Clinical Trial Results:
A Multicenter Follow-up Study of Long-term Safety, Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency
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Summary
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EudraCT number |
2014-003609-14 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
24 Apr 2012
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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 |
06 Aug 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 |
ZLB07_001CR
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01458171 | ||
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 |
1-13-1 Kachidoki, Chuo-ku, Tokyo, Japan, 104-0054
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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 |
23 May 2012
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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 |
24 Apr 2012
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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 safety, tolerability, and efficacy of IgPro20 in subjects with primary immunodeficiency (PID) as a follow-up to the pivotal study ZLB06_002CR (EUdraCT: 2014-003608-61, NCT01199705).
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Protection of trial subjects |
The study was conducted in accordance with the principles of the Ministry of Health and Welfare notification #28 (GCP, 27 March 1997) and YakuShokuShinsaHatsu Notification #1001001 (01 October 2000). The study was also carried out in keeping with requirements set forth in 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. GCP compliance was assessed during data review and confirmed in the Data Review Meeting (DRM). Compliance with these requirements also constitutes conformity with the ethical principles of the Declaration of Helsinki (version of 2008). The study was conducted under a protocol reviewed and approved by an Independent Ethics Committee/Institutional Review Board; the study was conducted by scientifically and medically qualified persons; the benefits of the study were in proportion to the risks; the rights and welfare of the subjects were respected; the physicians conducting the study did not find the hazards to outweigh the potential benefits; the results reported are accurate.
The investigator was responsible for obtaining written informed consent from the participating subject in accordance with Ministry of Health and Welfare notification #28 (GCP, 27 March 1997) and in compliance with the Declaration of Helsinki. Each subject and/or subject’s parent or legal guardian gave his or her written informed consent before any protocol-driven tests or evaluations were performed. The investigator could cease study treatment and withdraw the subject, or the subject could withdraw
themselves from participation in the study at any time. The decision to withdraw consent and discontinue participation in the study could not prejudice the subject’s future medical treatment in any way.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Apr 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: 23
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Worldwide total number of subjects |
23
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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) |
6
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
11
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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 nine study centers in Japan who had participated in the preceding pivotal study ZLB06_002CR (EudraCT: 2014-003608-61, CT.gov identifier: NCT01199705). | ||||||||||
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Pre-assignment
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Screening details |
Only subjects participating in the preceding pivotal study ZLB06_002CR were eligible. The enrolment visit of this study was on the same day as the completion visit of the preceding pivotal study ZLB06_002CR. | ||||||||||
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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 |
Immune globulin subcutaneous (Human): IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. Subjects will receive weekly infusions of IgPro20 for a total of 24 weeks at a dose based on the subject's IgPro20 dose in the pivotal study ZLB06_002CR (EudraCT 2014-003608-61, NCT01199705). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Immune globulin subcutaneous (Human)
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Investigational medicinal product code |
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Other name |
Hizentra, IgPro20
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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 SCIG. Each subject was to receive 24 weekly IgPro20 subcutaneous infusions in total. The weekly IgPro20 dose was equivalent to the subject’s last dose, recommended by the investigator, from pivotal study ZLB06_002CR. The IgPro20 dose could be adjusted if medically indicated or to ensure adequate IgPro20 trough levels.
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Baseline characteristics reporting groups
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Reporting group title |
IgPro20
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Reporting group description |
Immune globulin subcutaneous (Human): IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. Subjects will receive weekly infusions of IgPro20 for a total of 24 weeks at a dose based on the subject's IgPro20 dose in the pivotal study ZLB06_002CR (EudraCT 2014-003608-61, NCT01199705). | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IgPro20
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Reporting group description |
Immune globulin subcutaneous (Human): IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. Subjects will receive weekly infusions of IgPro20 for a total of 24 weeks at a dose based on the subject's IgPro20 dose in the pivotal study ZLB06_002CR (EudraCT 2014-003608-61, NCT01199705). | ||
Subject analysis set title |
IgPro20 - FAS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Full Analysis Set (FAS) comprised all subjects receiving at least 1 IgPro20 infusion.
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Subject analysis set title |
IgPro20 - PPS
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The Per Protocol Set (PPS) comprised all subjects with the disease under study who a) received uniformly repeated IgPro20 infusions at weekly intervals and b) who had at least 1 documented total serum IgG trough level.
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End point title |
Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion [1] | ||||||||||||||||||||
End point description |
The rate was calculated by counting all newly developed or worsened AEs within a subject and dividing by the total number of IgPro20 infusions administered to this subject. Subsequently, the median of these individual AE rates per infusion was calculated. AE rates were 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 |
Primary
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End point timeframe |
24 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: Variables were descriptively summarised. No formal statistical tests were planned or performed. |
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| Notes [2] - The All Treated (AT) set comprised all subjects receiving at least 1 IgPro20 infusion. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Overall Rate of AEs Per Infusion | ||||||||||||||||||||
End point description |
The rate was calculated by counting all newly developed or worsened AEs during the treatment period in all subjects and dividing the total number of AEs by the total number of IgPro20 infusions administered. In addition, individual AEs were 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]). The AE rates per infusion by severity and causal relationship to study medication were calculated by dividing the number of AEs in each category by the total number of IgPro20 infusions.
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End point type |
Secondary
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End point timeframe |
24 weeks
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| Notes [3] - The AT set = all subjects receiving at least 1 IgPro20 infusion. Number of Infusions Analyzed = 529 |
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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 AEs | ||||||||||||||||||
End point description |
Number of subjects with AEs, 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 |
24 weeks
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| Notes [4] - The AT set comprised all subjects receiving at least 1 IgPro20 infusion. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Infusions With Subject-assessed Tolerability of at Least 'Good' | ||||||||
End point description |
Subjects assessed their overall perception of local tolerability at the infusion site throughout the study in the subject diary within a time window of 24 h to 72 h after the end of the latest infusion by assessing it as “very good”, “good”, “fair”, or “poor”. The reported end point represents the percentage of infusions for which subjects' overall perception of local tolerability was "very good" or "good" at any given study infusion.
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End point type |
Secondary
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End point timeframe |
24 to 72 hours after infusion
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| Notes [5] - The FAS comprised all subjects receiving at least 1 IgPro20 infusion. |
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| No statistical analyses for this end point | |||||||||
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End point title |
IgG Trough Level | |||||||||||||||||||||
End point description |
Serum IgG trough levels at the completion visit compared to the baseline visit of the follow-up study. IgG trough levels at baseline, at the completion visit, and the change from baseline to the completion visit are shown
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End point type |
Secondary
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End point timeframe |
24 weeks
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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 and PPS and adjusted to 365 days.
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End point type |
Secondary
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End point timeframe |
24 weeks
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| Notes [6] - Number of total study days analyzed: 3739 [7] - Number of Total Study Days Analyzed: 3214 |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Infection Episodes (Serious and Non-serious) | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 weeks
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections | ||||||||||||
End point description |
Median number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections.
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End point type |
Secondary
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End point timeframe |
24 weeks
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| Notes [8] - PPS |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Days of Hospitalization Due to Infections | ||||||||||||
End point description |
Median number of days of hospitalization due to infections.
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End point type |
Secondary
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End point timeframe |
24 weeks
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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 |
Median number of days of use of antibiotics for infection prophylaxis and/or treatment.
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End point type |
Secondary
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End point timeframe |
24 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Rate of Infection Episodes (Serious and Non-serious) | ||||||||||||
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 population and the PPS population and adjusted to 365 days.
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End point type |
Other pre-specified
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End point timeframe |
24 weeks
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| Notes [9] - Number of total study days analyzed: 3739 [10] - Number of total study days analyzed: 3214 |
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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, 24 weeks.
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Adverse event reporting additional description |
Only AEs starting at or after the first study drug infusion are included. The AT set comprised all subjects receiving at least 1 IgPro20 infusion.
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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 |
Immune globulin subcutaneous (Human): IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. Subjects will receive weekly infusions of IgPro20 for a total of 24 weeks at a dose based on the subject's IgPro20 dose in the pivotal study ZLB06_002CR (EudraCT 2014-003608-61, NCT01199705). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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11 Feb 2011 |
There was 1 amendment to the original study protocol that was implemented prior to study start and to inclusion of any subjects. All subjects in the study were treated according to the final study protocol following Amendment 1 (i.e., CSP version 2.0) dated 11 February 2011. The main changes are summarized
below:
• An extension to the study objectives to include the HRQL and PhEc assessments.
• Clearer illustration of the mode of administration.
• A change to the number of planned subjects for enrollment into the study from “15” to “20 to 25” subjects.
• Clearer subcategories for casual relationship and severity.
• Change to the schedule for completion of the questionnaires. |
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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 | |||
