Clinical trial NCT01545076: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyneuropathy
Polyradiculoneuropathy
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
Collaborators: name: ICON Clinical Research
First posted: 2012-03-06
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period
timeFrame: Up to 25 weeks
Secondary outcomes:
measure: Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period
timeFrame: Baseline and up to 25 weeks
measure: Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period
timeFrame: Baseline and up to 25 weeks
measure: Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period
timeFrame: Baseline and up to 25 weeks
measure: Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period
timeFrame: Baseline and up to 25 weeks
measure: Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period
timeFrame: Up to 25 weeks
measure: Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period
timeFrame: Up to 28 weeks
measure: Number of Subjects With Adverse Events During the SC Treatment Period
timeFrame: Up to 28 weeks
measure: Percentage of Subjects With Adverse Events During the SC Treatment Period
timeFrame: Up to 28 weeks
measure: Time to Improvement During IgPro10 Re-stabilization Therapy
timeFrame: Up to 13 weeks
measure: Change in Mean Grip Strength During IgPro10 Re-stabilization Therapy
timeFrame: Reference visit and up to 13 weeks
measure: Change in MRC Sum Score During IgPro10 Re-stabilization Therapy
timeFrame: Reference visit and up to 13 weeks
measure: Change in R-ODS During IgPro10 Re-stabilization Therapy
timeFrame: Reference visit and up to 13 weeks
measure: Change in INCAT During IgPro10 Re-stabilization Therapy
timeFrame: Reference visit and up to 13 weeks
measure: Number of Adverse Events Per IgPro10 Infusion During Re-stabilization Therapy
timeFrame: Up to 13 weeks
measure: Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy
timeFrame: Up to 13 weeks
measure: Percent of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy
timeFrame: Up to 13 weeks
measure: Time to Improvement After CIDP Relapse During IgPro10 Rescue Therapy
timeFrame: Up to 13 weeks
measure: Number of Adverse Events Per IgPro10 Infusion During Rescue Therapy
timeFrame: Up to 13 weeks
measure: Number of Subjects With Adverse Events During IgPro10 Rescue Therapy
timeFrame: Up to 13 weeks
measure: Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy
timeFrame: Up to 13 weeks
measure: Change in Mean Grip Strength During IgPro10 Rescue Therapy
timeFrame: Before first rescue IgPro10 infusion and up to 13 weeks
measure: Change in MRC Sum Score During IgPro10 Rescue Therapy
timeFrame: Before first rescue IgPro10 infusion and up to 13 weeks
measure: Change in R-ODS During IgPro10 Rescue Therapy
timeFrame: Before first rescue IgPro10 infusion and up to 13 weeks
measure: Change in INCAT During IgPro10 Rescue Therapy
timeFrame: Before first rescue IgPro10 infusion and up to 13 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site reference 8400181
state: Alabama
city: Phoenix
country: United States
facility: Site reference 8400173
state: Arizona
city: Phoenix
country: United States
facility: Site reference 8400172
state: Arizona
city: Los Angeles
country: United States
facility: Site reference 8400167
state: California
city: Centennial
country: United States
facility: Site reference 8400077
state: Colorado
city: Washington
country: United States
facility: Site Reference 8400352
state: District of Columbia
city: Miami
country: United States
facility: Site reference 8400214
state: Florida
city: Chicago
country: United States
facility: Site reference 8400162
state: Illinois
city: Chicago
country: United States
facility: Site Reference 8400247
state: Illinois
city: Indianapolis
country: United States
facility: Site Reference 8400215
state: Indiana
city: Kansas City
country: United States
facility: Site reference 8400166
state: Kansas
city: New Brunswick
country: United States
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state: New Jersey
city: New York
country: United States
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state: New York
city: New York
country: United States
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state: New York
city: Charlotte
country: United States
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state: North Carolina
city: Durham
country: United States
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state: North Carolina
city: Columbus
country: United States
facility: Site reference 8400178
state: Ohio
city: Oklahoma City
country: United States
facility: Site reference 8400217
state: Oklahoma
city: Nashville
country: United States
facility: Site Reference 8400177
state: Tennessee
city: Houston
country: United States
facility: Site reference 8400164
state: Texas
city: Charlottesville
country: United States
facility: Site Reference 8400268
state: Virginia
city: Seattle
country: United States
facility: Site Reference 8400340
state: Washington
city: Herston
country: Australia
facility: Site Reference 0360017
state: Queensland
city: Fitzroy
country: Australia
facility: Site reference 0360011
state: Victoria
city: Southport
country: Australia
facility: Site reference 0360008
city: Leuven
country: Belgium
facility: Site reference 0560003
city: Vancouver
country: Canada
facility: Site Reference 1240048
state: British Columbia
city: Montreal
country: Canada
facility: Site Reference 1240051
state: Quebec
city: Edmonton
country: Canada
facility: Site reference 1240006
city: Quebec
country: Canada
facility: Site reference 1240007
city: Toronto
country: Canada
facility: Site reference 1240009
city: Hradec Kralove
country: Czechia
facility: Site reference 2030002
city: Hradec Kralove
country: Czechia
facility: Site reference 2030009
city: Prague
country: Czechia
facility: Site reference 2030003
city: Tallinn
country: Estonia
facility: Site Reference 2330002
city: Tallinn
country: Estonia
facility: Site Reference 2330003
city: Helsinki
country: Finland
facility: Site reference 2460002
city: Clermont-Ferrand
country: France
facility: Site reference 2500024
city: Marseille
country: France
facility: Site reference 2500013
city: Nice
country: France
facility: Site reference 2500022
city: Pessac
country: France
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city: Berlin
country: Germany
facility: Site reference 2760048
city: Berlin
country: Germany
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city: Berlin
country: Germany
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city: Bochum
country: Germany
facility: Site reference 2760049
city: Duesseldorf
country: Germany
facility: Site reference 2760075
city: Essen
country: Germany
facility: Site Reference 2760094
city: Essen
country: Germany
facility: Site reference 2760052
city: Göttingen
country: Germany
facility: Site reference 2760036
city: Göttingen
country: Germany
facility: Site reference 2760053
city: Hannover
country: Germany
facility: Site reference 2760054
city: Ibbenbueren
country: Germany
facility: Site Reference 2760113
city: Koeln
country: Germany
facility: Site reference 2760080
city: Leipzig
country: Germany
facility: Site reference 2760055
city: Potsdam
country: Germany
facility: Site reference 2760047
city: Wuerzburg
country: Germany
facility: Site reference 2760039
city: Haifa
country: Israel
facility: Site reference 3760005
city: Tel Aviv
country: Israel
facility: Site reference 3760002
city: Chieti
country: Italy
facility: Site reference 3800026
city: Firenze
country: Italy
facility: Site reference 3800027
city: Genova
country: Italy
facility: Site reference 3800028
city: Milano
country: Italy
facility: Site reference 3800031
city: Roma
country: Italy
facility: Site reference 3800035
city: Roma
country: Italy
facility: Site reference 3800036
city: Rozzano
country: Italy
facility: Site reference 3800030
city: Torino
country: Italy
facility: Site reference 3800037
city: Aomori
country: Japan
facility: Site Reference 3920040
city: Aomori
country: Japan
facility: Site Reference 3920042
city: Chiba
country: Japan
facility: Site reference 3920038
city: Kanagawa
country: Japan
facility: Site reference 3920061
city: Matsumoto
country: Japan
facility: Site reference 3920045
city: Osaka
country: Japan
facility: Site reference 3920058
city: Saitama
country: Japan
facility: Site reference 3920037
city: Tokushima
country: Japan
facility: Site reference 3920034
city: Tokyo
country: Japan
facility: Site Reference 3920065
city: Tokyo
country: Japan
facility: Site Reference 3920062
city: Tokyo
country: Japan
facility: Site reference 3920032
city: Yamaguchi
country: Japan
facility: Site reference 3920035
city: Amsterdam
country: Netherlands
facility: Site reference 5280001
city: Maastricht
country: Netherlands
facility: Site reference 5280005
city: Utrecht
country: Netherlands
facility: Site reference 5280004
city: Gdansk
country: Poland
facility: Site Reference 6160058
city: Lodz
country: Poland
facility: Site Reference 6160060
city: Lublin
country: Poland
facility: Site Reference 6160055
city: Barcelona
country: Spain
facility: Site reference 7240010
city: Barcelona
country: Spain
facility: Site reference 7240011
city: Madrid
country: Spain
facility: Site reference 7240013
city: Madrid
country: Spain
facility: Site reference 7240014
city: Sevilla
country: Spain
facility: Site reference 7240016
city: London
country: United Kingdom
facility: Site reference 8260019
city: Manchester
country: United Kingdom
facility: Site Reference 8260032
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Prof. Dr. Ivo N. van Schaik
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Schaik IN, Bril V, van Geloven N, Hartung HP, Lewis RA, Sobue G, Lawo JP, Praus M, Mielke O, Durn BL, Cornblath DR, Merkies ISJ; PATH study group. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2018 Jan;17(1):35-46. doi: 10.1016/S1474-4422(17)30378-2. Epub 2017 Nov 6.
citation: van Schaik IN, van Geloven N, Bril V, Hartung HP, Lewis RA, Sobue G, Lawo JP, Mielke O, Cornblath DR, Merkies IS; PATH study group. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (The PATH Study): study protocol for a randomized controlled trial. Trials. 2016 Jul 25;17(1):345. doi: 10.1186/s13063-016-1466-2.