Primary Immune Deficiency
Conditions
Keywords
CVID, XLA
Brief summary
The purpose of this study is to determine whether a long-term use of a new human immunoglobulin G with proline (IgPro) is safe and effective in the treatment of primary immunodeficiency.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with primary humoral immunodeficiency who have participated in the study ZLB04\_009CR (NCT00419341), namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or X-linked Agammaglobulinemia (XLA) as defined by PAGID and ESID * Women of childbearing potential must be using and agree to continue using medically approved contraception and must have a negative pregnancy test at screening * Written informed consent
Exclusion criteria
* Ongoing serious bacterial infection at the time of screening * Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma, and immunodeficiency with thymoma * Hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration \> 0.2 g/L) * Other significant medical conditions that could increase the risk to the patient * Females who are pregnant, breast-feeding or planning a pregnancy during the course of the study * A positive result at screening on any of the following viral markers: Human immunodeficiency virus (HIV), Hepatitis C virus (HCV) or Hepatitis B virus (HBV) * Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration \> 2.5 times Upper Normal Limit (UNL) at Completion Visit of study ZLB04\_009CR (NCT00419341) * Creatinine concentration \> 1.5 times UNL at Completion Visit of study ZLB04\_009CR (NCT00419341) * Participation in a study with an investigational product other than IgPro20 within 3 months prior to enrollment * Evidence of uncooperative attitude * Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial * Subjects who are employees at the investigational site, relatives or spouse of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Serious Bacterial Infection (Intention-to-Treat Population) | For the duration of the study, up to approximately 104 weeks | 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. |
| Annualized Rate of Serious Bacterial Infection (Per-Protocol Efficacy Population) | For the duration of the study, up to approximately 104 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection | For the duration of the study, up to approximately 104 weeks | — |
| Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection | For the duration of the study, up to approximately 104 weeks | 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 study days for all subjects in the specified analysis population and adjusted to 365 days. |
| Number of Days of Hospitalization Due to Infection | For the duration of the study, up to approximately 104 weeks | — |
| Annualized Rate of Hospitalization Due to Infection | For the duration of the study, up to approximately 104 weeks | The annualized rate was based on the total number of days of hospitalization due to infection and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. |
| Use of Antibiotics for Infection Prophylaxis and Treatment | For the duration of the study, up to approximately 104 weeks | Annualized rate of days with antibiotics for infection prophylaxis and treatment. |
| Rate of All AEs by Relatedness and Severity | For the duration of the study, up to approximately 104 weeks | The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. |
| Annualized Rate of Any Infection | For the duration of the study, up to approximately 104 weeks | 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. |
| Number of Subjects With Any Temporally Associated Adverse Event (AE) Within 24 or 72 Hours After an Infusion | Within 24 or 72 hours after each infusion | AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion. |
| Rate of Temporally Associated AEs Within 24 or 72 Hours of an Infusion | Within 24 or 72 hours after each infusion | The rate of AEs was the number of AEs over the number of infusions administered. AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion. |
| Number of Subjects Reporting Mild, Moderate, or Severe Local AEs | For the duration of the study, up to approximately 104 weeks | In addition to the standard MedDRA System Organ Class (SOC) AE assignments, the category of 'local reactions' was defined to provide the possibility for a combined analysis of local reactions and included AEs of infusion site oedema, infusion site reaction, injection site pain, injection site rash, and injection site reaction. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. |
| Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Vital Signs | At weeks 1, 12, 24, 36, 48, 60, 72, 84, and 96 | Vital signs included blood pressure (systolic and diastolic), heart rate, and body temperature. |
| Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Routine Laboratory Parameters | At Week 1, and study completion (approximately 104 weeks) | Routine laboratory parameters included hematology, blood chemistry, and urinalysis parameters. |
| Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Viral Safety Markers | At Week 1, and study completion (approximately 104 weeks) | Viral safety markers included human immunodeficiency virus (HIV)-1, HIV-2, hepatitis A virus (HAV), HBV, HCV, and parvovirus B19. |
| Relatedness and Severity of All AEs (Percentage of Total AEs) | For the duration of the study, up to approximately 104 weeks | At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. |
| Trough Levels of Total Immunoglobulin G (IgG) Serum Concentrations | Before infusion at Weeks 1, 24, 48, 72, and 96 | Mean of individual median total IgG trough concentration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IgPro20 A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | IgPro20 |
|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 18.53 |
| Age, Customized >= 12 to < 16 years | 1 participants |
| Age, Customized >= 16 to < 65 years | 16 participants |
| Age, Customized >= 2 to < 12 years | 1 participants |
| Age, Customized >= 65 years | 3 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 4 / 21 |
Outcome results
Primary
Annualized Rate of Serious Bacterial Infection (Intention-to-Treat Population)
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.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The Intention-to-Treat (ITT) population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Serious Bacterial Infection (Intention-to-Treat Population) | 0.06 infections per subject year |
Primary
Annualized Rate of Serious Bacterial Infection (Per-Protocol Efficacy Population)
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.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The Per-Protocol Efficacy population comprised all subjects who completed at least 48 weeks of the efficacy period that started with the first IgPro20 dose in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Serious Bacterial Infection (Per-Protocol Efficacy Population) | 0.03 infections per subject year |
Secondary
Annualized Rate of Any Infection
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.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The ITT population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Any Infection | 2.38 infections per subject year |
Secondary
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection
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 study days for all subjects in the specified analysis population and adjusted to 365 days.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The ITT population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection | 4.28 days per subject year |
Secondary
Annualized Rate of Hospitalization Due to Infection
The annualized rate was based on the total number of days of hospitalization due to infection and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The ITT population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Annualized Rate of Hospitalization Due to Infection | 0.55 days per subject year |
Secondary
Number of Days of Hospitalization Due to Infection
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The ITT population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 | Number of Days of Hospitalization Due to Infection | 0.857 days | Standard Deviation 2.726 |
Secondary
Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The ITT population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 | Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection | 6.67 days | Standard Deviation 13.49 |
Secondary
Number of Subjects Reporting Mild, Moderate, or Severe Local AEs
In addition to the standard MedDRA System Organ Class (SOC) AE assignments, the category of 'local reactions' was defined to provide the possibility for a combined analysis of local reactions and included AEs of infusion site oedema, infusion site reaction, injection site pain, injection site rash, and injection site reaction. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The AT safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Number of Subjects Reporting Mild, Moderate, or Severe Local AEs | Total | 19 participants |
| IgPro20 | Number of Subjects Reporting Mild, Moderate, or Severe Local AEs | Mild | 16 participants |
| IgPro20 | Number of Subjects Reporting Mild, Moderate, or Severe Local AEs | Moderate | 3 participants |
| IgPro20 | Number of Subjects Reporting Mild, Moderate, or Severe Local AEs | Severe | 0 participants |
Secondary
Number of Subjects With Any Temporally Associated Adverse Event (AE) Within 24 or 72 Hours After an Infusion
AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion.
Time frame: Within 24 or 72 hours after each infusion
Population: The AT safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Number of Subjects With Any Temporally Associated Adverse Event (AE) Within 24 or 72 Hours After an Infusion | AEs within 24 hours | 21 participants |
| IgPro20 | Number of Subjects With Any Temporally Associated Adverse Event (AE) Within 24 or 72 Hours After an Infusion | AEs within 72 hours | 21 participants |
Secondary
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Routine Laboratory Parameters
Routine laboratory parameters included hematology, blood chemistry, and urinalysis parameters.
Time frame: At Week 1, and study completion (approximately 104 weeks)
Population: The AT safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Routine Laboratory Parameters | 0 participants |
Secondary
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Viral Safety Markers
Viral safety markers included human immunodeficiency virus (HIV)-1, HIV-2, hepatitis A virus (HAV), HBV, HCV, and parvovirus B19.
Time frame: At Week 1, and study completion (approximately 104 weeks)
Population: The AT safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Viral Safety Markers | 0 participants |
Secondary
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Vital Signs
Vital signs included blood pressure (systolic and diastolic), heart rate, and body temperature.
Time frame: At weeks 1, 12, 24, 36, 48, 60, 72, 84, and 96
Population: The AT safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Vital Signs | 0 participants |
Secondary
Rate of All AEs by Relatedness and Severity
The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Rate of All AEs by Relatedness and Severity | All | 0.661 AEs per infusion |
| IgPro20 | Rate of All AEs by Relatedness and Severity | Unrelated | 0.137 AEs per infusion |
| IgPro20 | Rate of All AEs by Relatedness and Severity | At least possibly related | 0.524 AEs per infusion |
| IgPro20 | Rate of All AEs by Relatedness and Severity | Mild | 0.575 AEs per infusion |
| IgPro20 | Rate of All AEs by Relatedness and Severity | Moderate | 0.076 AEs per infusion |
| IgPro20 | Rate of All AEs by Relatedness and Severity | Severe | 0.010 AEs per infusion |
Secondary
Rate of Temporally Associated AEs Within 24 or 72 Hours of an Infusion
The rate of AEs was the number of AEs over the number of infusions administered. AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion.
Time frame: Within 24 or 72 hours after each infusion
Population: The AT safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Rate of Temporally Associated AEs Within 24 or 72 Hours of an Infusion | AEs within 24 hours | 0.322 AEs per infusion |
| IgPro20 | Rate of Temporally Associated AEs Within 24 or 72 Hours of an Infusion | AEs within 72 hours | 0.575 AEs per infusion |
Secondary
Relatedness and Severity of All AEs (Percentage of Total AEs)
At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The AT safety population comprised all subjects treated with the study medication during any study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IgPro20 | Relatedness and Severity of All AEs (Percentage of Total AEs) | Unrelated | 20.7 percentage of total AEs |
| IgPro20 | Relatedness and Severity of All AEs (Percentage of Total AEs) | At least possibly related | 79.3 percentage of total AEs |
| IgPro20 | Relatedness and Severity of All AEs (Percentage of Total AEs) | Mild | 87.0 percentage of total AEs |
| IgPro20 | Relatedness and Severity of All AEs (Percentage of Total AEs) | Moderate | 11.5 percentage of total AEs |
| IgPro20 | Relatedness and Severity of All AEs (Percentage of Total AEs) | Severe | 1.5 percentage of total AEs |
Secondary
Trough Levels of Total Immunoglobulin G (IgG) Serum Concentrations
Mean of individual median total IgG trough concentration.
Time frame: Before infusion at Weeks 1, 24, 48, 72, and 96
Population: The ITT population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IgPro20 | Trough Levels of Total Immunoglobulin G (IgG) Serum Concentrations | 11.98 g/L | Standard Deviation 3.65 |
Secondary
Use of Antibiotics for Infection Prophylaxis and Treatment
Annualized rate of days with antibiotics for infection prophylaxis and treatment.
Time frame: For the duration of the study, up to approximately 104 weeks
Population: The ITT population comprised all subjects treated with study medication during any study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IgPro20 | Use of Antibiotics for Infection Prophylaxis and Treatment | 83.87 days per subject year |