Follow-up Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy (Japan Study)

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

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).

Study Overview

• Status: Completed
• Conditions: Primary Immune Deficiency Disorder
• Intervention / Treatment: Biological: Immune globulin subcutaneous (Human)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi Pref.
    • Nagoya city, Aichi Pref., Japan, 466-8560
      • Study Site
  • Chiba Pref.
    • Chiba city, Chiba Pref., Japan, 260-8677
      • Study Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Study Site
  • Gifu Pref.
    • Gifu city, Gifu Pref., Japan, 502-8558
      • Study Site
  • Hokkaido
    • Sapporo city, Hokkaido, Japan, 060-8648
      • Study Site
  • Osaka
    • Moriguchi city, Osaka, Japan, 570-8507
      • Study Site
  • Saitama Pref.
    • Koshigaya city, Saitama Pref., Japan, 343-8555
      • Study Site
    • Tokorozawa city, Saitama Pref., Japan, 359-8513
      • Study Site
  • Tokyo Metropolitan
    • Bunkyo-ku, Tokyo Metropolitan, Japan, 113-8519
      • Study Site

Participation Criteria

Eligibility Criteria

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

Description

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.

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	Biological: Immune globulin subcutaneous (Human); 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).; Other Names: Hizentra

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Infection Episodes (Serious and Non-serious)	The annualized rate of infection episodes (serious and non-serious) was based on the total number of infection episodes and the total number of subject study days for all subjects in the FAS population and the PPS population and adjusted to 365 days.	24 weeks

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Midori Kobayashi, CSL Behring K.K.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: October 12, 2011
• First Submitted That Met QC Criteria: October 21, 2011
• First Posted (Estimate): October 24, 2011

Study Record Updates

• Last Update Posted (Estimate): April 9, 2013
• Last Update Submitted That Met QC Criteria: February 27, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Immune globulin subcutaneous; SCIG; Primary immunodeficiency; PID
• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: ZLB07_001CR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No