Extension Study of Maintenance Treatment With Subcutaneous Immunoglobulin (IgPro20) for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Multicenter, Open-label Extension Study to Investigate the Long-term Safety and Efficacy of IgPro20 in Maintenance Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Subjects Completing Study IgPro20_3003

This study is an extension study to the pivotal study IgPro20_3003 (NCT01545076). The purpose of this extension study is to investigate the long-term treatment of CIDP with IgPro20, with regard to safety and efficacy.

Subjects who have completed subcutaneous (SC) Week 25 or were successfully rescued from a CIDP relapse during the SC Treatment Period of pivotal study IgPro20_3003 (NCT01545076) will have the option to receive open-label low-dose IgPro20 (0.2 g/kg bodyweight [bw]) weekly for up to 48 weeks. Subjects relapsing on low-dose IgPro20 will either return to high-dose IgPro20 (0.4 g/kg) immediately or be discontinued, depending on investigator's judgment. Subjects returning to high-dose IgPro20 will continue on high-dose until they have completed a total of 48 weeks of IgPro20 treatment. If subjects do not successfully recover from CIDP relapse within 4 weeks, they will be withdrawn.

The treatment duration will be up to 48 weeks, followed by a completion visit (week 49).

Study Overview

• Status: Completed
• Conditions: Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
• Intervention / Treatment: Biological: IgPro20

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Site Reference 0360017
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Site Reference 0360011
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Site Reference 1240009
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V2J2
      • Site Reference 1240007
• Czechia
  • Hradec Kralove, Czechia, 50003
    • Site Reference 2030009
  • Hradec Kralove, Czechia, 50005
    • Site Reference 2030002
• France
  • Nice Cedex 1, France, 06002
    • Site Reference 2500022
• Germany
  • Berlin, Germany, 10117
    • Site Reference 2760069
  • Berlin, Germany, 12200
    • Site Reference 2760072
  • Bochum, Germany, 44791
    • Site Reference 2760049
  • Essen, Germany, 45147
    • Site Reference 2760094
  • Hannover, Germany, 30625
    • Site Reference 2760054
  • Leipzig, Germany, DE04103
    • Site Reference 2760055
  • Potsdam, Germany, 14471
    • Site Reference 2760047
  • Wurzburg, Germany, 97080
    • Site Reference 2760039
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45117
      • Site Reference 2760052
• Italy
  • Milano, Italy, 20133
    • Site Reference 3800031
• Japan
  • Chiba, Japan, 260-8677
    • Site Reference 3920038
  • Kanagawa, Japan, 228-8555
    • Site Reference 3920061
  • Nagoya, Japan, 466-8560
    • Site Reference 3920040
  • Tokyo, Japan, 113-8431
    • Site Reference 3920065
  • Saitama
    • Tokorozawa, Saitama, Japan, 359-8513
      • Site Reference 3920037
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505
      • Site Reference 3920035
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Site Reference 5280001
• Spain
  • Barcelona, Spain, 08035
    • Site Reference 7240011
  • Barcelona, Spain, 08907
    • Site Reference 7240010
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • Site Reference 8260019
  • Salford, United Kingdom, M6 8HD
    • Site Reference 8260032
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0017
      • Site Reference 8400181
  • California
    • Los Angeles, California, United States, 90033
      • Site Reference 8400167
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Site Reference 8400166
  • New York
    • New York, New York, United States, 10021
      • Site Reference 8400169
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Site Reference 8400182

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects having completed the pivotal study IgPro20_3003 (SC Week 25) or successfully rescued from a CIDP relapse during the SC Treatment Period of pivotal study IgPro20_3003 (NCT01545076).
• Written informed consent for study participation obtained before undergoing any study-specific procedures.

Exclusion Criteria:

• Subject is unable to directly transition from study IgPro20_3003.
• New medical condition and/or social behavior (ie, alcohol, drug, or medication abuse) during participation in study IgPro20_3003 that in the judgment of the investigator could increase risk to the subject, interfere with the evaluation of investigational medicinal product, and/or conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IgPro20; 20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg bw (low-dose IgPro20) for up to 48 weeks. Subjects who experience CIDP relapse on 0.2 g/kg IgPro20 will have an increase to 0.4 g/kg IgPro20 immediately and will continue on high-dose until they have completed a total of 48 weeks of IgPro20 treatment.	Biological: IgPro20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Adverse Events (AEs) Per Infusion	Up to 49 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First CIDP Relapse	Time to first CIDP relapse based on adjusted INCAT score, using the Kaplan-Meier estimator. 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 only).	Up to 49 weeks
Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) 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.	Baseline and up to 49 weeks
Change From Baseline in Medical Research Council (MRC) Score	An adapted version of the MRC sum score as published by Kleyweg and the RMC trial group was used. With the MRC sum score, the following 8 bilateral muscle pairs were assessed, and individual muscle scores as well as the sum score documented: Shoulder abduction; Elbow flexion; Wrist extension; Index finger abduction; Hip flexion; Knee extension; Foot dorsiflexion; Great toe dorsiflexion. The MRC sum score ranges from 0 (paralysis) to 80 (normal strength) points.	Baseline and up to 49 weeks
Change From Baseline in Rasch-built Overall Disability Scale (R-ODS)	The R-ODS is a recently published outcome measure that captures activity and social participation in subjects with Guillain-Barré Syndrome, CIDP, and monoclonal gammopathy of uncertain significance. The 24-item questionnaire covers a wide range of tasks of daily life that are each to be rated as "impossible to perform", "able to perform with difficulty", or "easy to perform" (scale of 0 - 2 points respectively). Items are sorted in order of increasing difficulty to perform, based on data from subjects with peripheral neuropathies (chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome, or monoclonal gammopathy of uncertain significance) and subjects recruited at the university outpatient clinics of Rotterdam and Maastricht.	Baseline and up to 49 weeks
Change From Baseline in Mean Grip Strength	The hand-held Vigorimeter from Martin (Tuttlingen, Germany) is a device that measures the strength of small muscles in the hand, ie, grip strength. The subject squeezes a rubber bulb lying between the palm of the hand and the thumb and index fingers. The pressure is recorded via a rubber tube on a nanometer and expressed in kilopascal (kPa). At each assessment, the subject squeezes 3 times with each hand.	Baseline and up to 49 weeks
Percentage of Subjects With Adverse Events (AEs)		Up to 49 weeks
Number of AEs by Severity Per Infusion		Up to 49 weeks
Percentage of Subjects With AEs by Severity		Up to 49 weeks
Number of Causally Related AEs Per Infusion		Up to 49 weeks
Percentage of Subjects With Causally Related AEs		Up to 49 weeks
Number of Serious AEs Per Infusion		Up to 49 weeks
Percentage of Subjects With Serious AEs		Up to 49 weeks

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Principal Investigator: Prof. Dr. Ivo N. van Schaik, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2014
• Primary Completion (Actual): July 10, 2017
• Study Completion (Actual): July 10, 2017

Study Registration Dates

• First Submitted: January 3, 2014
• First Submitted That Met QC Criteria: January 3, 2014
• First Posted (Estimate): January 6, 2014

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyneuropathies; Polyradiculoneuropathy; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
• Other Study ID Numbers: IgPro20_3004; 2013-004157-24 (EudraCT Number)