Primary Immune Deficiency Disorder
Conditions
Keywords
Immune globulin subcutaneous, SCIG, Primary immunodeficiency, PID
Brief summary
The objective of this study is 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 (NCT01199705).
Interventions
BIOLOGICALImmune 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 (NCT01199705).
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who have participated in study ZLB06\_002CR and who have tolerated IgPro20 well. * Written informed consent by the subject/parent/legally acceptable representative. Written assent for an underage subject (≥7 years at the time of obtaining informed consent), as far as possible.
Exclusion criteria
* Ongoing serious bacterial infections (SBIs) (pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess) at the time of the first infusion. * Hypoalbuminemia, protein-losing enteropathies, and any proteinuria (known total urine protein concentration \>0.2 g/L or urine protein ++ by dipstick). * Pregnancy or nursing mother. * Participation in a study with an investigational medicinal product (IMP) within 3 months prior to enrollment except for ZLB06\_002CR. * Subjects who are planning to donate blood during the study. * Re-entry of subjects previously participating in the current follow-up study. * Known or suspected antibodies to the IMP, or to excipients of the IMP.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | 24 weeks | 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 \[i.e., possibly related, probably related, or related\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Rate of AEs Per Infusion | 24 weeks | 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. |
| Number of Subjects With Newly Developing or Worsening AEs | 24 weeks | 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 \[i.e., possibly related, probably related, or related\]). |
| Percentage of Infusions With Subject-assessed Tolerability of at Least 'Good' | 24 to 72 hours after infusion | 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 percentage represents the percentage of subjects with local tolerability assessments of very good or good at any given study infusion. |
| IgG Trough Level | 24 weeks | 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 |
| Number of Infection Episodes (Serious and Non-serious) | 24 weeks | — |
| Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections. | 24 weeks | Median number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections. |
| Number of Days of Hospitalization Due to Infections. | 24 weeks | Median number of days of hospitalization due to infections. |
| Duration of Use of Antibiotics for Infection Prophylaxis and Treatment | 24 weeks | Median number of days of use of antibiotics for infection prophylaxis and/or treatment |
| Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) | 24 weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of Infection Episodes (Serious and Non-serious) | 24 weeks | 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. |
Countries
Japan
Participant flow
Recruitment details
This multicenter study enrolled subjects at nine study centers in Japan who had participated in the preceding pivotal study ZLB06\_002CR (CT.gov identifier: NCT01199705).
Pre-assignment details
Only subjects participating in the preceding pivotal study ZLB06\_002CR (NCT01199705) were eligible. The enrolment visit of this study was on the same day as the completion visit of the preceding pivotal study ZLB06\_002CR.
Participants by arm
| Arm | Count |
|---|---|
| IgPro20 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 (NCT01199705). | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | IgPro20 |
|---|---|
| Age Continuous | 20.8 years STANDARD_DEVIATION 13.68 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 23 |
| serious Total, serious adverse events | 1 / 23 |
Outcome results
Primary
Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion
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 \[i.e., possibly related, probably related, or related\]).
Time frame: 24 weeks
Population: The All Treated (AT) set comprised all subjects receiving at least 1 IgPro20 infusion.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IgPro20 | Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | All AEs | 0.167 AEs per infusion |
| IgPro20 | Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | Mild AEs | 0.125 AEs per infusion |
| IgPro20 | Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | Moderate AEs | 0 AEs per infusion |
| IgPro20 | Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | Severe AEs | 0 AEs per infusion |
| IgPro20 | Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | Not related or unlikely related AEs | 0.125 AEs per infusion |
| IgPro20 | Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | At least possibly related AEs | 0 AEs per infusion |
Secondary
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs)
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.
Time frame: 24 weeks
Population: The FAS comprised all subjects receiving at least 1 IgPro20 infusion. The 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) | 0.00 SBIs per subject year |
| IgPro20 - PPS | Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) | 0.00 SBIs per subject year |
Secondary
Duration of Use of Antibiotics for Infection Prophylaxis and Treatment
Median number of days of use of antibiotics for infection prophylaxis and/or treatment
Time frame: 24 weeks
Population: The FAS comprised all subjects receiving at least 1 IgPro20 infusion. The 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Duration of Use of Antibiotics for Infection Prophylaxis and Treatment | 91.5 days |
| IgPro20 - PPS | Duration of Use of Antibiotics for Infection Prophylaxis and Treatment | 154.0 days |
Secondary
IgG Trough Level
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
Time frame: 24 weeks
Population: The Full Analysis Set (FAS) comprised all subjects receiving at least 1 IgPro20 infusion. 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IgPro20 | IgG Trough Level | Baseline | 7.469 g/L | Standard Deviation 1.3943 |
| IgPro20 | IgG Trough Level | Completion visit | 8.914 g/L | Standard Deviation 4.0502 |
| IgPro20 | IgG Trough Level | Change from baseline to the completion vist | 1.445 g/L | Standard Deviation 3.4379 |
| IgPro20 - PPS | IgG Trough Level | Baseline | 7.586 g/L | Standard Deviation 1.3363 |
| IgPro20 - PPS | IgG Trough Level | Completion visit | 8.227 g/L | Standard Deviation 1.5458 |
| IgPro20 - PPS | IgG Trough Level | Change from baseline to the completion vist | 0.642 g/L | Standard Deviation 0.7687 |
Secondary
Number of Days of Hospitalization Due to Infections.
Median number of days of hospitalization due to infections.
Time frame: 24 weeks
Population: The FAS comprised all subjects receiving at least 1 IgPro20 infusion. The 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Number of Days of Hospitalization Due to Infections. | 0 days |
| IgPro20 - PPS | Number of Days of Hospitalization Due to Infections. | 0 days |
Secondary
Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections.
Median number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections.
Time frame: 24 weeks
Population: The FAS comprised all subjects receiving at least 1 IgPro20 infusion. The 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IgPro20 | Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections. | 0 days |
| IgPro20 - PPS | Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections. | 0 days |
Secondary
Number of Infection Episodes (Serious and Non-serious)
Time frame: 24 weeks
Population: The FAS comprised all subjects receiving at least 1 IgPro20 infusion. The 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Infection Episodes (Serious and Non-serious) | 43 infection episodes |
| IgPro20 - PPS | Number of Infection Episodes (Serious and Non-serious) | 38 infection episodes |
Secondary
Number of Subjects With Newly Developing or Worsening AEs
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 \[i.e., possibly related, probably related, or related\]).
Time frame: 24 weeks
Population: The AT set comprised all subjects receiving at least 1 IgPro20 infusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Number of Subjects With Newly Developing or Worsening AEs | At least possibly related | 10 participants |
| IgPro20 | Number of Subjects With Newly Developing or Worsening AEs | Severe AEs | 1 participants |
| IgPro20 | Number of Subjects With Newly Developing or Worsening AEs | All AEs | 22 participants |
| IgPro20 | Number of Subjects With Newly Developing or Worsening AEs | Mild AEs | 21 participants |
| IgPro20 | Number of Subjects With Newly Developing or Worsening AEs | Moderate AEs | 1 participants |
| IgPro20 | Number of Subjects With Newly Developing or Worsening AEs | Not related or unlikely related | 12 participants |
Secondary
Overall Rate of AEs Per Infusion
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.
Time frame: 24 weeks
Population: The AT set comprised all subjects receiving at least 1 IgPro20 infusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Overall Rate of AEs Per Infusion | All AEs | 0.346 AEs per infusion |
| IgPro20 | Overall Rate of AEs Per Infusion | Mild AEs | 0.342 AEs per infusion |
| IgPro20 | Overall Rate of AEs Per Infusion | Moderate AEs | 0.002 AEs per infusion |
| IgPro20 | Overall Rate of AEs Per Infusion | Severe AEs | 0.002 AEs per infusion |
| IgPro20 | Overall Rate of AEs Per Infusion | Not related or unlikely related AEs | 0.210 AEs per infusion |
| IgPro20 | Overall Rate of AEs Per Infusion | At least possibly related AEs | 0.136 AEs per infusion |
Secondary
Percentage of Infusions With Subject-assessed Tolerability of at Least 'Good'
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 percentage represents the percentage of subjects with local tolerability assessments of very good or good at any given study infusion.
Time frame: 24 to 72 hours after infusion
Population: The FAS comprised all subjects receiving at least 1 IgPro20 infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Percentage of Infusions With Subject-assessed Tolerability of at Least 'Good' | 85.4 percentage of infusions |
Other Pre-specified
Rate of Infection Episodes (Serious and Non-serious)
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.
Time frame: 24 weeks
Population: The FAS comprised all subjects receiving at least 1 IgPro20 infusion. The 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Rate of Infection Episodes (Serious and Non-serious) | 4.20 infection episodes per subject year |
| IgPro20 - PPS | Rate of Infection Episodes (Serious and Non-serious) | 4.32 infection episodes per subject year |