Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20)
- Conditions
- Chronic Inflammatory Demyelinating PolyneuropathyPolyradiculoneuropathy
- Interventions
- Biological: IgPro10Biological: IgPro20 (low dose)Biological: PlaceboBiological: IgPro20 (high dose)
- Registration Number
- NCT01545076
- Lead Sponsor
- CSL Behring
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 208
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IgPro20 high dose IgPro10 - IgPro20 low dose IgPro10 - IgPro20 high dose IgPro20 (high dose) - IgPro20 low dose IgPro20 (low dose) - Placebo Placebo - Placebo IgPro10 -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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.
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 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).
Number of Adverse Events Per IgPro10 Infusion During Re-stabilization Therapy Up to 13 weeks Number of Subjects With Adverse Events During IgPro10 Rescue Therapy Up to 13 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.
Number of Adverse Events Per IgPro10 Infusion During Rescue Therapy Up to 13 weeks Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy Up to 13 weeks Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period Up to 25 weeks 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 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.
Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy Up to 13 weeks 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.
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 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.
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 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 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.
Trial Locations
- Locations (91)
Site Reference 1240048
🇨🇦Vancouver, British Columbia, Canada
Site reference 2760053
🇩🇪Göttingen, Germany
Site reference 1240007
🇨🇦Quebec, Canada
Site Reference 8400268
🇺🇸Charlottesville, Virginia, United States
Site reference 2760049
🇩🇪Bochum, Germany
Site reference 1240006
🇨🇦Edmonton, Canada
Site reference 2760072
🇩🇪Berlin, Germany
Site reference 2460002
🇫🇮Helsinki, Finland
Site reference 2500024
🇫🇷Clermont-Ferrand, France
Site reference 2500022
🇫🇷Nice, France
Site reference 2030003
🇨🇿Prague, Czechia
Site reference 2500019
🇫🇷Pessac, France
Site Reference 2760113
🇩🇪Ibbenbueren, Germany
Site Reference 0360017
🇦🇺Herston, Queensland, Australia
Site reference 2030009
🇨🇿Hradec Kralove, Czechia
Site Reference 2330002
🇪🇪Tallinn, Estonia
Site reference 3800027
🇮🇹Firenze, Italy
Site reference 3800031
🇮🇹Milano, Italy
Site reference 3800035
🇮🇹Roma, Italy
Site reference 2760075
🇩🇪Duesseldorf, Germany
Site reference 0360008
🇦🇺Southport, Australia
Site reference 1240009
🇨🇦Toronto, Canada
Site reference 2760054
🇩🇪Hannover, Germany
Site reference 0360011
🇦🇺Fitzroy, Victoria, Australia
Site reference 0560003
🇧🇪Leuven, Belgium
Site reference 7240010
🇪🇸Barcelona, Spain
Site reference 2500013
🇫🇷Marseille, France
Site Reference 8260032
🇬🇧Manchester, United Kingdom
Site reference 7240013
🇪🇸Madrid, Spain
Site reference 7240014
🇪🇸Madrid, Spain
Site reference 3800028
🇮🇹Genova, Italy
Site reference 2760048
🇩🇪Berlin, Germany
Site Reference 2330003
🇪🇪Tallinn, Estonia
Site reference 2760069
🇩🇪Berlin, Germany
Site Reference 2760094
🇩🇪Essen, Germany
Site reference 2030002
🇨🇿Hradec Kralove, Czechia
Site reference 3800026
🇮🇹Chieti, Italy
Site reference 2760039
🇩🇪Wuerzburg, Germany
Site reference 3800036
🇮🇹Roma, Italy
Site reference 7240011
🇪🇸Barcelona, Spain
Site reference 2760047
🇩🇪Potsdam, Germany
Site reference 3920034
🇯🇵Tokushima, Japan
Site Reference 6160055
🇵🇱Lublin, Poland
Site reference 7240016
🇪🇸Sevilla, Spain
Site reference 8260019
🇬🇧London, United Kingdom
Site reference 3800037
🇮🇹Torino, Italy
Site reference 3920038
🇯🇵Chiba, Japan
Site Reference 8400340
🇺🇸Seattle, Washington, United States
Site reference 8400181
🇺🇸Birmingham, Alabama, United States
Site reference 8400173
🇺🇸Phoenix, Arizona, United States
Site reference 8400077
🇺🇸Centennial, Colorado, United States
Site reference 8400167
🇺🇸Los Angeles, California, United States
Site Reference 8400352
🇺🇸Washington, District of Columbia, United States
Site reference 8400214
🇺🇸Miami, Florida, United States
Site Reference 8400247
🇺🇸Chicago, Illinois, United States
Site reference 8400162
🇺🇸Chicago, Illinois, United States
Site Reference 8400215
🇺🇸Indianapolis, Indiana, United States
Site reference 8400166
🇺🇸Kansas City, Kansas, United States
Site Reference 8400347
🇺🇸New Brunswick, New Jersey, United States
Site reference 8400169
🇺🇸New York, New York, United States
Site reference 8400179
🇺🇸New York, New York, United States
Site reference 8400182
🇺🇸Charlotte, North Carolina, United States
Site reference 8400178
🇺🇸Columbus, Ohio, United States
Site Reference 8400346
🇺🇸Durham, North Carolina, United States
Site reference 8400217
🇺🇸Oklahoma City, Oklahoma, United States
Site reference 8400164
🇺🇸Houston, Texas, United States
Site reference 3800030
🇮🇹Rozzano, Italy
Site reference 3760005
🇮🇱Haifa, Israel
Site reference 3920045
🇯🇵Matsumoto, Japan
Site reference 3920058
🇯🇵Osaka, Japan
Site reference 3920032
🇯🇵Tokyo, Japan
Site reference 8400172
🇺🇸Phoenix, Arizona, United States
Site reference 3920035
🇯🇵Yamaguchi, Japan
Site reference 5280001
🇳🇱Amsterdam, Netherlands
Site Reference 3920042
🇯🇵Aomori, Japan
Site reference 3920061
🇯🇵Kanagawa, Japan
Site Reference 8400177
🇺🇸Nashville, Tennessee, United States
Site Reference 1240051
🇨🇦Montreal, Quebec, Canada
Site Reference 3920040
🇯🇵Aomori, Japan
Site Reference 3920065
🇯🇵Tokyo, Japan
Site Reference 3920062
🇯🇵Tokyo, Japan
Site reference 5280005
🇳🇱Maastricht, Netherlands
Site reference 5280004
🇳🇱Utrecht, Netherlands
Site reference 3760002
🇮🇱Tel Aviv, Israel
Site reference 3920037
🇯🇵Saitama, Japan
Site Reference 6160058
🇵🇱Gdansk, Poland
Site Reference 6160060
🇵🇱Lodz, Poland
Site reference 2760052
🇩🇪Essen, Germany
Site reference 2760080
🇩🇪Koeln, Germany
Site reference 2760036
🇩🇪Göttingen, Germany
Site reference 2760055
🇩🇪Leipzig, Germany