Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Conditions
Brief summary
This study is an extension study to the pivotal study IgPro20\_3003 (NCT01545076). The purpose of this extension study is to investigate the long-term treatment of CIDP with IgPro20, with regard to safety and efficacy. Subjects who have completed subcutaneous (SC) Week 25 or were successfully rescued from a CIDP relapse during the SC Treatment Period of pivotal study IgPro20\_3003 (NCT01545076) will have the option to receive open-label low-dose IgPro20 (0.2 g/kg bodyweight \[bw\]) weekly for up to 48 weeks. Subjects relapsing on low-dose IgPro20 will either return to high-dose IgPro20 (0.4 g/kg) immediately or be discontinued, depending on investigator's judgment. Subjects returning to high-dose IgPro20 will continue on high-dose until they have completed a total of 48 weeks of IgPro20 treatment. If subjects do not successfully recover from CIDP relapse within 4 weeks, they will be withdrawn. The treatment duration will be up to 48 weeks, followed by a completion visit (week 49).
Interventions
BIOLOGICALIgPro20
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects having completed the pivotal study IgPro20\_3003 (SC Week 25) or successfully rescued from a CIDP relapse during the SC Treatment Period of pivotal study IgPro20\_3003 (NCT01545076). * Written informed consent for study participation obtained before undergoing any study-specific procedures.
Exclusion criteria
* Subject is unable to directly transition from study IgPro20\_3003. * New medical condition and/or social behavior (ie, alcohol, drug, or medication abuse) during participation in study IgPro20\_3003 that in the judgment of the investigator could increase risk to the subject, interfere with the evaluation of investigational medicinal product, and/or conduct of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Adverse Events (AEs) Per Infusion | Up to 49 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Score | Baseline and up to 49 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 From Baseline in Medical Research Council (MRC) Score | Baseline and up to 49 weeks | An adapted version of the MRC sum score as published by Kleyweg and the RMC trial group was used. With the MRC sum score, the following 8 bilateral muscle pairs were assessed, and individual muscle scores as well as the sum score documented: Shoulder abduction; Elbow flexion; Wrist extension; Index finger abduction; Hip flexion; Knee extension; Foot dorsiflexion; Great toe dorsiflexion. The MRC sum score ranges from 0 (paralysis) to 80 (normal strength) points. |
| Change From Baseline in Rasch-built Overall Disability Scale (R-ODS) | Baseline and up to 49 weeks | The R-ODS is a recently published outcome measure that captures activity and social participation in subjects with Guillain-Barré Syndrome, CIDP, and monoclonal gammopathy of uncertain significance. The 24-item questionnaire covers a wide range of tasks of daily life that are each to be rated as impossible to perform, able to perform with difficulty, or easy to perform (scale of 0 - 2 points respectively). Items are sorted in order of increasing difficulty to perform, based on data from subjects with peripheral neuropathies (chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome, or monoclonal gammopathy of uncertain significance) and subjects recruited at the university outpatient clinics of Rotterdam and Maastricht. |
| Change From Baseline in Mean Grip Strength | Baseline and up to 49 weeks | The hand-held Vigorimeter from Martin (Tuttlingen, Germany) is a device that measures the strength of small muscles in the hand, ie, grip strength. The subject squeezes a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure is recorded via a rubber tube on a nanometer and expressed in kilopascal (kPa). At each assessment, the subject squeezes 3 times with each hand. |
| Percentage of Subjects With Adverse Events (AEs) | Up to 49 weeks | — |
| Time to First CIDP Relapse | Up to 49 weeks | Time to first CIDP relapse based on adjusted INCAT score, using the Kaplan-Meier estimator. 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 only). |
| Percentage of Subjects With AEs by Severity | Up to 49 weeks | — |
| Number of Causally Related AEs Per Infusion | Up to 49 weeks | — |
| Percentage of Subjects With Causally Related AEs | Up to 49 weeks | — |
| Number of Serious AEs Per Infusion | Up to 49 weeks | — |
| Percentage of Subjects With Serious AEs | Up to 49 weeks | — |
| Number of AEs by Severity Per Infusion | Up to 49 weeks | — |
Countries
Australia, Canada, Czechia, France, Germany, Italy, Japan, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IgPro20 20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly at 0.2 g/kg or 0.4 g/kg. | 82 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | IgPro20 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 27 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants |
| Age, Continuous | 57.57 years STANDARD_DEVIATION 13.224 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 70 Participants |
| Region of Enrollment Australia | 1 participants |
| Region of Enrollment Canada | 7 participants |
| Region of Enrollment Czechia | 2 participants |
| Region of Enrollment France | 1 participants |
| Region of Enrollment Germany | 29 participants |
| Region of Enrollment Italy | 8 participants |
| Region of Enrollment Japan | 10 participants |
| Region of Enrollment Netherlands | 1 participants |
| Region of Enrollment Spain | 10 participants |
| Region of Enrollment United Kingdom | 4 participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 82 |
| other Total, other adverse events | 25 / 82 |
| serious Total, serious adverse events | 7 / 82 |
Outcome results
Primary
Number of Adverse Events (AEs) Per Infusion
Time frame: Up to 49 weeks
Population: Safety Data Set (SDS): all subjects who received at least 1 dose of IgPro20 in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Adverse Events (AEs) Per Infusion | 0.032 Adverse events per infusion |
Secondary
Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) 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: Baseline and up to 49 weeks
Population: Total Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Score | 0.0 units on a scale |
Secondary
Change From Baseline in Mean Grip Strength
The hand-held Vigorimeter from Martin (Tuttlingen, Germany) is a device that measures the strength of small muscles in the hand, ie, grip strength. The subject squeezes a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure is recorded via a rubber tube on a nanometer and expressed in kilopascal (kPa). At each assessment, the subject squeezes 3 times with each hand.
Time frame: Baseline and up to 49 weeks
Population: Total Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Change From Baseline in Mean Grip Strength | -0.7 kPa |
Secondary
Change From Baseline in Medical Research Council (MRC) Score
An adapted version of the MRC sum score as published by Kleyweg and the RMC trial group was used. With the MRC sum score, the following 8 bilateral muscle pairs were assessed, and individual muscle scores as well as the sum score documented: Shoulder abduction; Elbow flexion; Wrist extension; Index finger abduction; Hip flexion; Knee extension; Foot dorsiflexion; Great toe dorsiflexion. The MRC sum score ranges from 0 (paralysis) to 80 (normal strength) points.
Time frame: Baseline and up to 49 weeks
Population: Total Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Change From Baseline in Medical Research Council (MRC) Score | 0.0 units on a scale |
Secondary
Change From Baseline in Rasch-built Overall Disability Scale (R-ODS)
The R-ODS is a recently published outcome measure that captures activity and social participation in subjects with Guillain-Barré Syndrome, CIDP, and monoclonal gammopathy of uncertain significance. The 24-item questionnaire covers a wide range of tasks of daily life that are each to be rated as impossible to perform, able to perform with difficulty, or easy to perform (scale of 0 - 2 points respectively). Items are sorted in order of increasing difficulty to perform, based on data from subjects with peripheral neuropathies (chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome, or monoclonal gammopathy of uncertain significance) and subjects recruited at the university outpatient clinics of Rotterdam and Maastricht.
Time frame: Baseline and up to 49 weeks
Population: Total Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Change From Baseline in Rasch-built Overall Disability Scale (R-ODS) | 0.0 units on a scale |
Secondary
Number of AEs by Severity Per Infusion
Time frame: Up to 49 weeks
Population: SDS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Number of AEs by Severity Per Infusion | Mild | 0.024 Adverse events per infusion |
| IgPro20 | Number of AEs by Severity Per Infusion | Moderate | 0.006 Adverse events per infusion |
| IgPro20 | Number of AEs by Severity Per Infusion | Severe | 0.002 Adverse events per infusion |
Secondary
Number of Causally Related AEs Per Infusion
Time frame: Up to 49 weeks
Population: SDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Causally Related AEs Per Infusion | 0.011 Adverse events per infusion |
Secondary
Number of Serious AEs Per Infusion
Time frame: Up to 49 weeks
Population: SDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Serious AEs Per Infusion | 0.001 Adverse events per infusion |
Secondary
Percentage of Subjects With Adverse Events (AEs)
Time frame: Up to 49 weeks
Population: SDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Percentage of Subjects With Adverse Events (AEs) | 75.6 percentage of subjects |
Secondary
Percentage of Subjects With AEs by Severity
Time frame: Up to 49 weeks
Population: SDS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Percentage of Subjects With AEs by Severity | Mild | 62.2 percentage of subjects |
| IgPro20 | Percentage of Subjects With AEs by Severity | Moderate | 29.3 percentage of subjects |
| IgPro20 | Percentage of Subjects With AEs by Severity | Severe | 9.8 percentage of subjects |
Secondary
Percentage of Subjects With Causally Related AEs
Time frame: Up to 49 weeks
Population: SDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Percentage of Subjects With Causally Related AEs | 25.6 percentage of subjects |
Secondary
Percentage of Subjects With Serious AEs
Time frame: Up to 49 weeks
Population: SDS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Percentage of Subjects With Serious AEs | 8.5 percentage of subjects |
Secondary
Time to First CIDP Relapse
Time to first CIDP relapse based on adjusted INCAT score, using the Kaplan-Meier estimator. 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 only).
Time frame: Up to 49 weeks
Population: Total Set: all subjects enrolled in the study, ie, the subject's informed consent was obtained. In the study protocol, this analysis set was referred to as the Intention-to-Treat Data Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Time to First CIDP Relapse | 266.0 Days |