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

Phase 3

Completed

• Conditions: Primary Immune Deficiency
• Interventions: Biological: Human Normal Immunoglobulin for Subcutaneous Administration

• Registration Number: NCT00419341
• Lead Sponsor: CSL Behring

Brief Summary

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

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.

Study Timeline

• Study Start: 2006-11
• Study First Submitted: 2006-12-22
• Study First Submitted QC: 2007-01-05
• Study First Posted: 2007-01-08
• Primary Completion: 2008-10
• Study Completion: 2008-10
• Status Verified: 2012-12
• Results First Submitted: 2012-12-16
• Results First Submitted QC: 2012-12-16
• Last Update Submitted: 2012-12-16
• Results First Posted: 2013-01-25
• Last Update Posted: 2013-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IgPro20	Human Normal Immunoglobulin for Subcutaneous Administration	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.

Primary Outcome Measures

Name	Time	Method
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)	Efficacy period: up to 12 months (week 13 to the completion visit)	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.
Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)	Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment	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 \[NCT00322556\]).

Secondary Outcome Measures

Name	Time	Method
Annualized Rate of Clinically Documented SBIs (ITT Population)	For the duration of the study, up to 15 months	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.
Annualized Rate of Clinically Documented SBIs (PPE Population)	Efficacy period: up to 12 months (week 13 to the completion visit)	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.
Annualized Rate of Infection Episodes	Efficacy period: up to 12 months (week 13 to completion visit)	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.
Number of Infection Episodes (Serious and Non-serious)	Efficacy period: up to 12 months (week 13 to the completion visit)	Total number of infections for the specified analysis population
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections	Efficacy period: up to 12 months (week 13 to the completion visit)	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.
Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections	Efficacy period: up to 12 months (week 13 to the completion visit)	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
Annualized Rate of Hospitalization Due to Infection	Efficacy period: up to 12 months (week 13 to the completion visit)	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.
Number of Days of Hospitalization Due to Infections	Efficacy period: up to 12 months (week 13 to the completion visit)	Total number of days of hospitalization due to infections for the specified analysis population
Use of Antibiotics for Infection Prophylaxis and Treatment	Efficacy period: up to 12 months (week 13 to the completion visit)	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.
Total Serum IgG Trough Levels	Every 4 weeks, throughout the 12-month efficacy period	The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
Maximum Concentration (Cmax) of Total Serum IgG at Steady State	Week 28 ± 1 week of the treatment period
Tmax at Steady State	Week 28 ± 1 week of the treatment period	Timepoint of maximum concentration (Cmax)

Trial Locations

Locations (1)

Study Site; 🇺🇸 Dallas, Texas, United States