Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy (EU Extension Study)

Study Overview
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Brief Summary
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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.

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 (IgPro20 EU Extension Study)

Conditions
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Primary Immunodeficiency (PID)

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, 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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 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>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). | Biological: IgPro20<br> <br> * Other names: Hizentra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 42 months | 
| 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. | Up to 42 months | 
| Number of Infection Episodes | Total number of infections for the specified analysis population | Up to 42 months | 
| 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. | Up to 42 months | 
| 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 | Up to 42 months | 
| 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. | Up to 42 months | 
| Number of Days of Hospitalization Due to Infections | Total number of days of hospitalization due to infections for the specified analysis population | Up to 42 months | 
| 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. | Up to 42 months | 
| 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. | At baseline and at the last available post-baseline observation for each subject (up to 42 months) | 
| 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. | At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months). | 
| 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. | At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months). | 
| 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. | Up to 42 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune globulin subcutaneous, SCIG, primary immunodeficiency, PID