Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)

Study Overview
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Brief Summary
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The objectives of this trial are the assessment of safety and efficacy of IgPro10 in patients with PID, and the assessment of tolerability of high infusion rates. To demonstrate safety, the number of infusions temporally associated with AEs, the rate, severity and relationship of all AEs and the vital sign changes during each infusion will be evaluated.

Official Title
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A Multicenter Extension Study on the Safety and Efficacy of IgPro10 in Patients With Primary Immunodeficiency (PID)

Conditions
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Agammaglobulinemia, IgG Deficiency, Common Variable Immunodeficiency

Intervention / Treatment
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* Drug: Immunoglobulins Intravenous (Human)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients with CVID (Common Variable Immunodeficiency) or XLA (X-linked agammaglobulinemia) who: Participated in the Phase III clinical study with intravenous IgPro10 (study number ZLB03_002CR) at 3- or 4- weekly intervals for 12 months (referred to as 'old' subjects) OR Were ≥ 6 years of age, were on other stable intravenous immunoglobulin therapy (200-800 mg IgG per kg body weight) at 3- or 4-week intervals for at least 6 months, AND were interested in participating in the Phase III clinical study with subcutaneous IgPro20 (study number ZLB04_009CR) (referred to as 'new' subjects) Written informed consent Key Exclusion Criteria: Diagnosis of epilepsia Insulin dependent diabetes Administration of steroids (daily ≥ 0.15 mg prednisone equivalent/kg/day) or other immunosuppressive drugs History of cardiac insufficiency (NYHA III/IV), cardiomyopathy, congestive heart failure, severe hypertension

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 71 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: IgPro10<br>See Intervention Description | Drug: Immunoglobulins Intravenous (Human)<br>* Liquid formulation; treatment schedule every 3 or 4 weeks using an individualized regimen with a dose of 0.2 - 0.8 g IgG per kg bw<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Infusions With One or More Temporally-associated Adverse Events (AEs). | AEs were considered temporally-associated AEs if they occurred during the infusion or in the period from the start of the infusion until either 48 or 72 hours after the end of the infusion. | During each infusion, and within 48 or 72 hours after the end of each infusion. | 
| Influence of Infusion Rate on Temporally-Associated AEs | The total and most frequent (1% or more) number of infusions for which subjects experienced temporally-associated AEs occurring within 72 hours of infusion, by infusion rate (≤ 4 mg/kg/min, ≤ 8 mg/kg/min, and > 8 and ≤ 12 mg/kg/min). AEs were considered to be temporally-associated AEs if they occurred in the period from the start of the infusion until 72 hours after the end of the infusion. | Within 72 hours after each infusion | 
| Rate of AEs by Severity and Relationship | The AE rate was the number of AEs over the number of infusions administered. Mild AEs: Did not interfere with daily activities; Moderate AEs: Interfered with routine daily activities; Severe AEs: Impossible to perform routine daily activities. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. | For the duration of the study, up to approximately 29 months | 
| Number of Subjects With Clinically Significant Changes in Vital Signs. | Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature. | Before, during, and after each infusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate of Acute Serious Bacterial Infections. | 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 29 months | 
| Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Illness. |  | For the duration of the study, up to approximately 29 months. | 
| Number of Days of Hospitalization. |  | For the duration of the study, up to approximately 29 months | 
| 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. Infections were classified as all AEs with the system organ class infections and infestations and AEs with the preferred term conjunctivitis. | For the duration of the study, up to approximately 29 months. | 
| Trough Levels of Total Immunoglobulin (IgG) Serum Concentrations. | Mean IgG trough concentration. For this analysis, each subject's values were first aggregated to their median and the median values were then analyzed. | Prior to each infusion; every 3 or 4 weeks depending upon the dosing schedule. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Immunoglobulin Intravenous, Agammaglobulinemia, Hypogammaglobulinemia, Common variable immunodeficiency, Immunoglobulin G