Study of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, efficacy and Pharmacokinetics of Immune Globulin Intravenous (Human) GC5107 in subjects with Primary Humoral Immunodeficiency (PHID).

Detailed Description
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This was a prospective, open-label, single-arm, historically controlled, multicenter phase 3 study measuring the safety, efficacy and pharmacokinetics and tolerability of GC5107 in subjects with Primary Humoral Immunodeficiency disease (PHID). Subjects received intravenous infusions of the investigational product at the same dose and interval as used for their previous Immunoglobulin intravenous (IVIG) maintenance therapy. GC5107 was administered every 21 or 28 days for a period of 12 months.

Official Title
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An Open-Label, Single-Arm, Historically Controlled, Prospective, Multicenter Phase III Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency

Conditions
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Immunologic Deficiency Syndromes

Intervention / Treatment
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* Biological: GC5107


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with a confirmed clinical diagnosis of a Primary Humoral Immunodeficiency Disease as defined by IUIS (International Union of Immunological Societies) and require treatment with IGIV. Documented agammaglobulinemia or hypogammaglobulinemia Male or Female, ages 2 to 70 years The subject has received 300-900 mg/kg of a licensed IGIV therapy at 21 or 28 day intervals for at least 3 months prior to this study At least 2 documented IgG trough levels of ≥ 500 mg/dL are obtained at two infusion cycles (21 or 28 days) within 12 months prior to study enrollment Exclusion Criteria: Subject has secondary immunodeficiency Subject was newly diagnosed with PHID and has not yet been treated with immunoglobulin Subject has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency or isolated IgA deficiency with known anti-IgA antibodies History of severe reaction or hypersensitivity to IGIV or other injectable form of IgG Subject has a lifetime history of at least one thrombotic event including deep vein thrombosis, cerebrovascular accident, pulmonary embolism, transient ischemic attacks, or myocardial infarction Subject has received blood products other than human albumin or human immunoglobulin within 12 months prior to enrollment

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 70 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: GC5107<br>GC5107 Immune globulin intravenous (human) solution, 10% liquid | Biological: GC5107<br>* GC5107 20g/200mL, intravenously, dose of 300 - 900 mg/kg (of body weight) every 21 or 28 days for 12 months, a follow-up (3 or 4 weeks)<br>* Other names: Immune globulin intravenous (human) solution, 10% liquid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Acute Serious Bacterial Infections (SBI) | The incidence of acute serious bacterial infections (aSBIs) meeting FDA guidance criteria, which includes bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscesses, and osteomyelitis/septic arthritis. Efficacy data is evaluated by comparing the frequency of acute serious bacterial infections per subject per year according to the FDA guideline of an upper one-sided 99% confidence limit < 1.0 per subject per year. | One year | 
| The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product | The proportion of infusions with temporally associated adverse events occurring during or within 72 hours following infusion, whether or not they were thought to be related to GC5107 | Within 72 hours after an infusion of GC5107 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Infections Other Than Acute Serious Bacterial Infections |  | One year | 
| The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections | Based on the total number of days missed from work/school/kindergarten/daycare or days unable to perform normal daily activities due to infections for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. | One year | 
| The Number of Days of Unscheduled Physician Visits Due to Infections | Based on the total number of days of unscheduled physician visits due to infections for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. | One year | 
| The Number of Days of Hospitalizations Due to Infections | Subject with no experience of specific event will be included in the analysis as zero incidence, zero day, or zero time duration. The mean and SD will be calculated weighting for the duration of data available for each subject. | One year | 
| The Number of Days of Intravenous (IV) Therapeutic Antibiotics | Based on the total number of days of IV therapeutic antibiotics for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit -first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. | One year | 
| The Number of Days of Oral Therapeutic Antibiotics | Based on the total number of days of oral (PO) therapeutic antibiotics for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. | One year |