Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy

Study Overview
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Brief Summary
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The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).

Detailed Description
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The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.

Official Title
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A Phase III Open-Label, Prospective, Multicenter Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human), IgPro20 in Subjects With Primary Immunodeficiency (PID)

Conditions
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Primary Immune Deficiency

Intervention / Treatment
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* Biological: Human Normal Immunoglobulin for Subcutaneous Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 2 to 75 years Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia) Written informed consent Exclusion Criteria: Newly diagnosed PID Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis) Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma Known hyperprolinemia Hypoalbuminemia, protein-losing enteropathies, and any proteinuria Allergic reactions to immunoglobulins or other blood products Known antibodies to Immunoglobulin A (IgA) The subject is receiving steroids (oral and parenteral, daily ≥ 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants Female who is pregnant, breast feeding or planning a pregnancy during the course of the study Participation in a study with an investigational product other than (IVIG) within 1 month prior to enrollment A positive result at screening on any of the following viral markers: Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV) Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration > 2.5 times the upper normal limit (UNL) Creatinine concentration > 1.5 times the UNL Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial

Ages Eligible for Study
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Minimum Age: 2 Years
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>Human Normal Immunoglobulin for Subcutaneous Administration (IgPro20) is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator. | Biological: Human Normal Immunoglobulin for Subcutaneous Administration<br> <br> * Other names: Hizentra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population) | The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs. | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG) | Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR [NCT00168025] or ZLB05_006CR [NCT00322556]). | Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate of Clinically Documented SBIs (ITT Population) | The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs. | For the duration of the study, up to 15 months | 
| Annualized Rate of Clinically Documented SBIs (PPE Population) | The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs. | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Annualized Rate of Infection Episodes | The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. | Efficacy period: up to 12 months (week 13 to completion visit) | 
| Number of Infection Episodes (Serious and Non-serious) | Total number of infections for the specified analysis population | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections | The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections | Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Annualized Rate of Hospitalization Due to Infection | The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Number of Days of Hospitalization Due to Infections | Total number of days of hospitalization due to infections for the specified analysis population | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Use of Antibiotics for Infection Prophylaxis and Treatment | Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days. | Efficacy period: up to 12 months (week 13 to the completion visit) | 
| Total Serum IgG Trough Levels | The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics. | Every 4 weeks, throughout the 12-month efficacy period | 
| Maximum Concentration (Cmax) of Total Serum IgG at Steady State |  | Week 28 ± 1 week of the treatment period | 
| Tmax at Steady State | Timepoint of maximum concentration (Cmax) | Week 28 ± 1 week of the treatment period | 

 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