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

• Sponsor: CSL Behring (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02027701
• Collaborator: (none)
• Enrollment: 82
• Locations: 33
• Arm: 1
• Actual Duration (Months): 35.4
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 If subjects do not successfully recover from CIDP relapse within 4 weeks, they will be withdrawn.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

Condition or Disease	Intervention/Treatment	Phase
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP); Polyradiculoneuropathy, Chronic Inflammatory Demyelinating	Biological: IgPro20	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jul 30, 2014
• Actual Primary Completion Date: Jul 10, 2017
• Actual Study Completion Date: Jul 10, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events (AEs) Per Infusion [Up to 49 weeks]

Secondary Outcome Measures

1. Time to First CIDP Relapse [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).

2. Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Score [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.

3. Change From Baseline in Medical Research Council (MRC) Score [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.

4. Change From Baseline in Rasch-built Overall Disability Scale (R-ODS) [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.

5. Change From Baseline in Mean Grip Strength [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.

6. Percentage of Subjects With Adverse Events (AEs) [Up to 49 weeks]

7. Number of AEs by Severity Per Infusion [Up to 49 weeks]

8. Percentage of Subjects With AEs by Severity [Up to 49 weeks]

9. Number of Causally Related AEs Per Infusion [Up to 49 weeks]

10. Percentage of Subjects With Causally Related AEs [Up to 49 weeks]

11. Number of Serious AEs Per Infusion [Up to 49 weeks]

12. Percentage of Subjects With Serious AEs [Up to 49 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• CSL Behring

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Dec 8, 2015
• Statistical Analysis Plan - Feb 24, 2017

More Information

Publications

None provided.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT02027701
• Other Study ID Numbers: IgPro20_3004; 2013-004157-24
• First Posted: Jan 6, 2014
• Last Update Posted: Oct 2, 2018
• Last Verified: Sep 1, 2018

• Additional relevant MeSH terms: Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Polyradiculoneuropathy

Study Results

Participant Flow

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin administered SC weekly at 0.2 g/kg, and subjects who experience CIDP relapse on 0.2 g/kg IgPro20 will have an increase to 0.4 g/kg IgPro20.
Period Title: Overall Study
STARTED	82
COMPLETED	66
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly at 0.2 g/kg or 0.4 g/kg.
Overall Participants	82
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	55 67.1%
>=65 years	27 32.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.57 (13.224)
Sex: Female, Male (Count of Participants)
Female	32 39%
Male	50 61%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 17.1%
Not Hispanic or Latino	66 80.5%
Unknown or Not Reported	2 2.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.2%
Asian	10 12.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	70 85.4%
More than one race	0 0%
Unknown or Not Reported	1 1.2%
Region of Enrollment (participants) [Number]
Canada	7 8.5%
Netherlands	1 1.2%
United States	9 11%
Czechia	2 2.4%
Japan	10 12.2%
Italy	8 9.8%
United Kingdom	4 4.9%
Australia	1 1.2%
France	1 1.2%
Germany	29 35.4%
Spain	10 12.2%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety Data Set (SDS): all subjects who received at least 1 dose of IgPro20 in this study.

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Measure Infusions	5553
Number [Adverse events per infusion]	0.032

2. Secondary Outcome

Title	Time to First CIDP Relapse
Description	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).
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

Total Set: all subjects enrolled in the study, ie, the subject's informed consent was obtained. In the study protocol, this analysis set was referred to as the Intention-to-Treat Data Set.

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Median (95% Confidence Interval) [Days]	266.0

3. Secondary Outcome

Title	Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Score
Description	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.
Time Frame	Baseline and up to 49 weeks

Outcome Measure Data

Analysis Population Description

Total Set

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	80
Median (Full Range) [units on a scale]	0.0

4. Secondary Outcome

Title	Change From Baseline in Medical Research Council (MRC) Score
Description	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.
Time Frame	Baseline and up to 49 weeks

Outcome Measure Data

Analysis Population Description

Total Set

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	78
Median (Full Range) [units on a scale]	0.0

5. Secondary Outcome

Title	Change From Baseline in Rasch-built Overall Disability Scale (R-ODS)
Description	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.
Time Frame	Baseline and up to 49 weeks

Outcome Measure Data

Analysis Population Description

Total Set

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	71
Median (Full Range) [units on a scale]	0.0

6. Secondary Outcome

Title	Change From Baseline in Mean Grip Strength
Description	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.
Time Frame	Baseline and up to 49 weeks

Outcome Measure Data

Analysis Population Description

Total Set

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	79
Median (Full Range) [kPa]	-0.7

7. Secondary Outcome

Title	Percentage of Subjects With Adverse Events (AEs)
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

SDS

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Number [percentage of subjects]	75.6

8. Secondary Outcome

Title	Number of AEs by Severity Per Infusion
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

SDS

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Measure Infusions	5553
Mild	0.024
Moderate	0.006
Severe	0.002

9. Secondary Outcome

Title	Percentage of Subjects With AEs by Severity
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

SDS

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly at 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Mild	62.2
Moderate	29.3
Severe	9.8

10. Secondary Outcome

Title	Number of Causally Related AEs Per Infusion
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

SDS

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly: 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Measure Infusions	5553
Number [Adverse events per infusion]	0.011

11. Secondary Outcome

Title	Percentage of Subjects With Causally Related AEs
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

SDS

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly at 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Number [percentage of subjects]	25.6

12. Secondary Outcome

Title	Number of Serious AEs Per Infusion
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

SDS

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly at 0.2 g/kg for up to 49 weeks.
Measure Participants	82
Measure Infusions	5553
Number [Adverse events per infusion]	0.001

13. Secondary Outcome

Title	Percentage of Subjects With Serious AEs
Time Frame	Up to 49 weeks

Outcome Measure Data

Analysis Population Description

SDS

Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly at 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
Measure Participants	82
Number [percentage of subjects]	8.5

Adverse Events

Time Frame	Up to 49 weeks
Arm/Group Title	IgPro20
Arm/Group Description	20% liquid formulation (200 mg/mL) of human normal immunoglobulin for SC use administered SC weekly at 0.2 g/kg or 0.4 g/kg for up to 49 weeks.
All Cause Mortality
	IgPro20
	Affected / at Risk (%)	# Events
Total	0/82 (0%)
Serious Adverse Events
	IgPro20
	Affected / at Risk (%)	# Events
Total	7/82 (8.5%)
Cardiac disorders
Atrial Flutter	2/82 (2.4%)	2
Gastrointestinal disorders
Faecaloma	1/82 (1.2%)	1
Hepatobiliary disorders
Gallbladder Perforation	1/82 (1.2%)	1
Immune system disorders
Chronic Inflammatory Demyelinating Polyradiculoneuropathy	1/82 (1.2%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/82 (1.2%)	1
Nervous system disorders
Nerve Compression	1/82 (1.2%)	1
Renal and urinary disorders
Urinary Tract Infection	1/82 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Sepsis	1/82 (1.2%)	1
Other (Not Including Serious) Adverse Events
	IgPro20
	Affected / at Risk (%)	# Events
Total	25/82 (30.5%)
Infections and infestations
Nasopharyngitis	11/82 (13.4%)	13
Nervous system disorders
Headache	4/82 (4.9%)	5
Skin and subcutaneous tissue disorders
Infusion site swelling	9/82 (11%)	11
Infusion site erythema	7/82 (8.5%)	9
Infusion site swelling	9/82 (11%)	11
Infusion Site erythema	7/82 (8.5%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

CSL agreements may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and requests that reports based on single-site data not precede the primary publication of the entire clinical trial.