Trial Outcomes & Findings for Extension Study of Maintenance Treatment With Subcutaneous Immunoglobulin (IgPro20) for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (NCT NCT02027701)

NCT ID: NCT02027701

Last Updated: 2018-10-02

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 82 participants
• Primary outcome timeframe: Up to 49 weeks
• Results posted on: 2018-10-02

Participant Flow

Participant milestones

Measure	IgPro20 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.
Overall Study STARTED	82
Overall Study COMPLETED	66
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Measure	IgPro20 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.
Overall Study Adverse Event	3
Overall Study Lack of Efficacy	8
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	IgPro20 n=82 Participants 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.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	55 Participants n=93 Participants
Age, Categorical >=65 years	27 Participants n=93 Participants
Age, Continuous	57.57 years STANDARD_DEVIATION 13.224 • n=93 Participants
Sex: Female, Male Female	32 Participants n=93 Participants
Sex: Female, Male Male	50 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants
Race (NIH/OMB) Asian	10 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	70 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Region of Enrollment Canada	7 participants n=93 Participants
Region of Enrollment Netherlands	1 participants n=93 Participants
Region of Enrollment United States	9 participants n=93 Participants
Region of Enrollment Czechia	2 participants n=93 Participants
Region of Enrollment Japan	10 participants n=93 Participants
Region of Enrollment Italy	8 participants n=93 Participants
Region of Enrollment United Kingdom	4 participants n=93 Participants
Region of Enrollment Australia	1 participants n=93 Participants
Region of Enrollment France	1 participants n=93 Participants
Region of Enrollment Germany	29 participants n=93 Participants
Region of Enrollment Spain	10 participants n=93 Participants

PRIMARY outcome

Timeframe: Up to 49 weeks

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

Outcome measures

Measure	IgPro20 n=5553 Infusions 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.
Number of Adverse Events (AEs) Per Infusion	0.032 Adverse events per infusion

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: 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.

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).

Outcome measures

Measure	IgPro20 n=82 Participants 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.
Time to First CIDP Relapse	266.0 Days Interval 225.0 to 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.

SECONDARY outcome

Timeframe: Baseline and up to 49 weeks

Population: Total Set

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.

Outcome measures

Measure	IgPro20 n=80 Participants 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.
Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Score	0.0 units on a scale Interval -3.0 to 6.0

SECONDARY outcome

Timeframe: Baseline and up to 49 weeks

Population: Total Set

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.

Outcome measures

Measure	IgPro20 n=78 Participants 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.
Change From Baseline in Medical Research Council (MRC) Score	0.0 units on a scale Interval -23.0 to 18.0

SECONDARY outcome

Timeframe: Baseline and up to 49 weeks

Population: Total Set

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.

Outcome measures

Measure	IgPro20 n=71 Participants 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.
Change From Baseline in Rasch-built Overall Disability Scale (R-ODS)	0.0 units on a scale Interval -76.0 to 33.0

SECONDARY outcome

Timeframe: Baseline and up to 49 weeks

Population: Total Set

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.

Outcome measures

Measure	IgPro20 n=79 Participants 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.
Change From Baseline in Mean Grip Strength	-0.7 kPa Interval -80.0 to 27.0

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: SDS

Outcome measures

Measure	IgPro20 n=82 Participants 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.
Percentage of Subjects With Adverse Events (AEs)	75.6 percentage of subjects

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: SDS

Outcome measures

Measure	IgPro20 n=5553 Infusions 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.
Number of AEs by Severity Per Infusion Mild	0.024 Adverse events per infusion
Number of AEs by Severity Per Infusion Moderate	0.006 Adverse events per infusion
Number of AEs by Severity Per Infusion Severe	0.002 Adverse events per infusion

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: SDS

Outcome measures

Measure	IgPro20 n=82 Participants 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.
Percentage of Subjects With AEs by Severity Mild	62.2 percentage of subjects
Percentage of Subjects With AEs by Severity Moderate	29.3 percentage of subjects
Percentage of Subjects With AEs by Severity Severe	9.8 percentage of subjects

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: SDS

Outcome measures

Measure	IgPro20 n=5553 Infusions 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.
Number of Causally Related AEs Per Infusion	0.011 Adverse events per infusion

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: SDS

Outcome measures

Measure	IgPro20 n=82 Participants 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.
Percentage of Subjects With Causally Related AEs	25.6 percentage of subjects

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: SDS

Outcome measures

Measure	IgPro20 n=5553 Infusions 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.
Number of Serious AEs Per Infusion	0.001 Adverse events per infusion

SECONDARY outcome

Timeframe: Up to 49 weeks

Population: SDS

Outcome measures

Measure	IgPro20 n=82 Participants 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.
Percentage of Subjects With Serious AEs	8.5 percentage of subjects

Adverse Events

IgPro20

Serious events: 7 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	IgPro20 n=82 participants at risk 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.
Hepatobiliary disorders Gallbladder Perforation	1.2% 1/82 • Number of events 1 • Up to 49 weeks
Cardiac disorders Atrial Flutter	2.4% 2/82 • Number of events 2 • Up to 49 weeks
Nervous system disorders Nerve Compression	1.2% 1/82 • Number of events 1 • Up to 49 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary Sepsis	1.2% 1/82 • Number of events 1 • Up to 49 weeks
Renal and urinary disorders Urinary Tract Infection	1.2% 1/82 • Number of events 1 • Up to 49 weeks
Gastrointestinal disorders Faecaloma	1.2% 1/82 • Number of events 1 • Up to 49 weeks
Immune system disorders Chronic Inflammatory Demyelinating Polyradiculoneuropathy	1.2% 1/82 • Number of events 1 • Up to 49 weeks
Musculoskeletal and connective tissue disorders Back Pain	1.2% 1/82 • Number of events 1 • Up to 49 weeks

Other adverse events

Measure	IgPro20 n=82 participants at risk 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.
Skin and subcutaneous tissue disorders Infusion site swelling	11.0% 9/82 • Number of events 11 • Up to 49 weeks
Skin and subcutaneous tissue disorders Infusion site erythema	8.5% 7/82 • Number of events 9 • Up to 49 weeks
Skin and subcutaneous tissue disorders Infusion Site erythema	8.5% 7/82 • Number of events 9 • Up to 49 weeks
Infections and infestations Nasopharyngitis	13.4% 11/82 • Number of events 13 • Up to 49 weeks
Nervous system disorders Headache	4.9% 4/82 • Number of events 5 • Up to 49 weeks

Additional Information

Clinical Trial Disclosure Manager

CSL Behring

Phone: Use email contact

Email: clinicaltrials@cslbehring.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER