Clinical Trial Results:
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
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Summary
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EudraCT number |
2013-004157-24 |
Trial protocol |
GB IT DE ES FI NL CZ |
Global end of trial date |
10 Jul 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Jul 2018
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First version publication date |
25 Jul 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
IgPro20_3004
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT02027701 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CSL Behring GmbH
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Sponsor organisation address |
Emil-von-Behring-Strasse 76, Marburg, Germany,
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Public contact |
Clin Trial Registration Coordinator, CSL Behring GmbH, clinicaltrials@cslbehring.com
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Scientific contact |
Clin Trial Registration Coordinator, CSL Behring GmbH, clinicaltrials@cslbehring.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Aug 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jul 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate long-term safety and efficacy of IgPro20.
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Protection of trial subjects |
This study was carried out in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and standard operating procedures for clinical research and development at CSL Behring, LLC (CSLB).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Jul 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 10
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
United States: 9
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Country: Number of subjects enrolled |
Australia: 1
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Country: Number of subjects enrolled |
Canada: 7
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Country: Number of subjects enrolled |
Czech Republic: 2
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Germany: 29
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Country: Number of subjects enrolled |
Italy: 8
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Country: Number of subjects enrolled |
Japan: 10
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Country: Number of subjects enrolled |
Netherlands: 1
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Worldwide total number of subjects |
82
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EEA total number of subjects |
55
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
55
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From 65 to 84 years |
27
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
Subject had completed Study 3003 (SC Week 25) or was successfully rescued from a relapse during the SC Treatment Period of Study 3003, and if treatment for CIDP was required it had to include IgGs. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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IgPro20 | ||||||||||||||||
Arm 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. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
IgPro20
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
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.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IgPro20
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Reporting 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. | ||
Subject analysis set title |
Safety Data Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety Data Set (SDS): all subjects who received at least 1 dose of IgPro20 in this study.
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Subject analysis set title |
Total Set
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set 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.
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End point title |
Overall rate of Adverse Events (AEs) per infusion (SDS) [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Up to 49 weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were given for this outcome measure. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CIDP Total Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Score (Total Set) | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline and up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Medical Research Council (MRC) Score (Total Set) | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline and up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Rasch-built Overall Disability Scale (R-ODS) (Total Set) | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline and up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Mean Grip Strength (Total Set) | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline and up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Rate of AEs by Severity Per Infusion (SDS) | ||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 49 weeks
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Rate of Causally Related AEs Per Infusion (SDS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Rate of Serious AEs Per Infusion (SDS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Adverse Events (AEs) (SDS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with AEs by Severity (SDS) | ||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 49 weeks
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percentage of Subjects with Causally Related AEs (SDS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with AEs by Seriousness (SDS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 49 weeks
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 49 weeks
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
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Reporting groups
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Reporting group title |
IgPro20
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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31 Jul 2014 |
•Study design modified to require direct transition from the completion visit of study IgPro20_3003 to the Week 1 (baseline) visit of this study.
•Inclusion criteria modified to define the study population (subjects who completed the SC Period or successfully recovered from CIDP relapse during the SC Period of the IgPro20_3003 study).
•Exclusion criteria modified because of study design change, ie, direct transition from study IgPro20_3003.
•IgPro20 dose reduced to 0.2 g/kg bw; if CIDP relapse occurs, subject will have the dose adjusted up to 0.4 g/kg bw; subject must successfully recover within 4 weeks (±2 days) in order to continue in the study. Dose justification and maximum volume per infusion site increased to 50 mL, as tolerated.
•Subjects enrolled under the original protocol will be re-consented for Amendment 1 and started on Amendment 1 dose requirements and procedures at Week 25. If a subject enrolled under the original protocol, relapses and successfully recovers from the relapse prior to Week 25, the subject will remain on 0.4 g/kg bw for the remainder of the study. If the subject relapses again, they will be discontinued.
•Week 17 and Week 41 visits converted to dispensing and inventory only visits.
•Viral safety testing deleted, only retention sample collected for possible future testing if a suspected treatment-emergent viral infection occurs.
•Biomarker text modified to delete anonymization of samples. This should not have been required in the original protocol, because no genetics will be tested. Biomarker results will need to be correlated with the subject’s treatment in both studies and other test results in order to benefit understanding of CIDP disease progression and how to treat it. Biomarker sample collection is optional for Japan.
•Missing efficacy (R-ODS) and HRQL (EQ-5D) instruments added to Section 8 and the Appendix, respectively.
•Statement added that IgG levels will not be disclosed to the site or CSLB until the IgP |
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22 Jun 2015 |
•Number of subjects increased to approximately 80 subjects.
•IVRS language updated to more closely align with the IgPro20_3003 protocol.
•Biomarker language modified to confirm that a biomarker sample is required to be collected upon a CIDP relapse, either at a scheduled visit, or an unscheduled visit whichever is more timely. An unscheduled laboratory kit should be used for biomarker sample collection for both scheduled and unscheduled visits.
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08 Dec 2015 |
•Adverse reactions were updated per current safety information.
•IVRS language updated to clarify volume needed for each infusion session.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| For the "Endpoint Time to First CIDP Relapse (Total Set)", the subjects analyzed is 82, subjects started is 82, median is 266.0, 95%CI is 225.0 to NA (not evaluable). | |||
