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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01545076




Registration number
NCT01545076
Ethics application status
Date submitted
1/03/2012
Date registered
6/03/2012
Date last updated
5/07/2018

Titles & IDs
Public title
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20)
Scientific 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
Secondary ID [1] 0 0
IgPro20_3003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Inflammatory Demyelinating Polyneuropathy 0 0
Polyradiculoneuropathy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Neurological 0 0 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - IgPro20 (low dose)
Treatment: Other - Placebo
Treatment: Other - IgPro10
Treatment: Other - IgPro20 (high dose)

Experimental: IgPro20 low dose -

Experimental: IgPro20 high dose -

Placebo comparator: Placebo -


Treatment: Other: 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)

Treatment: Other: Placebo
2% human albumin administered by weekly SC infusions during the SC treatment period of the study.

Treatment: Other: 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.

Treatment: Other: 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)
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period
Timepoint [1] 0 0
Up to 25 weeks
Secondary outcome [1] 0 0
Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period
Timepoint [1] 0 0
Baseline and up to 25 weeks
Secondary outcome [2] 0 0
Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period
Timepoint [2] 0 0
Baseline and up to 25 weeks
Secondary outcome [3] 0 0
Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period
Timepoint [3] 0 0
Baseline and up to 25 weeks
Secondary outcome [4] 0 0
Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period
Timepoint [4] 0 0
Baseline and up to 25 weeks
Secondary outcome [5] 0 0
Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period
Timepoint [5] 0 0
Up to 25 weeks
Secondary outcome [6] 0 0
Number of Adverse Events Per IgPro20 Infusion During the SC Treatment Period
Timepoint [6] 0 0
Up to 28 weeks
Secondary outcome [7] 0 0
Number of Subjects With Adverse Events During the SC Treatment Period
Timepoint [7] 0 0
Up to 28 weeks
Secondary outcome [8] 0 0
Percentage of Subjects With Adverse Events During the SC Treatment Period
Timepoint [8] 0 0
Up to 28 weeks
Secondary outcome [9] 0 0
Time to Improvement During IgPro10 Re-stabilization Therapy
Timepoint [9] 0 0
Up to 13 weeks
Secondary outcome [10] 0 0
Change in Mean Grip Strength During IgPro10 Re-stabilization Therapy
Timepoint [10] 0 0
Reference visit and up to 13 weeks
Secondary outcome [11] 0 0
Change in MRC Sum Score During IgPro10 Re-stabilization Therapy
Timepoint [11] 0 0
Reference visit and up to 13 weeks
Secondary outcome [12] 0 0
Change in R-ODS During IgPro10 Re-stabilization Therapy
Timepoint [12] 0 0
Reference visit and up to 13 weeks
Secondary outcome [13] 0 0
Change in INCAT During IgPro10 Re-stabilization Therapy
Timepoint [13] 0 0
Reference visit and up to 13 weeks
Secondary outcome [14] 0 0
Number of Adverse Events Per IgPro10 Infusion During Re-stabilization Therapy
Timepoint [14] 0 0
Up to 13 weeks
Secondary outcome [15] 0 0
Number of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy
Timepoint [15] 0 0
Up to 13 weeks
Secondary outcome [16] 0 0
Percent of Subjects With Adverse Events During IgPro10 Re-stabilization Therapy
Timepoint [16] 0 0
Up to 13 weeks
Secondary outcome [17] 0 0
Time to Improvement After CIDP Relapse During IgPro10 Rescue Therapy
Timepoint [17] 0 0
Up to 13 weeks
Secondary outcome [18] 0 0
Number of Adverse Events Per IgPro10 Infusion During Rescue Therapy
Timepoint [18] 0 0
Up to 13 weeks
Secondary outcome [19] 0 0
Number of Subjects With Adverse Events During IgPro10 Rescue Therapy
Timepoint [19] 0 0
Up to 13 weeks
Secondary outcome [20] 0 0
Percent of Subjects With Adverse Events During IgPro10 Rescue Therapy
Timepoint [20] 0 0
Up to 13 weeks
Secondary outcome [21] 0 0
Change in Mean Grip Strength During IgPro10 Rescue Therapy
Timepoint [21] 0 0
Before first rescue IgPro10 infusion and up to 13 weeks
Secondary outcome [22] 0 0
Change in MRC Sum Score During IgPro10 Rescue Therapy
Timepoint [22] 0 0
Before first rescue IgPro10 infusion and up to 13 weeks
Secondary outcome [23] 0 0
Change in R-ODS During IgPro10 Rescue Therapy
Timepoint [23] 0 0
Before first rescue IgPro10 infusion and up to 13 weeks
Secondary outcome [24] 0 0
Change in INCAT During IgPro10 Rescue Therapy
Timepoint [24] 0 0
Before first rescue IgPro10 infusion and up to 13 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2016
Sample size
Target
Accrual to date
Final
208
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Site Reference 0360017 - Herston
Recruitment hospital [2] 0 0
Site reference 0360011 - Fitzroy
Recruitment hospital [3] 0 0
Site reference 0360008 - Southport
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
- Fitzroy
Recruitment postcode(s) [3] 0 0
- Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
Canada
State/province [20] 0 0
British Columbia
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Canada
State/province [22] 0 0
Edmonton
Country [23] 0 0
Canada
State/province [23] 0 0
Toronto
Country [24] 0 0
Czechia
State/province [24] 0 0
Hradec Kralove
Country [25] 0 0
Czechia
State/province [25] 0 0
Prague
Country [26] 0 0
Estonia
State/province [26] 0 0
Tallinn
Country [27] 0 0
Finland
State/province [27] 0 0
Helsinki
Country [28] 0 0
France
State/province [28] 0 0
Clermont-Ferrand
Country [29] 0 0
France
State/province [29] 0 0
Marseille
Country [30] 0 0
France
State/province [30] 0 0
Nice
Country [31] 0 0
France
State/province [31] 0 0
Pessac
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Bochum
Country [34] 0 0
Germany
State/province [34] 0 0
Duesseldorf
Country [35] 0 0
Germany
State/province [35] 0 0
Essen
Country [36] 0 0
Germany
State/province [36] 0 0
Göttingen
Country [37] 0 0
Germany
State/province [37] 0 0
Hannover
Country [38] 0 0
Germany
State/province [38] 0 0
Ibbenbueren
Country [39] 0 0
Germany
State/province [39] 0 0
Koeln
Country [40] 0 0
Germany
State/province [40] 0 0
Leipzig
Country [41] 0 0
Germany
State/province [41] 0 0
Potsdam
Country [42] 0 0
Germany
State/province [42] 0 0
Wuerzburg
Country [43] 0 0
Israel
State/province [43] 0 0
Haifa
Country [44] 0 0
Israel
State/province [44] 0 0
Tel Aviv
Country [45] 0 0
Italy
State/province [45] 0 0
Chieti
Country [46] 0 0
Italy
State/province [46] 0 0
Firenze
Country [47] 0 0
Italy
State/province [47] 0 0
Genova
Country [48] 0 0
Italy
State/province [48] 0 0
Milano
Country [49] 0 0
Italy
State/province [49] 0 0
Roma
Country [50] 0 0
Italy
State/province [50] 0 0
Rozzano
Country [51] 0 0
Italy
State/province [51] 0 0
Torino
Country [52] 0 0
Japan
State/province [52] 0 0
Aomori
Country [53] 0 0
Japan
State/province [53] 0 0
Chiba
Country [54] 0 0
Japan
State/province [54] 0 0
Kanagawa
Country [55] 0 0
Japan
State/province [55] 0 0
Matsumoto
Country [56] 0 0
Japan
State/province [56] 0 0
Osaka
Country [57] 0 0
Japan
State/province [57] 0 0
Saitama
Country [58] 0 0
Japan
State/province [58] 0 0
Tokushima
Country [59] 0 0
Japan
State/province [59] 0 0
Tokyo
Country [60] 0 0
Japan
State/province [60] 0 0
Yamaguchi
Country [61] 0 0
Netherlands
State/province [61] 0 0
Amsterdam
Country [62] 0 0
Netherlands
State/province [62] 0 0
Maastricht
Country [63] 0 0
Netherlands
State/province [63] 0 0
Utrecht
Country [64] 0 0
Poland
State/province [64] 0 0
Gdansk
Country [65] 0 0
Poland
State/province [65] 0 0
Lodz
Country [66] 0 0
Poland
State/province [66] 0 0
Lublin
Country [67] 0 0
Spain
State/province [67] 0 0
Barcelona
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Spain
State/province [69] 0 0
Sevilla
Country [70] 0 0
United Kingdom
State/province [70] 0 0
London
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CSL Behring
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ICON Clinical Research
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01545076
Trial related presentations / publications
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. Erratum In: Lancet Neurol. 2018 Jan;17(1):26. doi: 10.1016/S1474-4422(17)30427-1. Lancet Neurol. 2018 Aug;17(8):661. doi: 10.1016/S1474-4422(18)30260-6.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Prof. Dr. Ivo N. van Schaik
Address 0 0
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01545076