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

• ClinicalTrials.gov Identifier: NCT02027701
• Recruitment Status: Completed
• First Posted: January 6, 2014
• Results First Posted: October 2, 2018
• Last Update Posted: October 2, 2018
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: January 3, 2014
• First Posted Date: January 6, 2014
• Results First Submitted Date: July 9, 2018
• Results First Posted Date: October 2, 2018
• Last Update Posted Date: October 2, 2018
• Actual Study Start Date: July 30, 2014
• Actual Primary Completion Date: July 10, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 6, 2018): Number of Adverse Events (AEs) Per Infusion [ Time Frame: Up to 49 weeks ]

Original Primary Outcome Measures (submitted: January 3, 2014)

Overall rate of adverse events (AEs) per infusion - high-dose IgPro20 [ Time Frame: Up to 48 weeks ]

Overall rate of AEs per infusion during high-dose IgPro20 treatment

Current Secondary Outcome Measures (submitted: September 6, 2018)

• Time to First CIDP Relapse [ Time Frame: Up to 49 weeks ]
  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).
• Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Score [ Time Frame: Baseline and up to 49 weeks ]
  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.
• Change From Baseline in Medical Research Council (MRC) Score [ Time Frame: Baseline and up to 49 weeks ]
  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.
• Change From Baseline in Rasch-built Overall Disability Scale (R-ODS) [ Time Frame: Baseline and up to 49 weeks ]
  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.
• Change From Baseline in Mean Grip Strength [ Time Frame: Baseline and up to 49 weeks ]
  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.
• Percentage of Subjects With Adverse Events (AEs) [ Time Frame: Up to 49 weeks ]
• Number of AEs by Severity Per Infusion [ Time Frame: Up to 49 weeks ]
• Percentage of Subjects With AEs by Severity [ Time Frame: Up to 49 weeks ]
• Number of Causally Related AEs Per Infusion [ Time Frame: Up to 49 weeks ]
• Percentage of Subjects With Causally Related AEs [ Time Frame: Up to 49 weeks ]
• Number of Serious AEs Per Infusion [ Time Frame: Up to 49 weeks ]
• Percentage of Subjects With Serious AEs [ Time Frame: Up to 49 weeks ]

Original Secondary Outcome Measures (submitted: January 3, 2014)

• Rate of adverse events (AEs) per infusion by severity, causality, and seriousness - high-dose IgPro20 [ Time Frame: Up to 48 weeks ]
• Percentage of subjects with adverse events (AEs) - high-dose IgPro20 [ Time Frame: Up to 48 weeks ]
  Percentage of subjects with AEs, overall and by severity, causality and seriousness, during high-dose IgPro20 treatment.
• Rate of adverse events (AEs) per infusion - low-dose IgPro20 [ Time Frame: Up to 28 weeks ]
  Rate of AEs per infusion, overall and by severity, causality and seriousness, during low-dose IgPro20 treatment
• Percentage of subjects with adverse events (AEs) - low-dose IgPro20 [ Time Frame: Up to 28 weeks ]
  Percentage of subjects with AEs, overall and by severity, causality and seriousness, during low-dose IgPro20 treatment
• Total Inflammatory Neuropathy Cause and Treatment (INCAT) score at all study visits [ Time Frame: Up to 49 weeks (baseline [Week 1], Weeks 2, 9, 17, 25, 33, 41, and at completion visit) ]
• Time to first CIDP relapse [ Time Frame: Up to 49 weeks ]
  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).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Extension Study of Maintenance Treatment With Subcutaneous Immunoglobulin (IgPro20) for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
• Official Title: 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

Brief Summary

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).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

• Intervention: Biological: IgPro20

Study Arms

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.

Intervention: Biological: IgPro20

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 10, 2016): 82
• Original Estimated Enrollment (submitted: January 3, 2014): 70
• Actual Study Completion Date: July 10, 2017
• Actual Primary Completion Date: July 10, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czechia, France, Germany, Italy, Japan, Netherlands, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic, Finland

Administrative Information

• NCT Number: NCT02027701
• Other Study ID Numbers: IgPro20_3004; 2013-004157-24 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: CSL Behring
• Original Responsible Party: Same as current
• Current Study Sponsor: CSL Behring
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Prof. Dr. Ivo N. van Schaik; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

• PRS Account: CSL Behring
• Verification Date: September 2018