Clinical Trial Results:
A Multicenter Study of Long-Term Clinical Outcomes of Immune Globulin Subcutaneous (Human) (SCIG) IgPro20 in Subjects with Primary Immunodeficiency
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Summary
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EudraCT number |
2014-003409-13 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
22 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Jul 2016
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First version publication date |
18 Feb 2015
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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_3006
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CSL Behring K.K.
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Sponsor organisation address |
KDX Toyosu Grandsquare, 1-7-12 Shinonome, Koto-ku, Tokyo, Japan, 135-0062
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Public contact |
Trial Registration Co-ordinator, CSL Behring, clinicaltrials@cslbehring.com
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Scientific contact |
Trial Registration Co-ordinator, CSL Behring, 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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Oct 2014
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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 |
22 Jul 2014
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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 assess the long-term efficacy, tolerability, and safety of IgPro20 in subjects with primary immunodeficiency (PID) as an extension to the preceding follow-up study ZLB07_001CR.
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Protection of trial subjects |
The study was conducted in accordance with the principles of the Ministry of Health, Labor, and Welfare (Japan, MHLW) Notification #28 (Good Clinical Practice [GCP], 27 March 1997), YakuShokuShinsaHatsu Notification #1001001 (01 October 2010), and the Declaration of Helsinki (version of 2008). The study was also carried out in keeping with requirements set forth in the Pharmaceutical Affairs Law 14-3 and 80-2. In addition, this study was conducted in accordance with the International Conference on Harmonisation (ICH) GCP guidelines, and Standard Operating Procedures (SOPs) for clinical research and development at CSL Behring and the clinical research organizations involved. The study protocol and all amendments were approved by an Independent Ethics Committee(s) (IECs) / Institutional Review Board(s) (IRBs). Before undergoing screening procedures for possible enrollment into the study, subjects were informed, in an understandable form, about the nature, scope, and possible consequences of the study. The investigator was responsible for obtaining a subject’s written informed consent to participate in the study.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Oct 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Japan: 22
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Worldwide total number of subjects |
22
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EEA total number of subjects |
0
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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) |
5
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Adolescents (12-17 years) |
5
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Adults (18-64 years) |
12
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This multicenter study enrolled subjects at 9 study centers in Japan who had participated in the preceding follow-up study ZLB07_001CR (CT.gov identifier: NCT01458171). | ||||||||||||||
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Pre-assignment
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Screening details |
Only subjects participating in the preceding follow-up study ZLB07_001CR were eligible. Enrolment visit of this study was on same day as completion visit of the preceding follow-up study ZLB07_001CR. | ||||||||||||||
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Period 1
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Period 1 title |
Overall (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 |
IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Hizentra®
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Investigational medicinal product code |
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Other name |
Human Normal Immunoglobulin, Immune globulin subcutaneous (Human)
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use.
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Baseline characteristics reporting groups
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Reporting group title |
Overall
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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 |
IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. | ||
Subject analysis set title |
FAS (Full analysis set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The FAS comprised all subjects receiving at least 1 IgPro20 infusion.
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Subject analysis set title |
PPS (Per protocol set)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PPS population comprised all subjects with the disease under study who a) received uniformly repeated IgPro20 infusions at weeks intervals and b) who had at least 1 documented total serum IgG trough level.
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End point title |
Annualized rate of infection episodes (serious and non-serious) [1] | ||||||||||||
End point description |
The annualized rate of infection episodes (serious and non-serious) was based on the total number of infection episodes and the total number of subject study days for all subjects in the FAS and the PPS and adjusted to 365 days.
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End point type |
Primary
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End point timeframe |
Up to 36 months
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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: Variables were descriptively summarised. No formal statistical tests were planned or performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects with newly developing or worsening adverse events (AEs) | ||||||||||||||||
End point description |
Number of subjects with newly developing or worsening AEs, overall and classified (i) by severity (mild, moderate, severe) and (ii) by causal relationship to study medication (at least possibly related [i.e., possibly related, probably related, or related]).
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of subjects with newly developing or worsening adverse events (AEs) | ||||||||||||||||||
End point description |
Percentage of subjects with newly developing or worsening AEs, overall and classified (i) by severity (mild, moderate, severe) and (ii) by causal relationship to study medication (at least possibly related [i.e., possibly related, probably related, or related]).
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Rate of AEs per infusion | ||||||||||||||||||||
End point description |
Rate of adverse events per infusion, overall and classified (i) by severity (mild, moderate, severe) and (ii) by causal relationship to study medication (not related or unlikely related; at least possibly related [i.e., possibly related, probably related, or related]).
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Annualized rate of clinically documented serious bacterial infections (SBIs) | ||||||||||||
End point description |
SBIs are defined as bacterial pneumonia, bacteremia and septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess. The annualized rate was based on the total number of SBIs and the total number of subject study days for all subjects in the FAS (N=22) and PPS (N=17) and adjusted to 365 days.
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Annualized rate of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections | ||||||||||||
End point description |
The annualized rate was based on the total number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections and the total number of subject study days for all subjects in the FAS and PPS and adjusted to 365 days.
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Annualized rate of days of hospitalization due to infections | ||||||||||||
End point description |
The annualized rate was based on the total number of days hospitalized and the total number of subject study days for all subjects in the FAS and PPS and adjusted to 365 days.
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Duration of use of antibiotics for infection prophylaxis and treatment | ||||||||||||
End point description |
The annualized rate was based on the total number of days treated with antibiotics and the total number of subject study days for all subjects in the FAS and PPS and adjusted to 365 days.
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Median serum IgG concentration | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 36 months
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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 |
For the duration of the study, that is, up to 36 months per subject.
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Adverse event reporting additional description |
Only AEs starting at or after the first study drug infusion are included. A total of 2660 infusions of IgPro20 were administered to 22 subjects.
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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 |
IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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22 May 2013 |
There was 1 amendment to the original study protocol that was implemented during the study. The main changes were:
1. Change in regulatory status of the study from “phase 3 study” to “post-marketing approval study” after approval of IgPro20 in Japan, in compliance with Japanese regulations.
2. Extension of expected maximum study duration from “30” to “36” months, until availability of IgPro20 on the market in Japan. |
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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. | |||
| None reported | |||
