Primary Immunodeficiency (PID)
Conditions
Keywords
Immune globulin subcutaneous, SCIG, primary immunodeficiency, PID
Brief summary
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.
Interventions
BIOLOGICALIgPro20
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common variable immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and the European Society for Immunodeficiencies (ESID), or X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or autosomal recessive agammaglobulinemia who have participated in the study ZLB06\_001CR and who have tolerated IgPro well * Written informed consent
Exclusion criteria
* Hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined as total urine protein concentration \> 0.2g/L) * Other significant medical conditions that could increase the risk to the subject * Females who are pregnant, breast feeding or planning a pregnancy during the course of the study * Participation in a study with an investigational medicinal product within three months prior to enrollment, except for ZLB06\_001CR * Evidence of uncooperative attitude * Any condition that is likely to interfere with evaluation of the IMP or satisfactory conduct of the study * Subjects who are employees at the investigational site, relatives or spouse of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Serum IgG Trough Levels | Up to 42 months | The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) | Up to 42 months | 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. |
| Annualized Rate of Infection Episodes | Up to 42 months | 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. |
| Number of Infection Episodes | Up to 42 months | Total number of infections for the specified analysis population |
| Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections | Up to 42 months | 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 specified analysis population and adjusted to 365 days. |
| Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections | Up to 42 months | Total number of days out of work / school / kindergarten / day care or unable to perform normal activities due to infections, for the specified analysis population |
| Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit. | At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months). | 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. |
| Number of Days of Hospitalization Due to Infections | Up to 42 months | Total number of days of hospitalization due to infections for the specified analysis population |
| Use of Antibiotics for Infection Prophylaxis and Treatment | Up to 42 months | 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 specified analysis population, and adjusted to 365 days. |
| Health Related Quality of Life (Short Form 36 Health Survey) | At baseline and at the last available post-baseline observation for each subject (up to 42 months) | The Short Form 36 Health Survey (SF-36) 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. |
| Clinically Relevant Changes in Vital Signs From Baseline to the Completion Visit. | At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months). | 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. |
| Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | Up to 42 months | 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. |
| Annualized Rate of Hospitalization Due to Infections | Up to 42 months | 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. |
Countries
France, Germany, Poland, Romania, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Recruitment details
Subjects who had previously participated in the pivotal study ZLB06\_001CR (NCT00542997) were enrolled in the extension study ZLB07\_002CR.
Participants by arm
| Arm | Count |
|---|---|
| IgPro20 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 (NCT00542997). | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Poor adherence to asthma treatment | 1 |
| Overall Study | Subject moved to another country | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | IgPro20 |
|---|---|
| Age, Customized 12 to < 16 years | 4 participants |
| Age, Customized 16 to < 65 years | 21 participants |
| Age, Customized 2 to < 12 years | 15 participants |
| Age, Customized ≥ 65 years | 0 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 40 |
| serious Total, serious adverse events | 14 / 40 |
Outcome results
Primary
Total Serum IgG Trough Levels
The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
Time frame: Up to 42 months
Population: The all treated (AT) safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the Full Analysis/intention-to-treat (ITT) data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 | Total Serum IgG Trough Levels | 7.97 g/L | Standard Deviation 1.171 |
Secondary
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs)
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.
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) | Annualized Rate | 0.048 SBIs per subject year |
| IgPro20 | Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) | Upper 1-sided 99% Confidence Limit | 0.1252 SBIs per subject year |
Secondary
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
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 specified analysis population and adjusted to 365 days.
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections | 6.773 days per subject year |
Secondary
Annualized Rate of Hospitalization Due to Infections
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.
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Hospitalization Due to Infections | 1.055 days per subject year |
Secondary
Annualized Rate of Infection Episodes
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.
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Infection Episodes | 3.334 infection episodes per subject year |
Secondary
Clinically Relevant Changes in Vital Signs From Baseline to the Completion Visit.
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.
Time frame: At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months).
Population: The AT safety data set (which comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available) and for whom vital signs data was collected at both baseline and completion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Clinically Relevant Changes in Vital Signs From Baseline to the Completion Visit. | 0 participants |
Secondary
Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit.
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.
Time frame: At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months).
Population: The AT safety data set (which comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available) and for whom laboratory parameter data was collected at both baseline and completion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit. | Haematology | 3 participants |
| IgPro20 | Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit. | Serum Chemistry | 1 participants |
| IgPro20 | Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit. | Urinalysis | 0 participants |
Secondary
Health Related Quality of Life (Short Form 36 Health Survey)
The Short Form 36 Health Survey (SF-36) 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.
Time frame: At baseline and at the last available post-baseline observation for each subject (up to 42 months)
Population: The analysis population comprised 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | Physical Functioning | 95.0 score on a scale |
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | Role-physical | 100.0 score on a scale |
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | Role-emotional | 100.0 score on a scale |
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | Social Functioning | 100.0 score on a scale |
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | Bodily Pain | 84.0 score on a scale |
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | Mental Health | 85.0 score on a scale |
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | Vitality | 65.6 score on a scale |
| IgPro20 | Health Related Quality of Life (Short Form 36 Health Survey) | General Health | 52.0 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | General Health | 54.5 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | Physical Functioning | 100.0 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | Bodily Pain | 84.0 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | Role-physical | 100.0 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | Vitality | 75.0 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | Role-emotional | 100.0 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | Mental Health | 80.0 score on a scale |
| IgPro20 - At End of Study | Health Related Quality of Life (Short Form 36 Health Survey) | Social Functioning | 100.0 score on a scale |
Secondary
Number of Days of Hospitalization Due to Infections
Total number of days of hospitalization due to infections for the specified analysis population
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Days of Hospitalization Due to Infections | 110 days |
Secondary
Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
Total number of days out of work / school / kindergarten / day care or unable to perform normal activities due to infections, for the specified analysis population
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections | 706 days |
Secondary
Number of Infection Episodes
Total number of infections for the specified analysis population
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Infection Episodes | 349 infection episodes |
Secondary
Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion
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.
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | Total AEs | 0.0936 AEs per infusion |
| IgPro20 | Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | Mild AEs | 0.0685 AEs per infusion |
| IgPro20 | Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | Moderate AEs | 0.0231 AEs per infusion |
| IgPro20 | Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | Severe AEs | 0.0020 AEs per infusion |
| IgPro20 | Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | At least possibly related AEs | 0.0026 AEs per infusion |
| IgPro20 | Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | Serious AEs | 0.0033 AEs per infusion |
| IgPro20 | Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion | At least possibly related and serious AEs | 0 AEs per infusion |
Secondary
Use of Antibiotics for Infection Prophylaxis and Treatment
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 specified analysis population, and adjusted to 365 days.
Time frame: Up to 42 months
Population: The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Use of Antibiotics for Infection Prophylaxis and Treatment | 72.13 days per subject year |