Clinical Trial Results:
A Multicenter Extension Study of the Efficacy, Tolerability, and Safety of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects with Primary Immunodeficiency (IgPro20 EU Extension Study)
Summary
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EudraCT number |
2008-000830-30 |
Trial protocol |
DE ES FR SE GB |
Global end of trial date |
21 Dec 2011
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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 |
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_002CR
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00751621 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
CSL Behring AG
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Sponsor organisation address |
Wankdorfstrasse 10, Bern 22, Switzerland, 3000
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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 |
10 Apr 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 |
21 Dec 2011
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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 |
This study is a continuation of the study ZLB06_001CR with the objective of assessing efficacy, tolerability, safety of IgPro, as well as long-term health-related quality of life in patients with PID.
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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, the Declaration of Helsinki (version of 1996), and standard operating procedures for clinical research and development at CSL Behring and the Clinical Research Organizations involved. The study was conducted under a protocol reviewed and approved by an IEC/IRB. 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; and each subject or subject’s parent or legal guardian gave his or her written informed consent before any protocol-driven tests or evaluations were performed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Aug 2008
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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 |
Poland: 7
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
Sweden: 1
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Switzerland: 1
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Country: Number of subjects enrolled |
Romania: 10
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Worldwide total number of subjects |
40
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EEA total number of subjects |
39
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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) |
15
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Adolescents (12-17 years) |
7
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Adults (18-64 years) |
18
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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 |
Subjects who had previously participated in the pivotal study ZLB06_001CR (NCT00542997) were enrolled in the extension study ZLB07_002CR. | ||||||||||||||||
Pre-assignment
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Screening details |
The number of subjects and sites was dependent on the subjects’ and sites’ interest to continue the IgPro20 treatment following the pivotal study ZLB06_001CR. | ||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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IgPro20 | ||||||||||||||||
Arm description |
Subcutaneous (SC) administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
IgPro20
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Investigational medicinal product code |
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Other name |
IgG with Proline (IgPro), Hizentra
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR.
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Baseline characteristics reporting groups
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Reporting group title |
IgPro20
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Reporting group description |
Subcutaneous (SC) administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IgPro20
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Reporting group description |
Subcutaneous (SC) administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR. | ||
Subject analysis set title |
HRQL - At Baseline
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Baseline values for those subjects in the Full-Analysis health related quality of life (HRQL) data set (defined as all subjects entered into the study who complete a baseline and at least 1 follow-up HRQL assessment), who were at least 15 years of age.
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Subject analysis set title |
HRQL - At End of Study
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
End of study values for subjects in the Full-Analysis HRQL data set (defined as all subjects entered into the study who complete a baseline and at least 1 follow-up HRQL assessment), who were at least 15 years of age.
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End point title |
Total Serum IgG Trough Levels [1] | ||||||||
End point description |
The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
The full analysis/intent to treat (ITT) dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Primary
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End point timeframe |
Up to 42 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 summarized using descriptive statistics. |
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Notes [2] - ITT population |
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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 |
The annualized rate was based on the total number of SBIs and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Potential SBIs included bacterial pneumonia, bacteremia and septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by the Medical Monitor and Investigator to determine if the event fulfilled the predefined criteria for SBIs.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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Notes [3] - Number of subject study days analyzed: 38208 |
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No statistical analyses for this end point |
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End point title |
Annualized Rate of Infection Episodes | ||||||||
End point description |
The annualized rate was based on the total number of infection episodes occurring during the study divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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Notes [4] - ITT population. Number of Subject Study Days Analyzed: 38208 |
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No statistical analyses for this end point |
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End point title |
Number of Infection Episodes | ||||||
End point description |
Total number of infections for the ITT population.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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Notes [5] - ITT population |
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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 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 inability to perform normal activities due to infection, and the total number of subject diary days for all subjects in the ITT population and adjusted to 365 days.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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Notes [6] - ITT population Number of Subject Diary Days Analyzed: 38045 |
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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 Activities Due to Infections | ||||||
End point description |
Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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Notes [7] - ITT population |
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No statistical analyses for this end point |
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End point title |
Annualized Rate of Hospitalization Due to Infections | ||||||||
End point description |
The annualized rate was based on the total number of days of hospitalization due to infections and the total number of subject diary days for all subjects in the specified analysis population and adjusted to 365 days.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
up to 42 months
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Notes [8] - ITT population. Number of Subject Diary Days Analyzed: 38045 |
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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 |
Total number of days of hospitalization due to infections for the ITT population.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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Notes [9] - ITT population |
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No statistical analyses for this end point |
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End point title |
Use of Antibiotics for Infection Prophylaxis and Treatment | ||||||||
End point description |
Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the ITT population, and adjusted to 365 days.
The full analysis/ITT dataset comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
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End point type |
Secondary
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End point timeframe |
up to 42 months
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Notes [10] - ITT population Number of Subject Study Days Analyzed: 38208 |
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No statistical analyses for this end point |
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End point title |
Health Related Quality of Life (Short Form 36 Health Survey) | ||||||||||||||||||||||||||||||||||||
End point description |
The Short Form 36 Health Survey is a 36-item questionnaire that measures generic health concepts that are relevant across age, disease, and treatment groups. The questions are grouped into eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100, with higher scores indicating a better health state.
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End point type |
Secondary
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End point timeframe |
At baseline and at the last available post-baseline observation for each subject (up to 42 months)
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No statistical analyses for this end point |
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End point title |
Clinically Relevant Changes in Vital Signs From Baseline to the Completion Visit | ||||||
End point description |
The total number of subjects with clinically relevant changes in vital signs from baseline to the completion visit. Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.
The 'All Treated' (AT) safety data set included all subjects treated with study drug.
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End point type |
Secondary
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End point timeframe |
At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months)
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Notes [11] - AT population, reporting subjects with data collected at both baseline and completion |
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No statistical analyses for this end point |
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End point title |
Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit | ||||||||||||
End point description |
The total number of subjects with clinically significant abnormal changes in routine laboratory parameters between baseline and the completion visit. Routine laboratory parameters included haematology, serum chemistry and urinalysis.
The AT safety data set included all subjects treated with study drug.
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End point type |
Secondary
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End point timeframe |
At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months)
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Notes [12] - AT population, reporting subjects with data collected at both baseline and completion |
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No statistical analyses for this end point |
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End point title |
Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | ||||||||||||||||||||||
End point description |
The rate of AEs was the number of AEs over the number of infusions administered. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.
The AT safety data set included all subjects treated with study drug.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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Notes [13] - AT population. Number of Infusions Analyzed: 5405 |
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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 |
AEs were collected for the duration of the study, up to 42 months.
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Adverse event reporting additional description |
A total of 5405 weekly infusions of IgPro20 were administered to 40 subjects in this study. Three subjects received fewer than 100 infusions. The AT safety data set comprised all subjects treated with IgPro20 during any study period.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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09 Jan 2009 |
This protocol amendment included the change of the supervising investigator for Germany (Leiter der klinischen Prüfung according to German drug law) and the biometrics service provider as well as several minor editorial changes. |
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13 Jan 2009 |
This was a country-specific amendment applicable for study sites in the UK. To fulfill the requirements of the MHRA, the study duration was defined as exactly 30 months. |
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13 Jan 2009 |
This was a country-specific amendment applicable for study sites in Sweden. To fulfill the requirements of the Swedish Competent Authorities
(Läkemedelsverket), the study duration was defined as exactly 30 months. Additionally, the investigators were advised to contact subjects by telephone between the 6 monthly visits.
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06 Jul 2009 |
This amendment included an increase in the maximum storage temperature of IgPro20, a switch from 50 mL IgPro20 bottles to 20 mL bottles, and a clarification concerning calculation of the visit intervals. |
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06 Dec 2010 |
This was a country-specific amendment applicable for all study sites, except the UK. The individual study duration depended on the time between last infusion within study ZLB06_001CR and the availability of IgPro20 on the European market, and could vary from country to country. The study duration was originally expected to not exceed 30 months, but was defined as not exceeding 42 months by this amendment.
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14 Mar 2011 |
This was a country-specific amendment applicable for study sites in the UK. Study duration was previously defined as exactly 30 months in Substantial Amendment 3.0 and was prolonged to 36 months in this protocol amendment to satisfy MHRA request of better defining the study duration. |
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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 | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/24412910 |