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

Study Overview
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Brief Summary
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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 If subjects do not successfully recover from CIDP relapse within 4 weeks, they will be withdrawn.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).

Official Title
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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

Conditions
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Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention / Treatment
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* Biological: IgPro20


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IgPro20<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |