Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01545076 |
|
Recruitment Status :
Completed
First Posted : March 6, 2012
Results First Posted : July 5, 2018
Last Update Posted : July 5, 2018
|
Sponsor:
CSL Behring
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
CSL Behring
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Inflammatory Demyelinating Polyneuropathy Polyradiculoneuropathy | Biological: IgPro20 (low dose) Biological: Placebo Biological: IgPro10 Biological: IgPro20 (high dose) | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 208 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group Phase III Study to Investigate the Efficacy, Safety, and Tolerability of 2 Different Doses of IgPro20 (Subcutaneous Immunoglobulin) for the Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) - the PATH Study |
| Study Start Date : | March 2012 |
| Actual Primary Completion Date : | September 2016 |
| Actual Study Completion Date : | September 2016 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Globulin, Immune
| Arm | Intervention/treatment |
|---|---|
| Experimental: IgPro20 low dose |
Biological: IgPro20 (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) Other Name: Hizentra Biological: IgPro10 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. |
| Experimental: IgPro20 high dose |
Biological: IgPro10
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. Biological: IgPro20 (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) Other Name: Hizentra |
| Placebo Comparator: Placebo |
Biological: Placebo
2% human albumin administered by weekly SC infusions during the SC treatment period of the study. Biological: IgPro10 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. |
Primary Outcome Measures :
- Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period [ Time Frame: 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 :
- Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 25 weeks ]
- Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period [ Time Frame: Up to 28 weeks ]
- Number of Subjects With Adverse Events During the SC Treatment Period [ Time Frame: Up to 28 weeks ]
- Percentage of Subjects With Adverse Events During the SC Treatment Period [ Time Frame: Up to 28 weeks ]
- Time to Improvement During IgPro10 Re-stabilization Therapy [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Re-stabilization Therapy [ Time Frame: 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 IgPro10 Infusion During Re-stabilization Therapy [ Time Frame: Up to 13 weeks ]
- Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy [ Time Frame: Up to 13 weeks ]
- Percent of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy [ Time Frame: Up to 13 weeks ]
- Time to Improvement After CIDP Relapse During IgPro10 Rescue Therapy [ Time Frame: 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 [ Time Frame: Up to 13 weeks ]
- Number of Subjects With Adverse Events During IgPro10 Rescue Therapy [ Time Frame: Up to 13 weeks ]
- Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy [ Time Frame: Up to 13 weeks ]
- Change in Mean Grip Strength During IgPro10 Rescue Therapy [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01545076
Locations
Show 91 study locations
Sponsors and Collaborators
CSL Behring
ICON Clinical Research
Investigators
| Principal Investigator: | Prof. Dr. Ivo N. van Schaik | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | CSL Behring |
| ClinicalTrials.gov Identifier: | NCT01545076 |
| Other Study ID Numbers: |
IgPro20_3003 |
| First Posted: | March 6, 2012 Key Record Dates |
| Results First Posted: | July 5, 2018 |
| Last Update Posted: | July 5, 2018 |
| Last Verified: | December 2016 |
Additional relevant MeSH terms:
|
Polyneuropathies Polyradiculoneuropathy Polyradiculoneuropathy, Chronic Inflammatory Demyelinating Peripheral Nervous System Diseases Neuromuscular Diseases Nervous System Diseases Autoimmune Diseases of the Nervous System |
Demyelinating Diseases Autoimmune Diseases Immune System Diseases Immunoglobulins Antibodies Immunologic Factors Physiological Effects of Drugs |