportion of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

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End point title

The proportion of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

End point description

Number of infusions [N] analyzed per subject analysis set is as follows: Arm 1 - 10% Period N=104; Arm 1 - Placebo Period N=68; Arm 2 - 10% Period; Arm 2 - Placebo Period N=61; Arm 2 - 10% Period N=138. Population: Safety Dataset.

End point type

Secondary

End point timeframe

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

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: proportion of infusions
number (not applicable)	0	0	0	0.7

No statistical analyses for this end point

Secondary: The proportion of infusions associated with one or more AEs related to the study product

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End point title

The proportion of infusions associated with one or more AEs related to the study product

End point description

End point type

Secondary

End point timeframe

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

End point values	Arm 1: IGIV, 10% Then Placebo- IGIV, 10% Period	Arm 1: IGIV, 10% Then Placebo- Placebo Period	Arm 2: Placebo Then IGIV, 10%- Placebo Period	Arm 2: Placebo Then IGIV, 10%- IGIV, 10% Period
Number of subjects analysed	22	22	21	21
Units: proportion of infusions
number (not applicable)	3.8	19.1	34.4	13

No statistical analyses for this end point

Post-hoc: Proportion of subjects with at least a 30% decline in relative grip strength in the less affected hand (measured using a DynEx digital dynamometer)

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End point title

Proportion of subjects with at least a 30% decline in relative grip strength in the less affected hand (measured using a DynEx digital dynamometer)

End point description

End point type

Post-hoc

End point 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)

End point values	Decline Only During IGIV, 10%	Decline Only During Placebo	Decline During Both Placebo and IGIV, 10%	No Decline During Placebo and IGIV, 10%
Number of subjects analysed	42	42	42	42
Units: Proportion of subjects
number (not applicable)	0	31	2.4	66.7

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Throughout the study period, approximately three years.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Not known

Reporting group title

IGIV, 10%

Reporting group description

Subjects 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)

Reporting group title

Placebo

Reporting group description

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)

Serious adverse events	IGIV, 10%	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 44 (4.55%)	0 / 43 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Eye disorders
Vision blurred
subjects affected / exposed	1 / 44 (2.27%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	1 / 44 (2.27%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	IGIV, 10%	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	35 / 44 (79.55%)	33 / 43 (76.74%)
Injury, poisoning and procedural complications
CONTUSION
subjects affected / exposed	5 / 44 (11.36%)	2 / 43 (4.65%)
occurrences all number	9	2
Nervous system disorders
HEADACHE
subjects affected / exposed	16 / 44 (36.36%)	2 / 43 (4.65%)
occurrences all number	34	3
NEUROLOGICAL DECOMPENSATION
subjects affected / exposed	10 / 44 (22.73%)	25 / 43 (58.14%)
occurrences all number	10	25
NEUROLOGICAL SYMPTOM
subjects affected / exposed	3 / 44 (6.82%)	2 / 43 (4.65%)
occurrences all number	3	2
PARAESTHESIA
subjects affected / exposed	3 / 44 (6.82%)	1 / 43 (2.33%)
occurrences all number	4	1
SINUS HEADACHE
subjects affected / exposed	3 / 44 (6.82%)	0 / 43 (0.00%)
occurrences all number	3	0
General disorders and administration site conditions
INFLUENZA LIKE ILLNESS
subjects affected / exposed	7 / 44 (15.91%)	1 / 43 (2.33%)
occurrences all number	9	1
CHEST DISCOMFORT
subjects affected / exposed	3 / 44 (6.82%)	0 / 43 (0.00%)
occurrences all number	3	0
FATIGUE
subjects affected / exposed	3 / 44 (6.82%)	0 / 43 (0.00%)
occurrences all number	5	0
NASOPHARYNGITIS
subjects affected / exposed	3 / 44 (6.82%)	2 / 43 (4.65%)
occurrences all number	3	2
Gastrointestinal disorders
DIARRHOEA
subjects affected / exposed	3 / 44 (6.82%)	0 / 43 (0.00%)
occurrences all number	3	0
NAUSEA
subjects affected / exposed	3 / 44 (6.82%)	2 / 43 (4.65%)
occurrences all number	31	3
TOOTHACHE
subjects affected / exposed	3 / 44 (6.82%)	0 / 43 (0.00%)
occurrences all number	3	0
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
subjects affected / exposed	7 / 44 (15.91%)	0 / 43 (0.00%)
occurrences all number	8	0
SINUS CONGESTION
subjects affected / exposed	3 / 44 (6.82%)	0 / 43 (0.00%)
occurrences all number	3	0
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
subjects affected / exposed	8 / 44 (18.18%)	2 / 43 (4.65%)
occurrences all number	12	2
MUSCULAR WEAKNESS
subjects affected / exposed	6 / 44 (13.64%)	2 / 43 (4.65%)
occurrences all number	9	3
BACK PAIN
subjects affected / exposed	5 / 44 (11.36%)	1 / 43 (2.33%)
occurrences all number	5	2
PAIN IN EXTREMITY
subjects affected / exposed	4 / 44 (9.09%)	3 / 43 (6.98%)
occurrences all number	6	3
NECK PAIN
subjects affected / exposed	3 / 44 (6.82%)	1 / 43 (2.33%)
occurrences all number	3	1
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	9 / 44 (20.45%)	0 / 43 (0.00%)
occurrences all number	15	0
URINARY TRACT INFECTION
subjects affected / exposed	3 / 44 (6.82%)	0 / 43 (0.00%)
occurrences all number	3	0

More information

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Were there any global substantial amendments to the protocol? Yes

05 Dec 2008

Changes in inclusion and exclusion criteria.

05 Jan 2010

Rescue option for subjects who do not return to baseline after an accelerated switch described, changes in exclusion criteria, Data Monitoring Committee added, details of blinding/unblinded product added.

01 Mar 2011

Changes in inclusion criteria.

Were there any global interruptions to the trial? No

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

None reported

http://www.ncbi.nlm.nih.gov/pubmed/11971045
http://www.ncbi.nlm.nih.gov/pubmed/10467380

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Clinical trials

Clinical Trial Results: A Randomized, Double-Blind, Placebo Controlled, Cross-over Study of the Effectiveness of Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for the Treatment of Multifocal Motor Neuropathy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Grip Strength in the More Affected Hand

Primary: Grip Strength in the More Affected Hand

Primary: Mean Relative Change in Grip Strength in the More Affected Hand

Primary: Mean Relative Change in Grip Strength in the More Affected Hand

Primary: Co-Primary Endpoint: Guy's Neurological Disability Score (GNDS) for Upper Limbs

Primary: Co-Primary Endpoint: Guy's Neurological Disability Score (GNDS) for Upper Limbs

Primary: Co-Primary Endpoint: Proportion of Subjects with Deterioration in Guy’s Neurological Disability Score (GNDS)

Primary: Co-Primary Endpoint: Proportion of Subjects with Deterioration in Guy’s Neurological Disability Score (GNDS)

Primary: Rate of temporally associated adverse events (AEs) per infusion

Primary: Rate of temporally associated adverse events (AEs) per infusion

Primary: The percentage of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for any reason

Primary: The percentage of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for any reason

Primary: The percentage of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for any reason

Primary: The percentage of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for any reason

Primary: The percentage of subjects reporting one or more moderate or severe AEs that began during infusion or within 72 hours of completion of an infusion

Primary: The percentage of subjects reporting one or more moderate or severe AEs that began during infusion or within 72 hours of completion of an infusion

Secondary: Percentage of subjects with at least a 30% decline in relative grip strength in the more affected hand (measured using a DynEx digital dynamometer)

Secondary: Percentage of subjects with at least a 30% decline in relative grip strength in the more affected hand (measured using a DynEx digital dynamometer)

Secondary: Grip Strength in the Less Affected Hand

Secondary: Grip Strength in the Less Affected Hand

Secondary: Mean Relative Change in Grip Strength in the Less Affected Hand

Secondary: Mean Relative Change in Grip Strength in the Less Affected Hand

Secondary: Proportion of Subjects That Were Accelerated Forward into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)

Secondary: Proportion of Subjects That Were Accelerated Forward into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)

Secondary: Patient Global Impression of Change

Secondary: Patient Global Impression of Change

Secondary: Overall Disability Sum Score

Secondary: Overall Disability Sum Score

Secondary: Overall Disability Sum Score - Standardized

Secondary: Overall Disability Sum Score - Standardized

Secondary: Mean Relative Change in Overall Disability Sum Score

Secondary: Mean Relative Change in Overall Disability Sum Score

Secondary: Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Dominant Hand

Secondary: Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Dominant Hand

Secondary: Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand

Secondary: Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand

Secondary: Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Non-Dominant Hand

Secondary: Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) with the Non-Dominant Hand

Secondary: Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand

Secondary: Mean Relative Change in Time Required by Subjects to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand

Secondary: Subjects' Assessment of physical functioning on a Visual Analog Scale (VAS)

Secondary: Subjects' Assessment of physical functioning on a Visual Analog Scale (VAS)

Secondary: Mean Relative Change in Subjects' Assessment of Physical Functioning on a Visual Analog Scale (VAS)

Secondary: Mean Relative Change in Subjects' Assessment of Physical Functioning on a Visual Analog Scale (VAS)

Secondary: Rate of related AEs per infusion

Secondary: Rate of related AEs per infusion

Secondary: Rate of related SAEs per infusion

Secondary: Rate of related SAEs per infusion

Secondary: The proportion of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

Secondary: The proportion of subjects for whom the infusion rate of any infusion was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

Secondary: The proportion of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

Secondary: The proportion of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped for tolerability concerns/AEs

Secondary: The proportion of infusions associated with one or more AEs related to the study product

Secondary: The proportion of infusions associated with one or more AEs related to the study product

Post-hoc: Proportion of subjects with at least a 30% decline in relative grip strength in the less affected hand (measured using a DynEx digital dynamometer)

Post-hoc: Proportion of subjects with at least a 30% decline in relative grip strength in the less affected hand (measured using a DynEx digital dynamometer)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
A Randomized, Double-Blind, Placebo Controlled, Cross-over Study of the Effectiveness of Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for the Treatment of Multifocal Motor Neuropathy