Chronic Inflammatory Demyelinating Polyneuropathy, Polyradiculoneuropathy
Conditions
Brief summary
This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group 3-arm study to investigate 2 different doses of subcutaneous (SC) IgPro20 compared with placebo for maintenance treatment of patients with CIDP. Patients who received at lease 1 dose of intravenous immunoglobulin (IVIG) within 8 weeks before screening will be assessed during 4 separate study periods. Patients first undergo a Screening Period, followed by an IgG Dependency Test Period of up to 12 weeks to test for ongoing need of IgG. Those patients experiencing CIDP relapse during this test period will be administered a standardized IVIG regimen during an IVIG Re-stabilization Period. Patients with improved and maintained adjusted inflammatory neuropathy cause and treatment scale (INCAT) in the IVIG Re-stabilization Period will continue to the SC Treatment Period of the study. Patients entering the 24 week SC Treatment Period will be randomized to receive weekly infusions of 1 of 2 IgPro20 doses (0.2 or 0.4 g/kg body weight) or placebo. The overall study duration is up to 52 weeks. Clinical outcomes will be assessed by the Inflammatory Neuropathy Cause and Treatment (INCAT) score, maximum grip strength, the Medical Research Council (MRC) sum score, the Rasch-built Overall Disability Scale (R-ODS), and electrophysiological evaluations.
Interventions
BIOLOGICALIgPro20 (low dose)
20% liquid formulation (200 mg/mL) of human normal immunoglobulin for subcutaneous use administered weekly during the SC treatment period of the study according to the randomization: 0.2 g/kg body weight (low dose arm)
BIOLOGICALPlacebo
2% human albumin administered by weekly SC infusions during the SC treatment period of the study.
BIOLOGICALIgPro10
10% Immunoglobulin G (IgG) liquid formulation of human normal immunoglobulin (Privigen®) administered intravenously during Restabilization Period of the study and/or as Rescue Therapy during SC Treatment Period for subjects with a CIDP relapse.
BIOLOGICALIgPro20 (high dose)
20% liquid formulation (200 mg/mL) of human normal immunoglobulin for subcutaneous use administered weekly during the SC treatment period of the study according to the randomization: 0.4 g/kg body weight (high dose arm)
Sponsors
ICON Clinical Research
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria 2010. * An IVIG treatment during the last 8 weeks prior to enrollment. * Age ≥18 years. * Written informed consent for study participation obtained before undergoing any study-specific procedures.
Exclusion criteria
* Any polyneuropathy of other causes * Any other disease (mainly neurological or chronic orthopedic) that has caused neurological symptoms or may interfere with treatment or outcome assessments * Severe diseases and conditions that are likely to interfere with evaluation of the study product or satisfactory conduct of the study * History of thrombotic episodes within the 2 years prior to enrolment * Known allergic or other severe reactions to blood products including intolerability to previous IVIG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period | Up to 25 weeks | Relapse is defined as an increase of at least 1 INCAT score point (except for the increase from 0 to 1 in the upper limb score). The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period | Baseline and up to 25 weeks | The hand-held Vigorimeter is a device that measures the strength of small muscles in the hand; ie, grip strength. Subjects squeezed a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure was recorded via a rubber tube on a nanometer and expressed in kilopascal. At each assessment, the subjects squeezed 3 times with each hand. The mean grip strength median score of the dominant hand was determined. |
| Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period | Baseline and up to 25 weeks | An adapted version of the MRC sum score was used in the study. The MRC sum score is the sum of all 16 muscle scores, and ranges from 0 (paralysis) to 80 (normal strength). |
| Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period | Baseline and up to 25 weeks | The R-ODS centile score captures activity and social participation in subjects with CIDP. The R-ODS centile score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations). |
| Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period | Up to 25 weeks | — |
| Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period | Up to 28 weeks | — |
| Number of Subjects With Adverse Events During the SC Treatment Period | Up to 28 weeks | — |
| Percentage of Subjects With Adverse Events During the SC Treatment Period | Up to 28 weeks | — |
| Time to Improvement During IgPro10 Re-stabilization Therapy | Up to 13 weeks | Improvement is defined as an INCAT score decrease by 1 point (except for the decrease from 1 to 0 in the upper limb score), R-ODS improvement by at least 4 points, Mean Grip strength improvement by at least 8 kPa in one hand, or MRC Sum score \>=3. |
| Change in Mean Grip Strength During IgPro10 Re-stabilization Therapy | Reference visit and up to 13 weeks | The hand-held Vigorimeter is a device that measures the strength of small muscles in the hand; ie, grip strength. Subjects squeezed a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure was recorded via a rubber tube on a nanometer and expressed in kilopascal. At each assessment, the subjects squeezed 3 times with each hand. The mean grip strength median score of the dominant hand was determined. |
| Change in MRC Sum Score During IgPro10 Re-stabilization Therapy | Reference visit and up to 13 weeks | An adapted version of the MRC sum score was used in the study. The MRC sum score is the sum of all 16 muscle scores, and ranges from 0 (paralysis) to 80 (normal strength). |
| Change in R-ODS During IgPro10 Re-stabilization Therapy | Reference visit and up to 13 weeks | The R-ODS centile score captures activity and social participation in subjects with CIDP. The R-ODS centile score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations). |
| Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period | Baseline and up to 25 weeks | The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant. |
| Number of Adverse Events Per IgPro10 Infusion During Re-stabilization Therapy | Up to 13 weeks | — |
| Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy | Up to 13 weeks | — |
| Percent of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy | Up to 13 weeks | — |
| Time to Improvement After CIDP Relapse During IgPro10 Rescue Therapy | Up to 13 weeks | Improvement is defined as a decrease in INCAT score (except for the decrease from 1 to 0 in the upper limb score) back to or below the baseline score..The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant. |
| Number of Adverse Events Per IgPro10 Infusion During Rescue Therapy | Up to 13 weeks | — |
| Number of Subjects With Adverse Events During IgPro10 Rescue Therapy | Up to 13 weeks | — |
| Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy | Up to 13 weeks | — |
| Change in Mean Grip Strength During IgPro10 Rescue Therapy | Before first rescue IgPro10 infusion and up to 13 weeks | The hand-held Vigorimeter is a device that measures the strength of small muscles in the hand; ie, grip strength. Subjects squeezed a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure was recorded via a rubber tube on a nanometer and expressed in kilopascal. At each assessment, the subjects squeezed 3 times with each hand. The mean grip strength median score of the dominant hand was determined. |
| Change in MRC Sum Score During IgPro10 Rescue Therapy | Before first rescue IgPro10 infusion and up to 13 weeks | An adapted version of the MRC sum score was used in the study. The MRC sum score is the sum of all 16 muscle scores, and ranges from 0 (paralysis) to 80 (normal strength). |
| Change in R-ODS During IgPro10 Rescue Therapy | Before first rescue IgPro10 infusion and up to 13 weeks | The R-ODS centile score captures activity and social participation in subjects with CIDP. The R-ODS centile score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations). |
| Change in INCAT During IgPro10 Rescue Therapy | Before first rescue IgPro10 infusion and up to 13 weeks | The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant. |
| Change in INCAT During IgPro10 Re-stabilization Therapy | Reference visit and up to 13 weeks | The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant. |
Countries
Australia, Belgium, Canada, Czechia, Estonia, Finland, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pre-randomization Safety Data Set (PSDS) Pre-randomization Safety Data Set (PSDS): The PSDS was based on all subjects enrolled into the study who received at least 1 dose of IgPro10 (in the re-stabilization period) before randomization into the subcutaneous period. One subject withdrew from the re-stabilization period prior to receiving IgPro10, therefore n=207 for the PSDS. | 207 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| IgPro10 Restabilization Period | Adverse Event | 4 | 0 | 0 | 0 | 0 |
| IgPro10 Restabilization Period | Failure to meet randomization criteria | 22 | 0 | 0 | 0 | 0 |
| IgPro10 Restabilization Period | Physician Decision | 2 | 0 | 0 | 0 | 0 |
| IgPro10 Restabilization Period | Protocol Violation | 1 | 0 | 0 | 0 | 0 |
| IgPro10 Restabilization Period | Withdrawal by Subject | 7 | 0 | 0 | 0 | 0 |
| IgPro20 Subcutaneous Treatment Period | Adverse Event | 0 | 1 | 1 | 0 | 0 |
| IgPro20 Subcutaneous Treatment Period | Lack of Efficacy | 0 | 10 | 18 | 32 | 0 |
| IgPro20 Subcutaneous Treatment Period | Physician Decision | 0 | 0 | 0 | 1 | 0 |
| IgPro20 Subcutaneous Treatment Period | Withdrawal by Subject | 0 | 8 | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Pre-randomization Safety Data Set (PSDS) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 57 Participants |
| Age, Categorical Between 18 and 65 years | 150 Participants |
| Age, Continuous | 56.5 years STANDARD_DEVIATION 12.76 |
| Region of Enrollment Australia | 6 Participants |
| Region of Enrollment Belgium | 2 Participants |
| Region of Enrollment Canada | 19 Participants |
| Region of Enrollment Czechia | 6 Participants |
| Region of Enrollment Estonia | 2 Participants |
| Region of Enrollment Finland | 1 Participants |
| Region of Enrollment France | 9 Participants |
| Region of Enrollment Germany | 51 Participants |
| Region of Enrollment Israel | 2 Participants |
| Region of Enrollment Italy | 32 Participants |
| Region of Enrollment Japan | 15 Participants |
| Region of Enrollment Netherlands | 7 Participants |
| Region of Enrollment Poland | 8 Participants |
| Region of Enrollment Spain | 16 Participants |
| Region of Enrollment United Kingdom | 6 Participants |
| Region of Enrollment United States | 25 Participants |
| Sex: Female, Male Female | 76 Participants |
| Sex: Female, Male Male | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 207 | 0 / 58 | 0 / 57 | 0 / 57 | 0 / 60 |
| other Total, other adverse events | 50 / 207 | 20 / 58 | 22 / 57 | 15 / 57 | 7 / 60 |
| serious Total, serious adverse events | 11 / 207 | 2 / 58 | 3 / 57 | 1 / 57 | 2 / 60 |
Outcome results
Primary
Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period
Relapse is defined as an increase of at least 1 INCAT score point (except for the increase from 0 to 1 in the upper limb score). The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant.
Time frame: Up to 25 weeks
Population: Intention-to-treat Set (ITTS): The ITTS consists of all randomized subjects who received at least 1 dose of IgPro20 / placebo and satisfied inclusion criterion #1 (diagnosis of CIDP).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period | 32.8 percentage of subjects |
| IgPro20 (0.2) | Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period | 38.6 percentage of subjects |
| Placebo | Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period | 63.2 percentage of subjects |
p-value: =0.00795% CI: [-40.7, -6.21]Fisher Exact
p-value: <0.00195% CI: [-46, -12.2]Fisher Exact
Secondary
Change in INCAT During IgPro10 Rescue Therapy
The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant.
Time frame: Before first rescue IgPro10 infusion and up to 13 weeks
Population: RSDS. Not all subjects from the RSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in INCAT During IgPro10 Rescue Therapy | -1.3 units on a scale | Standard Deviation 1.31 |
Secondary
Change in INCAT During IgPro10 Re-stabilization Therapy
The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant.
Time frame: Reference visit and up to 13 weeks
Population: PSDS. Not all subjects from the PSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in INCAT During IgPro10 Re-stabilization Therapy | -1.1 units on a scale | Standard Deviation 1.2 |
Secondary
Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period
The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant.
Time frame: Baseline and up to 25 weeks
Population: ITTS. Not all subjects from the ITTS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 (0.4) | Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period | 0 units on a scale |
| IgPro20 (0.2) | Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period | 0 units on a scale |
| Placebo | Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period | 1 units on a scale |
p-value: =0.00595% CI: [-1, 0]Wilcoxon rank sum
p-value: <0.00195% CI: [-1, 0]Wilcoxon rank sum
Secondary
Change in Mean Grip Strength During IgPro10 Rescue Therapy
The hand-held Vigorimeter is a device that measures the strength of small muscles in the hand; ie, grip strength. Subjects squeezed a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure was recorded via a rubber tube on a nanometer and expressed in kilopascal. At each assessment, the subjects squeezed 3 times with each hand. The mean grip strength median score of the dominant hand was determined.
Time frame: Before first rescue IgPro10 infusion and up to 13 weeks
Population: RSDS. Not all subjects from the RSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in Mean Grip Strength During IgPro10 Rescue Therapy | 16.3 kPa | Standard Deviation 17.58 |
Secondary
Change in Mean Grip Strength During IgPro10 Re-stabilization Therapy
The hand-held Vigorimeter is a device that measures the strength of small muscles in the hand; ie, grip strength. Subjects squeezed a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure was recorded via a rubber tube on a nanometer and expressed in kilopascal. At each assessment, the subjects squeezed 3 times with each hand. The mean grip strength median score of the dominant hand was determined.
Time frame: Reference visit and up to 13 weeks
Population: PSDS. Not all subjects from the PSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in Mean Grip Strength During IgPro10 Re-stabilization Therapy | 11.27 kPa | Standard Deviation 16.89 |
Secondary
Change in MRC Sum Score During IgPro10 Rescue Therapy
An adapted version of the MRC sum score was used in the study. The MRC sum score is the sum of all 16 muscle scores, and ranges from 0 (paralysis) to 80 (normal strength).
Time frame: Before first rescue IgPro10 infusion and up to 13 weeks
Population: RSDS. Not all subjects from the RSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in MRC Sum Score During IgPro10 Rescue Therapy | 6.8 units on a scale | Standard Deviation 5.28 |
Secondary
Change in MRC Sum Score During IgPro10 Re-stabilization Therapy
An adapted version of the MRC sum score was used in the study. The MRC sum score is the sum of all 16 muscle scores, and ranges from 0 (paralysis) to 80 (normal strength).
Time frame: Reference visit and up to 13 weeks
Population: PSDS. Not all subjects from the PSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in MRC Sum Score During IgPro10 Re-stabilization Therapy | 3.4 units on a scale | Standard Deviation 4.9 |
Secondary
Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period
The R-ODS centile score captures activity and social participation in subjects with CIDP. The R-ODS centile score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations).
Time frame: Baseline and up to 25 weeks
Population: ITTS. Not all subjects from the ITTS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 (0.4) | Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period | 0 units on a scale |
| IgPro20 (0.2) | Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period | -2 units on a scale |
| Placebo | Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period | -3 units on a scale |
p-value: =0.0395% CI: [0, 9]Wilcoxon rank sum
p-value: <0.00195% CI: [2, 9]Wilcoxon rank sum
Secondary
Change in R-ODS During IgPro10 Rescue Therapy
The R-ODS centile score captures activity and social participation in subjects with CIDP. The R-ODS centile score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations).
Time frame: Before first rescue IgPro10 infusion and up to 13 weeks
Population: RSDS. Not all subjects from the RSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in R-ODS During IgPro10 Rescue Therapy | 14.0 units on a scale | Standard Deviation 14.69 |
Secondary
Change in R-ODS During IgPro10 Re-stabilization Therapy
The R-ODS centile score captures activity and social participation in subjects with CIDP. The R-ODS centile score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations).
Time frame: Reference visit and up to 13 weeks
Population: PSDS. Not all subjects from the PSDS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 (0.4) | Change in R-ODS During IgPro10 Re-stabilization Therapy | 4.7 units on a scale | Standard Deviation 14.14 |
Secondary
Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period
An adapted version of the MRC sum score was used in the study. The MRC sum score is the sum of all 16 muscle scores, and ranges from 0 (paralysis) to 80 (normal strength).
Time frame: Baseline and up to 25 weeks
Population: ITTS. Not all subjects from the ITTS were available for data collection for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 (0.4) | Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period | 0 units on a scale |
| IgPro20 (0.2) | Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period | 0 units on a scale |
| Placebo | Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period | -2 units on a scale |
p-value: =0.00395% CI: [1, 4]Wilcoxon rank sum
p-value: =0.00295% CI: [1, 4]Wilcoxon rank sum
Secondary
Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period
The hand-held Vigorimeter is a device that measures the strength of small muscles in the hand; ie, grip strength. Subjects squeezed a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure was recorded via a rubber tube on a nanometer and expressed in kilopascal. At each assessment, the subjects squeezed 3 times with each hand. The mean grip strength median score of the dominant hand was determined.
Time frame: Baseline and up to 25 weeks
Population: ITTS. Not all subjects from the ITTS were available for data collection for this outcome measure..
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 (0.4) | Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period | -2.7 Kilopascal (kPa) |
| IgPro20 (0.2) | Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period | -0.6 Kilopascal (kPa) |
| Placebo | Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period | -6.6 Kilopascal (kPa) |
p-value: =0.00495% CI: [2, 14]Wilcoxon rank sum
p-value: =0.01495% CI: [0.7, 11.7]Wilcoxon rank sum
Secondary
Number of Adverse Events Per IgPro10 Infusion During Rescue Therapy
Time frame: Up to 13 weeks
Population: RSDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Number of Adverse Events Per IgPro10 Infusion During Rescue Therapy | 0.142 Adverse events/Infusion |
Secondary
Number of Adverse Events Per IgPro10 Infusion During Re-stabilization Therapy
Time frame: Up to 13 weeks
Population: PSDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Number of Adverse Events Per IgPro10 Infusion During Re-stabilization Therapy | 0.175 Adverse events/Infusion |
Secondary
Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period
Time frame: Up to 28 weeks
Population: Safety Data Set (SDS): The SDS consists of all randomized subjects who received at least 1 dose of IgPro20 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period | 0.051 Adverse events/Infusion |
| IgPro20 (0.2) | Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period | 0.079 Adverse events/Infusion |
| Placebo | Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period | 0.034 Adverse events/Infusion |
Secondary
Number of Subjects With Adverse Events During IgPro10 Rescue Therapy
Time frame: Up to 13 weeks
Population: RSDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Number of Subjects With Adverse Events During IgPro10 Rescue Therapy | 17 participants |
Secondary
Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy
Time frame: Up to 13 weeks
Population: PSDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy | 100 participants |
Secondary
Number of Subjects With Adverse Events During the SC Treatment Period
Time frame: Up to 28 weeks
Population: SDS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IgPro20 (0.4) | Number of Subjects With Adverse Events During the SC Treatment Period | 30 Participants |
| IgPro20 (0.2) | Number of Subjects With Adverse Events During the SC Treatment Period | 33 Participants |
| Placebo | Number of Subjects With Adverse Events During the SC Treatment Period | 21 Participants |
Secondary
Percentage of Subjects With Adverse Events During the SC Treatment Period
Time frame: Up to 28 weeks
Population: SDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Percentage of Subjects With Adverse Events During the SC Treatment Period | 51.7 percentage of subjects |
| IgPro20 (0.2) | Percentage of Subjects With Adverse Events During the SC Treatment Period | 57.9 percentage of subjects |
| Placebo | Percentage of Subjects With Adverse Events During the SC Treatment Period | 36.8 percentage of subjects |
Secondary
Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy
Time frame: Up to 13 weeks
Population: RSDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy | 28.3 percentage of subjects |
Secondary
Percent of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy
Time frame: Up to 13 weeks
Population: PSDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 (0.4) | Percent of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy | 48.3 percentage of subjects |
Secondary
Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period
Time frame: Up to 25 weeks
Population: ITTS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 (0.4) | Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period | NA Days |
| IgPro20 (0.2) | Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period | NA Days |
| Placebo | Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period | 79.0 Days |
Secondary
Time to Improvement After CIDP Relapse During IgPro10 Rescue Therapy
Improvement is defined as a decrease in INCAT score (except for the decrease from 1 to 0 in the upper limb score) back to or below the baseline score..The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 (No upper limb problems) to 5 (Inability to use either arm for any purposeful movement), and scores for leg disability range from 0 (Walking not affected) to 5 (Restricted to wheelchair, unable to stand and walk a few steps with help). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the adjusted INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant.
Time frame: Up to 13 weeks
Population: Rescue Medication Safety Data Set (RSDS): The RSDS consists of subjects of the SDS who received at least 1 dose of IgPro10 rescue medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 (0.4) | Time to Improvement After CIDP Relapse During IgPro10 Rescue Therapy | 23 Days |
Secondary
Time to Improvement During IgPro10 Re-stabilization Therapy
Improvement is defined as an INCAT score decrease by 1 point (except for the decrease from 1 to 0 in the upper limb score), R-ODS improvement by at least 4 points, Mean Grip strength improvement by at least 8 kPa in one hand, or MRC Sum score \>=3.
Time frame: Up to 13 weeks
Population: Pre-randomization Safety Data Set (PSDS): The PSDS was based on all subjects enrolled into the study who received at least 1 dose of IgPro10 (in the re-stabilization period) before randomization into the subcutaneous period. One subject withdrew from the re-stabilization period prior to receiving IgPro10, therefore n=207 for the PSDS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 (0.4) | Time to Improvement During IgPro10 Re-stabilization Therapy | 23 Days |