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

Study Overview
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Brief Summary
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The objective of this study is to assess the efficacy, safety, tolerability, and pharmacokinetics of a subcutaneous immune globulin (SCIG; IgPro20) in subjects with primary immunodeficiency (PID). In addition, the study will assess the health-related quality of life and pharmacoeconomic aspects related to treatment with IgPro20.

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

Conditions
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Primary Immune Deficiency

Intervention / Treatment
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* Biological: Immune Globulin Subcutaneous (Human) (SCIG)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PID with hypo- or agammaglobulinemia requiring IgG replacement therapy Intravenous IgG (IVIG) therapy at regular 3- or 4-week intervals at a stable dose for at least 3 doses prior to signing of informed consent Written informed consent Exclusion Criteria: Newly diagnosed PID, i.e., subjects who have not previously received immunoglobulin replacement therapy Ongoing serious bacterial infections (SBIs: pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess) at the time of screening Ongoing or history of concomitant malignancies of lymphoid cells such as lymphocytic leukemia, non-Hodgkin's lymphoma, and immunodeficiency with thymoma Allergic or other severe reactions to immunoglobulins or other blood products recorded in the past 3 months or at the time of screening Pregnancy or nursing mother A positive result at screening on any of the following viral markers: human immunodeficiency virus-1 (HIV-1), HIV-2, hepatitis C virus, or hepatitis B virus Participation in a study with other investigational product during this study and within 3 months prior to screening Subjects who donated blood (200 mL within one month or 400 mL within 3 months prior to screening), or planning to donate blood during the study

Ages Eligible for Study
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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> | Biological: Immune Globulin Subcutaneous (Human) (SCIG)<br>* IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human SCIG. Subjects will receive weekly infusions of IgPro20 at a weekly dosage calculated based on previous IVIG treatment.<br>* Other names: Hizentra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgG Trough Level | Geometric means of trough levels measured before 3 intravenous immunoglobulin (IVIG) infusions was compared with those of trough levels measured at steady-state for 3 subcutaneous immunoglobulin (SCIG) infusions (weeks 16, 20 and 24). The ratio of these geometric means was the primary outcome measure. | During IVIG period (IV 1, IV 2, IV 3) and during SCIG period at weeks 16, 20, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Infection Episodes (Serious and Non-serious) by Study Period | Number of infection episodes (serious and non-serious) presented by study period: IVIG treatment: Study subjects were treated with their IVIG therapy with 3- or 4-weekly schedules for 3 dosing cycles (9 to 12 weeks; before being switched to SCIG treatment with IgPro20). SCIG treatment (wash-in/wash-out; weeks 1 to 12): IgPro20 was administered subcutaneously with the first subcutaneous (SC) IgPro20 infusion starting 1 week after the last IVIG dose. Subjects were treated with weekly SC IgPro20 infusions for a 12-week wash-in/wash-out period. The IgPro20 dose was to be equal to the weekly equivalent dose of the previous IVIG therapy. SCIG treatment (efficacy; weeks 13 to 24): After the SCIG wash-in/wash-out treatment, subjects were treated with weekly SC IgPro20 infusions for a 12-week efficacy period. The IgPro20 dose was to be equal to the weekly equivalent dose of the previous IVIG therapy. | Up to 36 weeks | 
| Rate of Infection Episodes (Serious and Non-serious) by Study Period, PPS Population | The annualized rate of infection episodes (serious and non-serious) was based on the total number of infection episodes and the total number of subject study days for all subjects in the specified study periods (listed below) and analysis population and adjusted to 365 days. Study periods: IVIG treatment (up to 12 weeks) SCIG IgPro20 treatment (wash-in/wash-out period) (12 weeks) SCIG IgPro20 treatment (efficacy) (12 weeks) | Up to 36 weeks | 
| Rate of Infection Episodes (Serious and Non-serious) by Study Period, FAS Population | The annualized rate of infection episodes (serious and non-serious) was based on the total number of infection episodes and the total number of subject study days for all subjects in the specified study periods (listed below) and analysis population and adjusted to 365 days. Study periods: IVIG treatment (up to 12 weeks) SCIG IgPro20 treatment (wash-in/wash-out period) (12 weeks) SCIG IgPro20 treatment (efficacy) (12 weeks) | Up to 36 weeks | 
| Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections by Study Period | Median number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections, presented by study period: IVIG treatment (up to 12 weeks), SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks), and SCIG IgPro20 treatment (efficacy; 12 weeks). | Up to 36 weeks | 
| Number of Days of Hospitalization Due to Infections by Study Period | Median number of days of hospitalization due to infections, presented by study period: IVIG treatment (up to 12 weeks), SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks), and SCIG IgPro20 treatment (efficacy; 12 weeks). | Up to 36 weeks | 
| Duration of Use of Antibiotics for Infection Prophylaxis and Treatment | Median number of days of use of antibiotics for infection prophylaxis and/or treatment, presented by study period: IVIG treatment (up to 12 weeks), SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks), and SCIG IgPro20 treatment (efficacy; 12 weeks). | Up to 36 weeks | 
| Rate of All Adverse Events by Relatedness and Seriousness | The rate of adverse events (AEs) was the number of treatment-emergent AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. | For the duration of the study, up to 36 weeks | 
| Rate of Mild, Moderate, or Severe Local Reactions | 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 discomfort, infusion site erythema, infusion site haemorrhage, infusion site induration, infusion site inflammation, infusion site pain, infusion site pruritus, infusion site swelling, injection site erythema, injection site extravasation, injection site induration, injection site irritation, injection site pain, injection site pruritus, injection site swelling, and puncture site reaction. Mild AE: Symptoms are easily tolerated and there is no interference with daily activities; Moderate AE: Discomfort enough to cause some interference with daily activities; Severe AE: Incapacitating with inability to work or do usual activity. | For the duration of the study, up to 36 weeks | 

 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