Follow-up 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 long-term safety, tolerability, and efficacy of IgPro20 in subjects with primary immunodeficiency (PID) as a follow-up to the pivotal study ZLB06_002CR (NCT01199705).

Official Title
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A Multicenter Follow-up Study of Long-term Safety, Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency

Conditions
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Primary Immune Deficiency Disorder

Intervention / Treatment
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* Biological: Immune globulin subcutaneous (Human)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have participated in study ZLB06_002CR and who have tolerated IgPro20 well. Written informed consent by the subject/parent/legally acceptable representative. Written assent for an underage subject (≥7 years at the time of obtaining informed consent), as far as possible. Exclusion Criteria: Ongoing serious bacterial infections (SBIs) (pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess) at the time of the first infusion. Hypoalbuminemia, protein-losing enteropathies, and any proteinuria (known total urine protein concentration >0.2 g/L or urine protein ++ by dipstick). Pregnancy or nursing mother. Participation in a study with an investigational medicinal product (IMP) within 3 months prior to enrollment except for ZLB06_002CR. Subjects who are planning to donate blood during the study. Re-entry of subjects previously participating in the current follow-up study. Known or suspected antibodies to the IMP, or to excipients of the IMP.

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)<br>* IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human immunoglobulin for subcutaneous (SC) use. Subjects will receive weekly infusions of IgPro20 for a total of 24 weeks at a dose based on the subject's IgPro20 dose in the pivotal study ZLB06_002CR (NCT01199705).<br>* Other names: Hizentra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median of the Individual Subject's Rate of Adverse Events (AEs) Per Infusion | The rate was calculated by counting all newly developed or worsened AEs within a subject and dividing by the total number of IgPro20 infusions administered to this subject. Subsequently, the median of these individual AE rates per infusion was calculated. AE rates were classified (i) by severity (mild, moderate, severe) and (ii) by causal relationship to study medication (not related or unlikely related; at least possibly related [i.e., possibly related, probably related, or related]). | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Rate of AEs Per Infusion | The rate was calculated by counting all newly developed or worsened AEs during the treatment period in all subjects and dividing the total number of AEs by the total number of IgPro20 infusions administered. In addition, individual AEs were classified (i) by severity (mild, moderate, severe) and (ii) by causal relationship to study medication (not related or unlikely related; at least possibly related [i.e., possibly related, probably related, or related]). The AE rates per infusion by severity and causal relationship to study medication were calculated by dividing the number of AEs in each category by the total number of IgPro20 infusions. | 24 weeks | 
| Number of Subjects With Newly Developing or Worsening AEs | Number of subjects with AEs, overall and classified (i) by severity (mild, moderate, severe) and (ii) by causal relationship to study medication (not related or unlikely related; at least possibly related [i.e., possibly related, probably related, or related]). | 24 weeks | 
| Percentage of Infusions With Subject-assessed Tolerability of at Least 'Good' | Subjects assessed their overall perception of local tolerability at the infusion site throughout the study in the subject diary within a time window of 24 h to 72 h after the end of the latest infusion by assessing it as very good, good, fair, or poor. The reported percentage represents the percentage of subjects with local tolerability assessments of very good or good at any given study infusion. | 24 to 72 hours after infusion | 
| IgG Trough Level | Serum IgG trough levels at the completion visit compared to the baseline visit of the follow-up study. IgG trough levels at baseline, at the completion visit, and the change from baseline to the completion visit are shown | 24 weeks | 
| Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) | SBIs are defined as bacterial pneumonia, bacteremia and septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess. The annualized rate was based on the total number of SBIs and the total number of subject study days for all subjects in the FAS and PPS and adjusted to 365 days. | 24 weeks | 
| Number of Infection Episodes (Serious and Non-serious) |  | 24 weeks | 
| Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections. | Median number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections. | 24 weeks | 
| Number of Days of Hospitalization Due to Infections. | Median number of days of hospitalization due to infections. | 24 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 | 24 weeks | 

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