Extension Study of Subcutaneous Immunoglobulin Human in Patients With Primary Immunodeficiency (PID)

A Multicenter Extension Study of the Efficacy, Tolerability, and Safety of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency (PID)

The purpose of this study is to determine whether a long-term use of a new human immunoglobulin G with proline (IgPro) is safe and effective in the treatment of primary immunodeficiency.

Study Overview

• Status: Completed
• Conditions: Primary Immune Deficiency
• Intervention / Treatment: Biological: IgPro20

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Contact CSL Behring for facility details
  • Florida
    • North Palm Beach, Florida, United States, 33408
      • Contact CSL Behring for facility details
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Contact CSL Behring for facility details
  • Texas
    • Dallas, Texas, United States, 75230
      • Contact CSL Behring for facility details

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with primary humoral immunodeficiency who have participated in the study ZLB04_009CR (NCT00419341), namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or X-linked Agammaglobulinemia (XLA) as defined by PAGID and ESID
• Women of childbearing potential must be using and agree to continue using medically approved contraception and must have a negative pregnancy test at screening
• Written informed consent

Exclusion Criteria:

• 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
• Hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration > 0.2 g/L)
• Other significant medical conditions that could increase the risk to the patient
• Females who are pregnant, breast-feeding or planning a pregnancy during the course of the study
• A positive result at screening on any of the following viral markers: Human immunodeficiency virus (HIV), Hepatitis C virus (HCV) or Hepatitis B virus (HBV)
• Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration > 2.5 times Upper Normal Limit (UNL) at Completion Visit of study ZLB04_009CR (NCT00419341)
• Creatinine concentration > 1.5 times UNL at Completion Visit of study ZLB04_009CR (NCT00419341)
• Participation in a study with an investigational product other than IgPro20 within 3 months prior to enrollment
• Evidence of uncooperative attitude
• Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial
• Subjects who are employees at the investigational site, relatives or spouse of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IgPro20; The IgPro20 dose will be the same as in the previous pivotal study ZLB04_009CR (NCT00419341) infused subcutaneously weekly or twice a week (in the latter case, half of a weekly dose will be used)	Biological: IgPro20; Other Names: IgG with Proline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Rate of Serious Bacterial Infection (Intention-to-Treat Population)	The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. Acute serious bacterial infections included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess.	For the duration of the study, up to approximately 104 weeks
Annualized Rate of Serious Bacterial Infection (Per-Protocol Efficacy Population)	The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. Acute serious bacterial infections included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess.	For the duration of the study, up to approximately 104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Rate of Any Infection	The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.	For the duration of the study, up to approximately 104 weeks
Trough Levels of Total Immunoglobulin G (IgG) Serum Concentrations	Mean of individual median total IgG trough concentration.	Before infusion at Weeks 1, 24, 48, 72, and 96
Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection		For the duration of the study, up to approximately 104 weeks
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection	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, and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.	For the duration of the study, up to approximately 104 weeks
Number of Days of Hospitalization Due to Infection		For the duration of the study, up to approximately 104 weeks
Annualized Rate of Hospitalization Due to Infection	The annualized rate was based on the total number of days of hospitalization due to infection and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.	For the duration of the study, up to approximately 104 weeks
Use of Antibiotics for Infection Prophylaxis and Treatment	Annualized rate of days with antibiotics for infection prophylaxis and treatment.	For the duration of the study, up to approximately 104 weeks
Rate of All AEs by Relatedness and Severity	The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.	For the duration of the study, up to approximately 104 weeks
Relatedness and Severity of All AEs (Percentage of Total AEs)	At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.	For the duration of the study, up to approximately 104 weeks
Number of Subjects With Any Temporally Associated Adverse Event (AE) Within 24 or 72 Hours After an Infusion	AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion.	Within 24 or 72 hours after each infusion
Rate of Temporally Associated AEs Within 24 or 72 Hours of an Infusion	The rate of AEs was the number of AEs over the number of infusions administered. AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion.	Within 24 or 72 hours after each infusion
Number of Subjects Reporting Mild, Moderate, or Severe Local AEs	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 oedema, infusion site reaction, injection site pain, injection site rash, and injection site reaction. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.	For the duration of the study, up to approximately 104 weeks
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Vital Signs	Vital signs included blood pressure (systolic and diastolic), heart rate, and body temperature.	At weeks 1, 12, 24, 36, 48, 60, 72, 84, and 96
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Routine Laboratory Parameters	Routine laboratory parameters included hematology, blood chemistry, and urinalysis parameters.	At Week 1, and study completion (approximately 104 weeks)
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Viral Safety Markers	Viral safety markers included human immunodeficiency virus (HIV)-1, HIV-2, hepatitis A virus (HAV), HBV, HCV, and parvovirus B19.	At Week 1, and study completion (approximately 104 weeks)

Collaborators and Investigators

• Sponsor: CSL Behring

Publications and helpful links

General Publications

• Jolles S, Borte M, Nelson RP Jr, Rojavin M, Bexon M, Lawo JP, Wasserman RL. Long-term efficacy, safety, and tolerability of Hizentra(R) for treatment of primary immunodeficiency disease. Clin Immunol. 2014 Feb;150(2):161-9. doi: 10.1016/j.clim.2013.10.008. Epub 2013 Oct 26.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: July 21, 2008
• First Submitted That Met QC Criteria: July 21, 2008
• First Posted (Estimate): July 22, 2008

Study Record Updates

• Last Update Posted (Estimate): April 2, 2014
• Last Update Submitted That Met QC Criteria: March 5, 2014
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: CVID; XLA
• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
• Other Study ID Numbers: IgPro20_3001; 1473 (Other Identifier: CSL Behring)