Study of Subcutaneous Immune Globulin in Patients 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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This study consisted of a 12-week wash-in/wash-out period followed by a 28-week efficacy period. During the 28-week efficacy period, subjects visited the study site at least every 4 weeks for efficacy and safety evaluations and additionally recorded details regarding IgPro20 dose and certain aspects of efficacy and safety in a diary. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects during 1 treatment interval at steady-state (Week 28 ± 1).

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

Conditions
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Common Variable Immunodeficiency, X-linked Agammaglobulinemia, Autosomal Recessive Agammaglobulinemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or Autosomal Recessive Agammaglobulinemia Chest X-ray or CT scan obtained within 1 year prior to enrolment Exclusion Criteria: Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy Ongoing serious bacterial infection at the time of screening 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 associated with high anti-IgA Additional criteria may apply and examination by an investigator is required to determine eligibility.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IgPro20<br> | Biological: Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)<br>* 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.<br>* Other names: SCIG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Serum IgG Trough Levels | Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject's median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion. | Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population) | Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters. The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days. | Efficacy period: week 12 to week 40 after study start or to the completion visit | 
| Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population) | Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters. The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the PPE population and adjusted to 365 days. | Efficacy period: week 12 to week 40 after study start or to the completion visit | 
| Annual Rate of Infection Episodes | The annual rate of episodes was calculated based on the total number of any infection type and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days. | Efficacy period: week 12 to week 40 after study start or to the completion visit | 
| Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections | The annual rate was calculated based on the total number of days out of work/school/kindergarten/day care or unable to perform normal activities due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days. | Efficacy period: week 12 to week 40 after study start or to the completion visit | 
| Annual Rate of the Number of Days of Hospitalization Due to Infections | The annual rate was calculated based on the total number of days of hospitalization due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days. | Efficacy period: week 12 to week 40 after study start or to the completion visit | 
| Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment | The annual rate was calculated based on the total number of days of antibiotic use in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days. | Efficacy period: week 12 to week 40 after study start or to the completion visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subcutaneous immune globulin, SCIG