Clinical Trial Results:
A Multicenter Extension Study on the Safety and Efficacy of IgPro10 in Patients With Primary Immunodeficiency (PID)
|
Summary
|
|
EudraCT number |
2014-003772-23 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
16 Apr 2008
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
13 Jul 2016
|
First version publication date |
06 Aug 2015
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ZLB05_006CR
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00322556 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
CSL Behring AG
|
||
Sponsor organisation address |
Wankdorfstrasse 10, Berne 22, Switzerland, CH-3000
|
||
Public contact |
Clinical Trial Disclosure Manager, CSL Behring, clinicaltrials@cslbehring.com
|
||
Scientific contact |
Clinical Trial Disclosure Manager, CSL Behring, clinicaltrials@cslbehring.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
09 Jul 2008
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
16 Apr 2008
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To assess the safety and efficacy of IgPro10 in patients with PID, and to assess the tolerability of a high infusion rate.
|
||
Protection of trial subjects |
This study was carried out in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice guidelines, and standard operating procedures for clinical research and development at CSL Behring (CSLB). The study protocol and all amendments were approved by the Independent Ethics Committee(s) (IECs) / Institutional Review Board(s) (IRBs) of the participating
centers. 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.
The investigator may cease study treatment and withdraw the subject, or the subject may withdraw himself from participation in the study at any time. If a subject is withdrawn from the study or further participation is declined, the subject will continue to have access to medical care and will be treated according to routine medical practice, but will no longer receive the investigational medicinal
product (IMP).
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Nov 2005
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 55
|
||
Worldwide total number of subjects |
55
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
13
|
||
Adolescents (12-17 years) |
11
|
||
Adults (18-64 years) |
27
|
||
From 65 to 84 years |
4
|
||
85 years and over |
0
|
||
|
|||||||||||||||||
|
Recruitment
|
|||||||||||||||||
Recruitment details |
- | ||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||
Screening details |
For subjects joining from study ZLB03_002CR, Screening was done between the completion visit for that study and the first infusion for study ZLB05_006CR (2014-003772-23), including both days. For ‘new’ subjects, Screening was done 1 to 30 days before the first infusion with IgPro10 for study ZLB05_006CR. | ||||||||||||||||
|
Period 1
|
|||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||
|
Arms
|
|||||||||||||||||
|
Arm title
|
IgPro10 | ||||||||||||||||
Arm description |
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
IgPro10
|
||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||
Other name |
human normal immunoglobulin, Privigen®
|
||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||
Dosage and administration details |
IgPro10 was administered every 3 or 4 weeks using an individualized regimen with a dose of 0.2 – 0.8 g IgG per kg body weight.
|
||||||||||||||||
|
|||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IgPro10
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study. | |||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
IgPro10
|
||
Reporting group description |
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study. | ||
Subject analysis set title |
IgPro10 (≤ 4 mg/kg/Min)
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study, at the maximum infusion rate (≤ 4 mg/kg/min) for new subjects.
|
||
Subject analysis set title |
IgPro10 (≤ 8 mg/kg/Min)
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study, at the low maximum infusion rate (≤ 8 mg/kg/min) for old subjects.
|
||
Subject analysis set title |
IgPro10 (> 8 to ≤ 12 mg/kg/Min)
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study, at the high maximum infusion rate (> 8 and ≤ 12 mg/kg/min) for old subjects.
|
||
|
|||||||||||||||
End point title |
Proportion of Infusions With One or More Temporally-associated Adverse Events (AEs) [1] | ||||||||||||||
End point description |
AEs were considered temporally-associated AEs if they occurred during the infusion or in the period from the start of the infusion until either 48 or 72 hours after the end of the infusion. The Safety Data Set (SDS) comprised all subjects treated with the study drug.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
During each infusion, and within 48 or 72 hours after the end of each infusion.
|
||||||||||||||
| 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: Descriptive statistics are reported for this end point. |
|||||||||||||||
|
|||||||||||||||
| Notes [2] - Number of infusions analyzed: 771 |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Influence of Infusion Rate on Temporally-associated AEs [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The total and most frequent (1% or more) number of infusions for which subjects experienced temporally-associated AEs occurring within 72 hours of infusion, by infusion rate (≤ 4 mg/kg/min, ≤ 8 mg/kg/min, and > 8 and ≤ 12 mg/kg/min).
AEs were considered to be temporally-associated AEs if they occurred in the period from the start of the infusion until 72 hours after the end of the infusion.
'New subjects’ could receive IgPro10 at up to 4 mg/kg/min. Subjects treated with the study drug who participated in a preceding, pivotal, Phase III clinical study with intravenous IgPro10 (study number ZLB03_002CR, NCT00168025) could receive IgPro10 at up to 12 mg/kg/min at the discretion of the Investigator.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Within 72 hours after each infusion
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [3] - 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: Descriptive statistics are reported for this end point. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [4] - Number of infusions analyzed: 81 [5] - Number of infusions analyzed: 423 [6] - Number of infusions analyzed: 265 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||
End point title |
Rate of AEs by Severity and Relationship [7] | ||||||||||||||||||||||||||||||||||
End point description |
The AE rate was the number of AEs over the number of infusions administered.
Mild AEs: Did not interfere with daily activities; Moderate AEs: Interfered with routine daily activities; Severe AEs: Impossible to perform routine daily activities.
At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.
The SDS comprised all subjects treated with the study drug.
|
||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||
End point timeframe |
For the duration of the study, up to approximately 29 months
|
||||||||||||||||||||||||||||||||||
| Notes [7] - 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: Descriptive statistics are reported for this end point. |
|||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||
| Notes [8] - Number of infusions analyzed: 771 |
|||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
|
|||||||
End point title |
Number of Subjects With Clinically Significant Changes in Vital Signs [9] | ||||||
End point description |
Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.
The SDS comprised all subjects treated with the study drug.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
Before, during, and after each infusion.
|
||||||
| Notes [9] - 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: Descriptive statistics are reported for this end point. |
|||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||
End point title |
Annualized Rate of Acute Serious Bacterial Infections | ||||||||
End point description |
The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Acute serious bacterial infections included pneumonia, bacteremia / septicemia, osteomyelitis / septic arthritis, bacterial meningitis, and visceral abscess.
The Intention-To-Treat (ITT) data set comprised all subjects treated with the study drug.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
For the duration of the study, up to approximately 29 months
|
||||||||
|
|||||||||
| Notes [10] - Number of subject study days analyzed:20757 |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Illness | ||||||||
End point description |
The ITT data set comprised all subjects treated with the study drug. The patient diary (in which the number of days was recorded) was not available for 1 subject so the analyzed population was reduced from 55 to 54 subjects for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
For the duration of the study, up to approximately 29 months.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Number of Days of Hospitalization | ||||||||
End point description |
The ITT data set comprised all subjects treated with the study drug. The patient diary (in which the number of days was recorded) was not available for 1 subject so the analyzed population was reduced from 55 to 54 subjects for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
For the duration of the study, up to approximately 29 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Annualized Rate of Any Infection | ||||||||
End point description |
The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Infections were classified as all AEs with the system organ class “infections and infestations” and AEs with the preferred term “conjunctivitis.”
The ITT data set comprised all subjects treated with the study drug.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
For the duration of the study, up to approximately 29 months.
|
||||||||
|
|||||||||
| Notes [11] - Number of subject study days analyzed: 20757 |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Trough Levels of Total Immunoglobulin (IgG) Serum Concentrations | ||||||||
End point description |
Mean IgG trough concentration. For this analysis, each subject’s values were first aggregated to their median and the median values were then analyzed.
The ITT data set comprised all subjects treated with the study drug for which serum IgG information was available.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Prior to each infusion; every 3 or 4 weeks depending upon the dosing schedule.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
For the duration of the study, up to approximately 29 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Only AEs starting at or after the first study drug infusion were included. The SDS comprised all subjects treated with the study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IgPro10
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
11 Jul 2006 |
Recruitment for the study was expanded from an estimated 30 subjects to an estimated 40 to 60 subjects.
The duration for the study was extended until the time when all sites were to be open for the ZLB04_009CR (2014-003607-30) study. This caused the study duration per subject to increase from < 9 months to a variable time dependent upon the time slot between a subject’s last infusion within ZLB03_002CR and the regulatory and IRB approvals of the ZLB04_009CR study.
Amendment 1 described the inclusion of new subjects who would later be enrolled into the pharmacokinetic (PK) substudy ZLB04_009CR. The PK endpoints, inclusion/exclusion criteria, subject identification, and dosing schedule were added. The study objectives were also updated to reflect the purpose of the PK inclusion. |
||
29 Mar 2007 |
The time of duration for the study was extended from the time when all sites were opened for the ZLB04_009CR SCIG study to the time when IgPro10 was launched in the United States (US). Previously, subjects were only offered to switch to the subcutaneous Ig (SCIg) study. This change allowed current subjects on the study the alternative option to remain in the protocol until IgPro10 was launched in the US.
The Sponsor name was changed to CSL Behring to keep in line with corporate changes. Changes in study personnel on both the Sponsor and contract research organization levels were reflected. Other changes to the clinical study protocol introduced an interim analysis and provided clarification of the scope of statistical analyses. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
