A Phase 3 interventional study of Human Normal Immunoglobulin for Subcutaneous Administration in Primary Immune Deficiency, sponsored by CSL Behring. Completed at 13 sites in United States. Open to participants aged 2 Years to 75 Years. Per ClinicalTrials.gov, last updated 2013-01-25.
Sponsored by CSL Behring · Phase 3, Interventional, and Treatment
The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).
The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.
199 studies on the registry are indexed under Primary Immunodeficiency Diseases; 46 are open to participants now.
This study's enrollment of 49 is above the median of 37 across 121 interventional studies indexed under Primary Immunodeficiency Diseases.
Browse Primary Immunodeficiency Diseases studies →CSL Behring is the lead sponsor of 142 studies on the registry; 18 are open to participants now.
Of its 24 completed or terminated interventional studies of FDA-regulated products, 17 (71%) have results posted.
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Exclusion Criteria:
Human Normal Immunoglobulin for Subcutaneous Administration (IgPro20) is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator.
Biological: Human Normal Immunoglobulin for Subcutaneous Administration
Also known as: Hizentra
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/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 a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)
Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR \[NCT00168025\] or ZLB05_006CR \[NCT00322556\]).
Time frame: Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment
Annualized Rate of Clinically Documented SBIs (ITT Population)
The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Time frame: For the duration of the study, up to 15 months
Annualized Rate of Clinically Documented SBIs (PPE Population)
The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Infection Episodes
The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time frame: Efficacy period: up to 12 months (week 13 to completion visit)
Number of Infection Episodes (Serious and Non-serious)
Total number of infections for the specified analysis population
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily 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 (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Hospitalization Due to Infection
The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Number of Days of Hospitalization Due to Infections
Total number of days of hospitalization due to infections for the specified analysis population
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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: Efficacy period: up to 12 months (week 13 to the completion visit)
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: Every 4 weeks, throughout the 12-month efficacy period
Maximum Concentration (Cmax) of Total Serum IgG at Steady State
Time frame: Week 28 ± 1 week of the treatment period
Tmax at Steady State
Timepoint of maximum concentration (Cmax)
Time frame: Week 28 ± 1 week of the treatment period
Minimum Concentration (Cmin) of Total Serum IgG at Steady State
Time frame: Week 28 ± 1 week of the treatment period
Rate of All AEs by Relatedness and Seriousness
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.
Time frame: For the duration of the study, up to 15 months
Rate of Mild, Moderate, or Severe Local Reactions
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 injection site reaction, injection site bruising, infusion site scab, injection site cyst, injection site eczema, injection site irritation, injection site nodule, and injection site pain. 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 15 months
A total of 12 centers in the United States enrolled subjects for this study.
| Milestone | IgPro20 |
|---|---|
| Started | 49 |
| Completed | 38 |
| Not completed | 11 |
| Withdrew: Withdrawal by subject | 8 |
| Withdrew: Adverse event | 2 |
| Withdrew: Disqualifying laboratory results | 1 |
| Milestone | IgPro20 |
|---|---|
| Started | 38 |
| Completed | 28 |
| Not completed | 10 |
| Withdrew: Withdrawal by subject | 6 |
| Withdrew: Protocol violation | 1 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Non-compliance | 1 |
| Withdrew: Termination of study site | 1 |
The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/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 a review committee to determine if the event fulfilled the predefined criteria for SBIs.
| SBIs per subject year | IgPro20 |
|---|---|
| Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population) | 0.00 |
Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR \[NCT00168025\] or ZLB05_006CR \[NCT00322556\]).
| days*g/L | IgPro20 (PK Substudy) | IVIG (Privigen; Previous Study) |
|---|---|---|
| Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG) | 105.6 ± 31.56 | 103.2 ± 20.00 |
The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
| SBIs per subject year | IgPro20 |
|---|---|
| Annualized Rate of Clinically Documented SBIs (ITT Population) | 0.00 |
The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
| SBIs per subject year | IgPro20 |
|---|---|
| Annualized Rate of Clinically Documented SBIs (PPE Population) | 0.00 |
The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
| infection episodes per subject year | IgPro20 |
|---|---|
| Annualized Rate of Infection Episodes | 2.76 (2.235 to 3.370) |
Total number of infections for the specified analysis population
| infections | IgPro20 |
|---|---|
| Number of Infection Episodes (Serious and Non-serious) | 96 |
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 (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
| days per subject year | IgPro20 |
|---|---|
| Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections | 2.06 |
Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population
| days | IgPro20 |
|---|---|
| Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections | 71 |
The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
| days per subject year | IgPro20 |
|---|---|
| Annualized Rate of Hospitalization Due to Infection | 0.20 (0 to 7) |
Total number of days of hospitalization due to infections for the specified analysis population
| days | IgPro20 |
|---|---|
| Number of Days of Hospitalization Due to Infections | 7 |
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.
| days per subject year | IgPro20 |
|---|---|
| Use of Antibiotics for Infection Prophylaxis and Treatment | 48.52 |
The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
| g/L | IgPro20 |
|---|---|
| Total Serum IgG Trough Levels | 12.53 ± 3.21 |
| g/L | IgPro20 (PK Substudy) |
|---|---|
| Maximum Concentration (Cmax) of Total Serum IgG at Steady State | 16.16 ± 4.93 |
Timepoint of maximum concentration (Cmax)
| days | IgPro20 (PK Substudy) |
|---|---|
| Tmax at Steady State | 3.118 ± 1.7729 |
| g/L | IgPro20 (PK Substudy) |
|---|---|
| Minimum Concentration (Cmin) of Total Serum IgG at Steady State | 13.70 ± 4.39 |
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.
| AEs per infusion | IgPro20 |
|---|---|
| All | 0.773 |
| At least possibly related | 0.634 |
| Serious | 0.004 |
| At least possibly related and serious | 0 |
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 injection site reaction, injection site bruising, infusion site scab, injection site cyst, injection site eczema, injection site irritation, injection site nodule, and injection site pain. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.
| local reactions per infusion | IgPro20 |
|---|---|
| All | 0.592 |
| Mild | 0.553 |
| Moderate | 0.038 |
| Severe | 0.002 |
Collected over Approximately 15 months (including the 3 month wash in/wash out period and the 12 month efficacy period).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| IgPro20 | — | 7/49 (14.3%) | 49/49 (100%) |
| Event | IgPro20 |
|---|---|
| Chest painGeneral disorders | 2/49 |
| GastroenteritisInfections and infestations | 1/49 |
| Small intestinal obstructionGastrointestinal disorders | 1/49 |
| Tooth abscessInfections and infestations | 1/49 |
| CellulitisInfections and infestations | 1/49 |
| Urinary tract infectionInfections and infestations | 1/49 |
| Haemoglobin decreasedInvestigations | 1/49 |
| Musculoskeletal stiffnessMusculoskeletal and connective tissue disorders | 1/49 |
| Papillary thyroid cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/49 |
| Event | IgPro20 |
|---|---|
| Injection site reactionGeneral disorders | 49/49 |
| SinusitisInfections and infestations | 14/49 |
| HeadacheNervous system disorders | 13/49 |
| NasopharyngitisInfections and infestations | 11/49 |
| CoughRespiratory, thoracic and mediastinal disorders | 8/49 |
| DiarrhoeaGastrointestinal disorders | 7/49 |
| BronchitisInfections and infestations | 6/49 |
| FatigueGeneral disorders | 6/49 |
| Abdominal pain upperGastrointestinal disorders | 5/49 |
| Acute sinusitisInfections and infestations | 5/49 |
| Age Continuous(years) | IgPro20 |
|---|---|
| Mean | 34.4 ± 20.09 |
| Age, Customized(participants) | IgPro20 |
|---|---|
| 2 to < 12 years | 3 |
| 12 to < 16 years | 7 |
| 16 to < 65 years | 33 |
| ≥ 65 years | 6 |
| Sex: Female, Male(Participants) | IgPro20 |
|---|---|
| Female | 27 |
| Male | 22 |
| Race/Ethnicity, Customized(participants) | IgPro20 |
|---|---|
| Black or African American | 3 |
| White | 46 |
| Type of Primary Immunodeficiency(participants) | IgPro20 |
|---|---|
| Common variable immunodeficiency (CVID) | 46 ± 21.24 |
| X-linked agammaglobulinemia (XLA) | 3 |
This study is completed, as verified in Dec 2012. You cannot join it, but the record below documents what was studied.
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