Study of Immune Globulin Intravenous (Human) GC5107 in Pediatric 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 pharmacokinetics and safety of Immune Globulin Intravenous (Human) GC5107 in pediatric subjects with Primary Humoral Immunodeficiency (PHID).

Detailed Description
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This is a prospective, open-label, single-arm, historically controlled, multi-center Phase III study to assess the pharmacokinetics and safety of Immune Globulin Intravenous (Human) GC5107 in pediatric subjects aged ≥ 2 years and < 17 years with PHID. Subjects will receive intravenous infusions of the investigational product at the same dose and interval as used for their previous Immunoglobulin intravenous (IGIV) maintenance therapy. GC5107 will be infused 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, Multi-Center Phase III Study to Evaluate the Pharmacokinetics and Safety of Immune Globulin Intravenous (Human) GC5107 in Pediatric Subjects With Primary Humoral Immunodeficiency

Conditions
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Primary Immune Deficiency

Intervention / Treatment
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* Biological: GC5107


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥ 2 to < 17 years of age, at the time of signing the informed consent Pediatric subject has a confirmed and documented clinical diagnosis of Primary Humoral Immunodeficiency, including hypogammaglobulinemia or agammaglobulinemia Subject who has received 300 - 900 mg/kg of IGIV therapy at 21 or 28 day intervals for at least 3 months prior to this study Subject who has at least 2 documented plasma IgG trough level of ≥ 500 mg/dL at two infusion cycles (21 or 28 days) within 12 months prior to enrollment Subject who is willing to comply with all requirements of the protocol Exclusion Criteria: Subject who has a history of clinically significant reactions or hypersensitivity to IGIV or other injectable forms of IgG Subject who has IgA deficiency and is known to have antibodies to IgA Subject who has secondary immunodeficiency Subject who has participated in another clinical study (other than an IGIV study) within 3 weeks prior to screening Subject who has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency or isolated IgA deficiency, or who has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator Subject who has received blood products other than human albumin or human immune globulin within 6 months prior to enrollment

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 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>Immune Globulin Intravenous (Human), 10% Liquid | Biological: GC5107<br>* Intravenously infused at a dose of 300 - 900 mg per kg (of body weight) every 21 or 28 days for 12 months<br>* Other names: Immune Globulin Intravenous (Human), 10% Liquid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Pharmacokinetic (PK) Plasma concentration-time curve of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Half-life of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Area under the curve of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Volume of distribution of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Maximum concentration of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Minimum concentration of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Time of maximum concentration of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Clearance of total IgG |  | before and after 5th infusion (12 or 16 weeks) | 
| Trough serum total IgG levels before each infusion of GC5107 in all subjects and the interval between infusions |  | 12 months | 
| The proportion of infusions with temporally associated adverse events (AEs) that occur during or within 1 hour, 24 hours, and 72 hours following an infusion of investigational product | AEs that occur during or within 1 hour, 24 hours, and 72 hours following each infusion during 12 months of the study period | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Pharmacokinetic (PK) Maximum concentration of IgG subclasses |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Minimum concentration of IgG subclasses |  | before and after 5th infusion (12 or 16 weeks) | 
| The Pharmacokinetic (PK) Half-life of IgG subclasses |  | before and after 5th infusion (12 or 16 weeks) | 
| Trough serum level of IgG subclasses and specific IgG antibodies before Infusion 1 and 13 (for subjects on 28-day infusion schedule) or Infusion 1 and 17 (for subjects on 21-day infusion schedule) |  | 12 months | 
| Number and proportion of subjects who failed to meet the target IgG trough level (500 mg/dL) at any time point equal to or subsequent to 5th infusion (estimated 5 half-lives) |  | 12 months | 
| The overall incidence of all AEs that occur during or within 1 hour, 24 hours, and 72 hours following an infusion of investigational product | AEs that occur during or within 1 hour, 24 hours, and 72 hours following each infusion during 12 months of the study period | 12 months | 
| The frequency of all AEs that occur during the study regardless of the investigator's assessment of their relationship to investigational product |  | 13 months (12 months of treatment + 1 month of follow-up) | 
| The frequency of suspected adverse reactions as defined by all AEs either classified as at least possibly related to GC5107 |  | 13 months (12 months of treatment + 1 month of follow-up) | 
| The number and proportion of GC5107 infusions for which the infusion rate was decreased due to AEs |  | 12 months | 
| The proportion of AEs considered by the investigator to be investigational product related |  | 13 months (12 months of treatment + 1 month of follow-up) | 
| Viral safety (freedom from transmission of blood-borne viral diseases): the human immunodeficiency virus (HIV) type 1 & 2, hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and parvovirus B19 |  | 13 months (12 months of treatment + 1 month of follow-up) |