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

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP); Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
• Intervention: Biological: IgPro20
• Enrollment: 82

Participant Flow

Recruitment Details
Pre-assignment Details

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
Reason Not Completed
Adverse Event	3
Lack of Efficacy	8
Physician Decision	2
Withdrawal by Subject	3

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 Number of Baseline Participants		82
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	55 67.1%
	>=65 years	27 32.9%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	82 participants
		57.57 (13.224)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants
	Female	32 39.0%
	Male	50 61.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants
	Hispanic or Latino	14 17.1%
	Not Hispanic or Latino	66 80.5%
	Unknown or Not Reported	2 2.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants
	American Indian or Alaska Native	1 1.2%
	Asian	10 12.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	70 85.4%
	More than one race	0 0.0%
	Unknown or Not Reported	1 1.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	82 participants
Canada		7
Netherlands		1
United States		9
Czechia		2
Japan		10
Italy		8
United Kingdom		4
Australia		1
France		1
Germany		29
Spain		10

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events (AEs) Per Infusion
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Overall Number of Units Analyzed; Type of Units Analyzed: Infusions	5553
Measure Type: Number; Unit of Measure: 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.
Overall Number of Participants Analyzed	82
Median (95% Confidence Interval); Unit of Measure: Days
	266.0 [1]; (225.0 to NA)

[1]

The upper limit of the 95% confidence interval for the median time to relapse cannot be estimated, because the curve representing the upper confidence limit lies above 0.5.

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.
Overall Number of Participants Analyzed	80
Median (Full Range); Unit of Measure: units on a scale
	0.0; (-3 to 6)

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.
Overall Number of Participants Analyzed	78
Median (Full Range); Unit of Measure: units on a scale
	0.0; (-23 to 18)

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.
Overall Number of Participants Analyzed	71
Median (Full Range); Unit of Measure: units on a scale
	0.0; (-76 to 33)

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.
Overall Number of Participants Analyzed	79
Median (Full Range); Unit of Measure: kPa
	-0.7; (-80 to 27)

7. Secondary Outcome

Title	Percentage of Subjects With Adverse Events (AEs)
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Measure Type: Number; Unit of Measure: percentage of subjects
	75.6

8. Secondary Outcome

Title	Number of AEs by Severity Per Infusion
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Overall Number of Units Analyzed; Type of Units Analyzed: Infusions	5553
Measure Type: Number; Unit of Measure: Adverse events per infusion
Mild	0.024
Moderate	0.006
Severe	0.002

9. Secondary Outcome

Title	Percentage of Subjects With AEs by Severity
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Measure Type: Number; Unit of Measure: percentage of subjects
Mild	62.2
Moderate	29.3
Severe	9.8

10. Secondary Outcome

Title	Number of Causally Related AEs Per Infusion
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Overall Number of Units Analyzed; Type of Units Analyzed: Infusions	5553
Measure Type: Number; Unit of Measure: Adverse events per infusion
	0.011

11. Secondary Outcome

Title	Percentage of Subjects With Causally Related AEs
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Measure Type: Number; Unit of Measure: percentage of subjects
	25.6

12. Secondary Outcome

Title	Number of Serious AEs Per Infusion
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Overall Number of Units Analyzed; Type of Units Analyzed: Infusions	5553
Measure Type: Number; Unit of Measure: Adverse events per infusion
	0.001

13. Secondary Outcome

Title	Percentage of Subjects With Serious AEs
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	82
Measure Type: Number; Unit of Measure: percentage of subjects
	8.5

Adverse Events

Time Frame	Up to 49 weeks
Adverse Event Reporting Description	[Not Specified]
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 (%)
Total	0/82 (0.00%)
Serious Adverse Events
	IgPro20
	Affected / at Risk (%)	# Events
Total	7/82 (8.54%)
Cardiac disorders
Atrial Flutter † 1	2/82 (2.44%)	2
Gastrointestinal disorders
Faecaloma † 1	1/82 (1.22%)	1
Hepatobiliary disorders
Gallbladder Perforation † 1	1/82 (1.22%)	1
Immune system disorders
Chronic Inflammatory Demyelinating Polyradiculoneuropathy † 1	1/82 (1.22%)	1
Musculoskeletal and connective tissue disorders
Back Pain † 1 [1]	1/82 (1.22%)	1
Nervous system disorders
Nerve Compression † 1	1/82 (1.22%)	1
Renal and urinary disorders
Urinary Tract Infection † 1	1/82 (1.22%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Sepsis † 1	1/82 (1.22%)	1
1 Term from vocabulary, MedDRA (14.1); † Indicates events were collected by systematic assessment; [1] Worsening of upper back pain secondary to fall. Non-treatment emergent SAE, occurring before first dose of IgPro20.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	IgPro20
	Affected / at Risk (%)	# Events
Total	25/82 (30.49%)
Infections and infestations
Nasopharyngitis † 1	11/82 (13.41%)	13
Nervous system disorders
Headache † 1	4/82 (4.88%)	5
Skin and subcutaneous tissue disorders
Infusion site swelling † 1 [1]	9/82 (10.98%)	11
Infusion site erythema † 1 [1]	7/82 (8.54%)	9
Infusion site swelling † 1 [2]	9/82 (10.98%)	11
Infusion Site erythema † 1 [2]	7/82 (8.54%)	9
1 Term from vocabulary, MedDRA (14.1); † Indicates events were collected by systematic assessment; [1] General disorders and administration site conditions; [2] Local reactions

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Clinical Trial Disclosure Manager
• Organization: CSL Behring
• Phone: Use email contact
• EMail: clinicaltrials@cslbehring.com

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT02027701
• Other Study ID Numbers: IgPro20_3004; 2013-004157-24 ( EudraCT Number )
• First Submitted: January 3, 2014
• First Posted: January 6, 2014
• Results First Submitted: July 9, 2018
• Results First Posted: October 2, 2018
• Last Update Posted: October 2, 2018