Extension Study of Subcutaneous Immunoglobulin Human in Patients With Primary Immunodeficiency (PID)

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter Extension Study of the Efficacy, Tolerability, and Safety of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency (PID)

Conditions
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Primary Immune Deficiency

Intervention / Treatment
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* Biological: IgPro20


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IgPro20<br>The IgPro20 dose will be the same as in the previous pivotal study ZLB04_009CR (NCT00419341) infused subcutaneously weekly or twice a week (in the latter case, half of a weekly dose will be used) | Biological: IgPro20<br> <br> * Other names: IgG with Proline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | For the duration of the study, up to approximately 104 weeks | 
| 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. | For the duration of the study, up to approximately 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | For the duration of the study, up to approximately 104 weeks | 
| Trough Levels of Total Immunoglobulin G (IgG) Serum Concentrations | Mean of individual median total IgG trough concentration. | Before infusion at Weeks 1, 24, 48, 72, and 96 | 
| 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 | 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. | For the duration of the study, up to approximately 104 weeks | 
| 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 | 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. | For the duration of the study, up to approximately 104 weeks | 
| Use of Antibiotics for Infection Prophylaxis and Treatment | Annualized rate of days with antibiotics for infection prophylaxis and treatment. | For the duration of the study, up to approximately 104 weeks | 
| 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. | For the duration of the study, up to approximately 104 weeks | 
| 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. | For the duration of the study, up to approximately 104 weeks | 
| 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. | Within 24 or 72 hours after each infusion | 
| 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. | Within 24 or 72 hours after each infusion | 
| 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. | For the duration of the study, up to approximately 104 weeks | 
| 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. | At weeks 1, 12, 24, 36, 48, 60, 72, 84, and 96 | 
| 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. | At Week 1, and study completion (approximately 104 weeks) | 
| 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. | At Week 1, and study completion (approximately 104 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CVID, XLA