Multifocal Motor Neuropathy
Conditions
Brief summary
The purpose of the study is to evaluate the efficacy (effect on grip strength and disability) and safety/tolerability of IGIV, 10% in subjects with Multifocal Motor Neuropathy.
Interventions
BIOLOGICALImmune Globulin Intravenous (human), 10%
Dose: Previous dose with 3, 4, or 6 cycles depending on previous schedule (patient specific)
BIOLOGICAL0.25% human albumin solution (Placebo)
Cross-over Period 1 (Randomized) / Cross-over Period 2 (opposite of the treatment received in Cross-over Period 1); Dose: Same volume/frequency as Stabilization Phase 1
Sponsors
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent obtained from the participant prior to any study-related procedures and study product administration * Diagnosis of definite or probable MMN based on the criteria of the American Association of Electrodiagnostic Medicine (AAEM) (Olney et al., 2003, see Section 15.1 for the full length publication). Conduction block can be identified by a drop in amplitude. Diagnosis can be based on chart records a) Hand grip (finger flexor) weakness of Medical Research Council (MRC) grade 4 or less at disease onset or appearing prior to screening; b) No upper motor signs c) No bulbar or cranial signs or symptoms; d) No clinically identifiable sensory abnormalities * Must be on a stable regimen of IGIV for at least 3 months prior to first study product administration * Treatment interval with IGIV of 2 to 5 weeks (+/- 3 days) * Dose of IGIV to be 0.4 to 2.0 g per kg BW and infusion cycle * Participants are adults, male or female, at least 18 years of age * If female and capable of bearing children - have a negative urine pregnancy test result at enrollment and agree to employ adequate birth control measures for the duration of the study * Ability and willingness to travel to the study site for infusions and assessments if required by the protocol
Exclusion criteria
* Any clinical or electrophysiological evidence of coexisting neuropathy which may interfere with outcome assessments, such as diabetic neuropathy, toxic neuropathy, or neuropathy due to systemic lupus erythematosus * Treatment with other immunosuppressive agents besides IGIV, which has demonstrated efficacy in MMN such as cyclophosphamide during the 3 months prior to enrollment (or treatment with Rituximab during the 12 months prior to enrollment). Pre-study treatment with mycophenolate mofetil or azathioprine is permitted if the dose has been stable for 3 months prior to enrollment. * Cerebrospinal fluid protein \> 100 mg/dL (if done as part of a previous evaluation) * Participants positive at enrollment for one or more of the following: Hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for Hepatitis C (HCV), PCR for human immunodeficiency virus (HIV) Type 1 * Participants with levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal for the testing laboratory * Participants with neutropenia (defined as an absolute neutrophil count \[ANC\]≤1000/mm\^3) * Participants with serum creatinine levels greater than 1.5 times the upper limit of normal for age and gender * Participants with malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * Participants with a history of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident) * Participants who received any blood or blood product exposure other than an IGIV, subcutaneous immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to enrollment * Participants with an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV or human albumin * Participants with immunoglobulin A (IgA) deficiency and known anti IgA antibodies * Participants using another investigational product or device within 30 days prior to enrollment * Participants who are unable or unwilling to meet all the requirements of this study * If female, is pregnant or lactating at time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grip Strength in the More Affected Hand | 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 | 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. |
| Mean Relative Change in Grip Strength in the More Affected Hand | 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) | 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. |
| Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs | 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 | GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment. |
| Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS) | 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) | GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment. |
| Rate of Temporally Associated Adverse Events (AEs) Per Infusion | 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) | 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. |
| 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 | Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | — |
| The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason | Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | — |
| 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 | 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) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand | 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 | 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. |
| Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand | 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) | 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. |
| Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand | 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 | 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. |
| Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand | 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) | 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. |
| Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | 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 | 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. |
| Percentage of Participants With at Least a 30% Decline in Relative Grip Strength in the More Affected Hand (Measured Using a DynEx Digital Dynamometer) | 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) | 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. |
| Rate of Related AEs Per Infusion | Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | 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. |
| Rate of Related SAEs Per Infusion | Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | 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. |
| 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 | Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | — |
| The Proportion of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs | Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | — |
| The Proportion of Infusions Associated With One or More AEs Related to the Study Product | Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | — |
| Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | 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) | 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. |
| Grip Strength in the Less Affected Hand | 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 | 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. |
| Mean Relative Change in Grip Strength in the Less Affected Hand | 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) | 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. |
| Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%) | During the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4) | 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. |
| Patient Global Impression of Change | 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 | 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 |
| Overall Disability Sum Score | 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 | 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). |
| Overall Disability Sum Score - Standardized | 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 | 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. |
| Mean Relative Change in Overall Disability Sum Score | 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) | 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. |
Countries
Canada, Denmark, United States
Participant flow
Recruitment details
Recruitment was conducted in the U.S., Canada, and Europe at 17 study sites. The first participant was enrolled in August 2008.
Pre-assignment details
Fifty unique potential participants were enrolled at clinical study sites in North America and Europe. Six were screen failures. Therefore, 44 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| All Study 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) | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 51.64 years STANDARD_DEVIATION 10.25 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 44 | 33 / 43 |
| serious Total, serious adverse events | 2 / 44 | 0 / 43 |
Outcome results
Primary
Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs
GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | 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 |
| Before Stabilization 1 | 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 |
| End of Stabilization 1 | 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 |
| End of Stabilization 1 | 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 |
| End of Cross-Over 1 | 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 |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | 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 |
| End of Stabilization 2 | 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 |
| End of Cross-Over 2 | Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 2.5 Scores on a scale |
| End of Cross-Over 2 | 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 |
| End of Stabilization 3 | 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 |
| End of Stabilization 3 | 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 |
| End of the Study | 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 |
| End of the Study | 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 |
Primary
Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS)
GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS) | 4.8 Proportion of participants |
| End of Stabilization 1 | Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS) | 35.7 Proportion of participants |
| End of Cross-Over 1 | Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS) | 11.9 Proportion of participants |
| End of Stabilization 2 | Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS) | 47.6 Proportion of participants |
p-value: 0.021McNemar
Primary
Grip Strength in the More Affected Hand
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.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | Grip Strength in the More Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 18.14 kilograms |
| Before Stabilization 1 | Grip Strength in the More Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 13.17 kilograms |
| End of Stabilization 1 | Grip Strength in the More Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 21.68 kilograms |
| End of Stabilization 1 | Grip Strength in the More Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 14.17 kilograms |
| End of Cross-Over 1 | Grip Strength in the More Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 19.54 kilograms |
| End of Cross-Over 1 | Grip Strength in the More Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 8.38 kilograms |
| End of Stabilization 2 | Grip Strength in the More Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 19.39 kilograms |
| End of Stabilization 2 | Grip Strength in the More Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 14.18 kilograms |
| End of Cross-Over 2 | Grip Strength in the More Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 11.28 kilograms |
| End of Cross-Over 2 | Grip Strength in the More Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 15.98 kilograms |
| End of Stabilization 3 | Grip Strength in the More Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 17.77 kilograms |
| End of Stabilization 3 | Grip Strength in the More Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 14.28 kilograms |
| End of the Study | Grip Strength in the More Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 17.37 kilograms |
| End of the Study | Grip Strength in the More Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 14.00 kilograms |
Primary
Mean Relative Change in Grip Strength in the More Affected Hand
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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Stabilization 1 | Mean Relative Change in Grip Strength in the More Affected Hand | -16.36 Percent change in grip strength |
| End of Stabilization 1 | Mean Relative Change in Grip Strength in the More Affected Hand | -30.52 Percent change in grip strength |
| End of Cross-Over 1 | Mean Relative Change in Grip Strength in the More Affected Hand | -30.11 Percent change in grip strength |
| End of Stabilization 2 | Mean Relative Change in Grip Strength in the More Affected Hand | 23.86 Percent change in grip strength |
p-value: 0.00595% CI: [8.81, 61.46]ANOVA
Primary
Rate of Temporally Associated Adverse Events (AEs) Per Infusion
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | Rate of Temporally Associated Adverse Events (AEs) Per Infusion | 11.5 Percentage of AEs per infusion |
| End of Stabilization 1 | Rate of Temporally Associated Adverse Events (AEs) Per Infusion | 13.2 Percentage of AEs per infusion |
| End of Cross-Over 1 | Rate of Temporally Associated Adverse Events (AEs) Per Infusion | 24.6 Percentage of AEs per infusion |
| End of Stabilization 2 | Rate of Temporally Associated Adverse Events (AEs) Per Infusion | 11.6 Percentage of AEs per infusion |
Primary
The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason | 2.9 percentage of infusions |
| End of Stabilization 1 | The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason | 0.0 percentage of infusions |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason | 0.7 percentage of infusions |
Primary
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
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | 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 | 9.1 percentage of participants |
| End of Stabilization 1 | 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 | 0.0 percentage of participants |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | 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 |
Primary
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
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | 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 | 4.5 percentage of participants |
| End of Stabilization 1 | 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 | 27.3 percentage of participants |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | 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 | 4.8 percentage of participants |
Secondary
Grip Strength in the Less Affected Hand
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.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | Grip Strength in the Less Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 27.98 kilograms |
| Before Stabilization 1 | Grip Strength in the Less Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 27.23 kilograms |
| End of Stabilization 1 | Grip Strength in the Less Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 29.52 kilograms |
| End of Stabilization 1 | Grip Strength in the Less Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 28.23 kilograms |
| End of Cross-Over 1 | Grip Strength in the Less Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 29.79 kilograms |
| End of Cross-Over 1 | Grip Strength in the Less Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 20.28 kilograms |
| End of Stabilization 2 | Grip Strength in the Less Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 29.17 kilograms |
| End of Stabilization 2 | Grip Strength in the Less Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 26.92 kilograms |
| End of Cross-Over 2 | Grip Strength in the Less Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 26.58 kilograms |
| End of Cross-Over 2 | Grip Strength in the Less Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 27.35 kilograms |
| End of Stabilization 3 | Grip Strength in the Less Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 28.97 kilograms |
| End of Stabilization 3 | Grip Strength in the Less Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 25.72 kilograms |
| End of the Study | Grip Strength in the Less Affected Hand | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 29.68 kilograms |
| End of the Study | Grip Strength in the Less Affected Hand | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 24.98 kilograms |
Secondary
Mean Relative Change in Grip Strength in the Less Affected Hand
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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Stabilization 1 | Mean Relative Change in Grip Strength in the Less Affected Hand | -2.52 Percent change in grip strength |
| End of Stabilization 1 | Mean Relative Change in Grip Strength in the Less Affected Hand | -17.96 Percent change in grip strength |
| End of Cross-Over 1 | Mean Relative Change in Grip Strength in the Less Affected Hand | -29.22 Percent change in grip strength |
| End of Stabilization 2 | Mean Relative Change in Grip Strength in the Less Affected Hand | 19.67 Percent change in grip strength |
p-value: <0.00195% CI: [14.01, 51.06]ANOVA
Secondary
Mean Relative Change in Overall Disability Sum Score
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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Stabilization 1 | Mean Relative Change in Overall Disability Sum Score | -3.14 percent change in score |
| End of Stabilization 1 | Mean Relative Change in Overall Disability Sum Score | -5.77 percent change in score |
| End of Cross-Over 1 | Mean Relative Change in Overall Disability Sum Score | -8.46 percent change in score |
| End of Stabilization 2 | Mean Relative Change in Overall Disability Sum Score | 0.92 percent change in score |
p-value: 0.00295% CI: [2.14, 9.92]ANOVA
Secondary
Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS)
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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Stabilization 1 | Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | 140.92 Percent change in assessment |
| End of Stabilization 1 | Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | 321.75 Percent change in assessment |
| End of Cross-Over 1 | Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | 258.09 Percent change in assessment |
| End of Stabilization 2 | Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | 5.75 Percent change in assessment |
p-value: 0.05995% CI: [-490.41, 57.22]ANOVA
Secondary
Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand
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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Stabilization 1 | Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand | -2.57 Percent change in time |
| End of Stabilization 1 | Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand | 3.90 Percent change in time |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand | 4.89 Percent change in time |
p-value: <0.00195% CI: [-24.37, -6.77]ANOVA
Secondary
Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand
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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Stabilization 1 | Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand | 4.78 Percent change in time |
| End of Stabilization 1 | Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand | 13.06 Percent change in time |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand | 8.56 Percent change in time |
p-value: <0.00195% CI: [-38.96, -13.26]ANOVA
Secondary
Overall Disability Sum Score
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).
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | Overall Disability Sum Score | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 3 Scores on a scale |
| Before Stabilization 1 | Overall Disability Sum Score | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 3 Scores on a scale |
| End of Stabilization 1 | Overall Disability Sum Score | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 2 Scores on a scale |
| End of Stabilization 1 | Overall Disability Sum Score | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 3 Scores on a scale |
| End of Cross-Over 1 | Overall Disability Sum Score | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 4 Scores on a scale |
| End of Cross-Over 1 | Overall Disability Sum Score | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 3 Scores on a scale |
| End of Stabilization 2 | Overall Disability Sum Score | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 3 Scores on a scale |
| End of Stabilization 2 | Overall Disability Sum Score | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 2 Scores on a scale |
| End of Cross-Over 2 | Overall Disability Sum Score | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 3 Scores on a scale |
| End of Cross-Over 2 | Overall Disability Sum Score | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 3 Scores on a scale |
| End of Stabilization 3 | Overall Disability Sum Score | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 2 Scores on a scale |
| End of Stabilization 3 | Overall Disability Sum Score | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 4 Scores on a scale |
| End of the Study | Overall Disability Sum Score | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 3 Scores on a scale |
| End of the Study | Overall Disability Sum Score | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 2 Scores on a scale |
Secondary
Overall Disability Sum Score - Standardized
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.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | Overall Disability Sum Score - Standardized | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 75.0 Scores on a scale |
| Before Stabilization 1 | Overall Disability Sum Score - Standardized | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 75.0 Scores on a scale |
| End of Stabilization 1 | Overall Disability Sum Score - Standardized | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 83.3 Scores on a scale |
| End of Stabilization 1 | Overall Disability Sum Score - Standardized | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 75.0 Scores on a scale |
| End of Cross-Over 1 | Overall Disability Sum Score - Standardized | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 79.2 Scores on a scale |
| End of Cross-Over 1 | Overall Disability Sum Score - Standardized | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 66.7 Scores on a scale |
| End of Stabilization 2 | Overall Disability Sum Score - Standardized | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 83.3 Scores on a scale |
| End of Stabilization 2 | Overall Disability Sum Score - Standardized | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 75.0 Scores on a scale |
| End of Cross-Over 2 | Overall Disability Sum Score - Standardized | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 75.0 Scores on a scale |
| End of Cross-Over 2 | Overall Disability Sum Score - Standardized | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 75.0 Scores on a scale |
| End of Stabilization 3 | Overall Disability Sum Score - Standardized | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 83.3 Scores on a scale |
| End of Stabilization 3 | Overall Disability Sum Score - Standardized | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 66.7 Scores on a scale |
| End of the Study | Overall Disability Sum Score - Standardized | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 83.3 Scores on a scale |
| End of the Study | Overall Disability Sum Score - Standardized | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 75.0 Scores on a scale |
Secondary
Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS)
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.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 4.95 Scores on a scale |
| Before Stabilization 1 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 4.80 Scores on a scale |
| End of Stabilization 1 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 2.95 Scores on a scale |
| End of Stabilization 1 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 3.15 Scores on a scale |
| End of Cross-Over 1 | 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 |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 3.50 Scores on a scale |
| End of Stabilization 2 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 5.10 Scores on a scale |
| End of Cross-Over 2 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 4.60 Scores on a scale |
| End of Cross-Over 2 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 6.85 Scores on a scale |
| End of Stabilization 3 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 4.50 Scores on a scale |
| End of Stabilization 3 | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 4.50 Scores on a scale |
| End of the Study | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | IGIV then Placebo (N= 22, 22, 22, 22, 22, 17, 21) | 3.70 Scores on a scale |
| End of the Study | Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) | Placebo then IGIV (N= 22, 22, 20, 21, 21, 19, 22) | 5.15 Scores on a scale |
Secondary
Patient Global Impression of Change
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
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | Patient Global Impression of Change | IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21) | 4.0 Scores on a scale |
| Before Stabilization 1 | Patient Global Impression of Change | Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22) | 4.0 Scores on a scale |
| End of Stabilization 1 | Patient Global Impression of Change | IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21) | 4.0 Scores on a scale |
| End of Stabilization 1 | Patient Global Impression of Change | Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22) | 6.0 Scores on a scale |
| End of Cross-Over 1 | Patient Global Impression of Change | IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21) | 4.0 Scores on a scale |
| End of Cross-Over 1 | Patient Global Impression of Change | Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22) | 3.0 Scores on a scale |
| End of Stabilization 2 | Patient Global Impression of Change | IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21) | 5.0 Scores on a scale |
| End of Stabilization 2 | Patient Global Impression of Change | Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22) | 4.0 Scores on a scale |
| End of Cross-Over 2 | Patient Global Impression of Change | IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21) | 2.0 Scores on a scale |
| End of Cross-Over 2 | Patient Global Impression of Change | Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22) | 4.0 Scores on a scale |
| End of Stabilization 3 | Patient Global Impression of Change | IGIV, 10% then Placebo (N= 22, 22, 22, 21, 17, 21) | 4.0 Scores on a scale |
| End of Stabilization 3 | Patient Global Impression of Change | Placebo then IGIV, 10% (N= 22, 20, 21, 21, 19, 22) | 4.0 Scores on a scale |
Secondary
Percentage of Participants With at Least a 30% Decline in Relative Grip Strength in the More Affected Hand (Measured Using a DynEx Digital Dynamometer)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | 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 |
| End of Stabilization 1 | Percentage of Participants With at Least a 30% Decline in Relative Grip Strength in the More Affected Hand (Measured Using a DynEx Digital Dynamometer) | 42.9 Percentage of participants |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | Percentage of Participants With at Least a 30% Decline in Relative Grip Strength in the More Affected Hand (Measured Using a DynEx Digital Dynamometer) | 47.6 Percentage of participants |
p-value: <0.001McNemar
Secondary
Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%) | 0.0 Proportion of participants |
| End of Stabilization 1 | Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%) | 69.0 Proportion of participants |
| End of Cross-Over 1 | Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%) | 2.4 Proportion of participants |
| End of Stabilization 2 | Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%) | 28.6 Proportion of participants |
p-value: <0.001McNemar
Secondary
Rate of Related AEs Per Infusion
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | Rate of Related AEs Per Infusion | 4.8 AEs per infusion |
| End of Stabilization 1 | Rate of Related AEs Per Infusion | 20.6 AEs per infusion |
| End of Cross-Over 1 | Rate of Related AEs Per Infusion | 44.3 AEs per infusion |
| End of Stabilization 2 | Rate of Related AEs Per Infusion | 15.9 AEs per infusion |
Secondary
Rate of Related SAEs Per Infusion
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | Rate of Related SAEs Per Infusion | 0.0 SAEs per infusion |
| End of Stabilization 1 | Rate of Related SAEs Per Infusion | 0.0 SAEs per infusion |
| End of Cross-Over 1 | Rate of Related SAEs Per Infusion | 0.0 SAEs per infusion |
| End of Stabilization 2 | Rate of Related SAEs Per Infusion | 0.7 SAEs per infusion |
Secondary
The Proportion of Infusions Associated With One or More AEs Related to the Study Product
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | The Proportion of Infusions Associated With One or More AEs Related to the Study Product | 3.8 proportion of infusions |
| End of Stabilization 1 | The Proportion of Infusions Associated With One or More AEs Related to the Study Product | 19.1 proportion of infusions |
| End of Cross-Over 1 | The Proportion of Infusions Associated With One or More AEs Related to the Study Product | 34.4 proportion of infusions |
| End of Stabilization 2 | The Proportion of Infusions Associated With One or More AEs Related to the Study Product | 13.0 proportion of infusions |
Secondary
The Proportion of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | 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 |
| End of Stabilization 1 | 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 |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | The Proportion of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs | 0.7 proportion of infusions |
Secondary
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
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | 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 |
| End of Stabilization 1 | 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 |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | 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 | 4.8 proportion of participants |
Secondary
Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand
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.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | 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) | 20.75 Seconds |
| Before Stabilization 1 | 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) | 26.75 Seconds |
| End of Stabilization 1 | 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) | 25.25 Seconds |
| End of Stabilization 1 | 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) | 22.00 Seconds |
| End of Cross-Over 1 | 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 |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | 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) | 24.50 Seconds |
| End of Stabilization 2 | 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) | 21.00 Seconds |
| End of Cross-Over 2 | 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) | 20.50 Seconds |
| End of Cross-Over 2 | 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) | 25.00 Seconds |
| End of Stabilization 3 | 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) | 20.50 Seconds |
| End of Stabilization 3 | 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) | 27.50 Seconds |
| End of the Study | 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) | 26.25 Seconds |
| End of the Study | 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) | 20.00 Seconds |
Secondary
Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand
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.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Stabilization 1 | 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) | 25.75 Seconds |
| Before Stabilization 1 | 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) | 31.25 Seconds |
| End of Stabilization 1 | 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) | 22.50 Seconds |
| End of Stabilization 1 | 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) | 28.00 Seconds |
| End of Cross-Over 1 | 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 |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | 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) | 23.50 Seconds |
| End of Stabilization 2 | 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) | 31.50 Seconds |
| End of Cross-Over 2 | 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) | 25.25 Seconds |
| End of Cross-Over 2 | 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) | 32.50 Seconds |
| End of Stabilization 3 | 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) | 21.00 Seconds |
| End of Stabilization 3 | 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) | 30.00 Seconds |
| End of the Study | 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) | 23.00 Seconds |
| End of the Study | 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) | 30.00 Seconds |
Post Hoc
Proportion of Participants With at Least a 30% Decline in Relative Grip Strength in the Less Affected Hand (Measured Using a DynEx Digital Dynamometer)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Before Stabilization 1 | Proportion of Participants With at Least a 30% Decline in Relative Grip Strength in the Less Affected Hand (Measured Using a DynEx Digital Dynamometer) | 0.0 Proportion of participants |
| End of Stabilization 1 | Proportion of Participants With at Least a 30% Decline in Relative Grip Strength in the Less Affected Hand (Measured Using a DynEx Digital Dynamometer) | 31.0 Proportion of participants |
| End of Cross-Over 1 | 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 |
| End of Stabilization 2 | Proportion of Participants With at Least a 30% Decline in Relative Grip Strength in the Less Affected Hand (Measured Using a DynEx Digital Dynamometer) | 66.7 Proportion of participants |
p-value: <0.001McNemar