Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20)

Chronic Inflammatory Demyelinating Polyneuropathy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01545076
• Other study ID #: IgPro20_3003
• Status: Completed
• Phase: Phase 3
• Start date: March 2012
• Est. completion date: September 2016

Study information

• Verified date: December 2016
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Inflammatory Demyelinating Polyneuropathy
• Polyneuropathies
• Polyradiculoneuropathy
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention

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)
• Placebo
2% human albumin administered by weekly SC infusions during the SC treatment period of the study.
• 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.
• 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)

Locations

Country	Name	City	State
Australia	Site reference 0360011	Fitzroy	Victoria
Australia	Site Reference 0360017	Herston	Queensland
Australia	Site reference 0360008	Southport
Belgium	Site reference 0560003	Leuven
Canada	Site reference 1240006	Edmonton
Canada	Site Reference 1240051	Montreal	Quebec
Canada	Site reference 1240007	Quebec
Canada	Site reference 1240009	Toronto
Canada	Site Reference 1240048	Vancouver	British Columbia
Czechia	Site reference 2030002	Hradec Kralove
Czechia	Site reference 2030009	Hradec Kralove
Czechia	Site reference 2030003	Prague
Estonia	Site Reference 2330002	Tallinn
Estonia	Site Reference 2330003	Tallinn
Finland	Site reference 2460002	Helsinki
France	Site reference 2500024	Clermont-Ferrand
France	Site reference 2500013	Marseille
France	Site reference 2500022	Nice
France	Site reference 2500019	Pessac
Germany	Site reference 2760048	Berlin
Germany	Site reference 2760069	Berlin
Germany	Site reference 2760072	Berlin
Germany	Site reference 2760049	Bochum
Germany	Site reference 2760075	Duesseldorf
Germany	Site reference 2760052	Essen
Germany	Site Reference 2760094	Essen
Germany	Site reference 2760036	Göttingen
Germany	Site reference 2760053	Göttingen
Germany	Site reference 2760054	Hannover
Germany	Site Reference 2760113	Ibbenbueren
Germany	Site reference 2760080	Koeln
Germany	Site reference 2760055	Leipzig
Germany	Site reference 2760047	Potsdam
Germany	Site reference 2760039	Wuerzburg
Israel	Site reference 3760005	Haifa
Israel	Site reference 3760002	Tel Aviv
Italy	Site reference 3800026	Chieti
Italy	Site reference 3800027	Firenze
Italy	Site reference 3800028	Genova
Italy	Site reference 3800031	Milano
Italy	Site reference 3800035	Roma
Italy	Site reference 3800036	Roma
Italy	Site reference 3800030	Rozzano
Italy	Site reference 3800037	Torino
Japan	Site Reference 3920040	Aomori
Japan	Site Reference 3920042	Aomori
Japan	Site reference 3920038	Chiba
Japan	Site reference 3920061	Kanagawa
Japan	Site reference 3920045	Matsumoto
Japan	Site reference 3920058	Osaka
Japan	Site reference 3920037	Saitama
Japan	Site reference 3920034	Tokushima
Japan	Site reference 3920032	Tokyo
Japan	Site Reference 3920062	Tokyo
Japan	Site Reference 3920065	Tokyo
Japan	Site reference 3920035	Yamaguchi
Netherlands	Site reference 5280001	Amsterdam
Netherlands	Site reference 5280005	Maastricht
Netherlands	Site reference 5280004	Utrecht
Poland	Site Reference 6160058	Gdansk
Poland	Site Reference 6160060	Lodz
Poland	Site Reference 6160055	Lublin
Spain	Site reference 7240010	Barcelona
Spain	Site reference 7240011	Barcelona
Spain	Site reference 7240013	Madrid
Spain	Site reference 7240014	Madrid
Spain	Site reference 7240016	Sevilla
United Kingdom	Site reference 8260019	London
United Kingdom	Site Reference 8260032	Manchester
United States	Site reference 8400181	Birmingham	Alabama
United States	Site reference 8400077	Centennial	Colorado
United States	Site reference 8400182	Charlotte	North Carolina
United States	Site Reference 8400268	Charlottesville	Virginia
United States	Site reference 8400162	Chicago	Illinois
United States	Site Reference 8400247	Chicago	Illinois
United States	Site reference 8400178	Columbus	Ohio
United States	Site Reference 8400346	Durham	North Carolina
United States	Site reference 8400164	Houston	Texas
United States	Site Reference 8400215	Indianapolis	Indiana
United States	Site reference 8400166	Kansas City	Kansas
United States	Site reference 8400167	Los Angeles	California
United States	Site reference 8400214	Miami	Florida
United States	Site Reference 8400177	Nashville	Tennessee
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 8400217	Oklahoma City	Oklahoma
United States	Site reference 8400172	Phoenix	Arizona
United States	Site reference 8400173	Phoenix	Arizona
United States	Site Reference 8400340	Seattle	Washington
United States	Site Reference 8400352	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
CSL Behring	ICON Clinical Research

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Estonia,  Finland,  France,  Germany,  Israel,  Italy,  Japan,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 25 weeks
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.	Baseline and up to 25 weeks
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.	Baseline and up to 25 weeks
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).	Baseline and up to 25 weeks
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).	Baseline and up to 25 weeks
Secondary	Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period		Up to 25 weeks
Secondary	Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period		Up to 28 weeks
Secondary	Number of Subjects With Adverse Events During the SC Treatment Period		Up to 28 weeks
Secondary	Percentage of Subjects With Adverse Events During the SC Treatment Period		Up to 28 weeks
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.	Up to 13 weeks
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.	Reference visit and up to 13 weeks
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).	Reference visit and up to 13 weeks
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).	Reference visit and up to 13 weeks
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.	Reference visit and up to 13 weeks
Secondary	Number of Adverse Events Per IgPro10 Infusion During Re-stabilization Therapy		Up to 13 weeks
Secondary	Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy		Up to 13 weeks
Secondary	Percent of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy		Up to 13 weeks
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.	Up to 13 weeks
Secondary	Number of Adverse Events Per IgPro10 Infusion During Rescue Therapy		Up to 13 weeks
Secondary	Number of Subjects With Adverse Events During IgPro10 Rescue Therapy		Up to 13 weeks
Secondary	Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy		Up to 13 weeks
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.	Before first rescue IgPro10 infusion and up to 13 weeks
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).	Before first rescue IgPro10 infusion and up to 13 weeks
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).	Before first rescue IgPro10 infusion and up to 13 weeks
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.	Before first rescue IgPro10 infusion and up to 13 weeks