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

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

The objective of this study is to assess the efficacy, safety, tolerability, and pharmacokinetics of a subcutaneous immune globulin (SCIG; IgPro20) in subjects with primary immunodeficiency (PID). In addition, the study will assess the health-related quality of life and pharmacoeconomic aspects related to treatment with IgPro20.

Study Overview

• Status: Completed
• Conditions: Primary Immune Deficiency
• Intervention / Treatment: Biological: Immune Globulin Subcutaneous (Human) (SCIG)

• Study Type: Interventional
• Enrollment (Actual): 25
• 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
  • Gifu Pref.
    • Gifu city, Gifu Pref., Japan, 501-1194
      • Study Site
  • Hokkaido
    • Sapporo city, Hokkaido, Japan, 060-8648
      • Study Site
  • Miyagi Pref.
    • Sendai city, Miyagi Pref., Japan, 980-8574
      • Study Site
  • Osaka
    • Fukuoka city, Osaka, Japan, 812-8582
      • Study Site
    • Moriguchi city, Osaka, Japan, 570-8507
      • Study Site
    • Osaka city, Osaka, Japan, 534-0021
      • Study Site
  • Saitama Pref.
    • Koshigaya city, Saitama Pref., Japan, 343-8555
      • Study Site
    • Tokorozawa city, Saitama Pref., Japan, 359-8513
      • 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:

• Diagnosis of PID with hypo- or agammaglobulinemia requiring IgG replacement therapy
• Intravenous IgG (IVIG) therapy at regular 3- or 4-week intervals at a stable dose for at least 3 doses prior to signing of informed consent
• Written informed consent

Exclusion Criteria:

• Newly diagnosed PID, i.e., subjects who have not previously received immunoglobulin replacement therapy
• Ongoing serious bacterial infections (SBIs: pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess) at the time of screening
• Ongoing or history of concomitant 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 recorded in the past 3 months or at the time of screening
• Pregnancy or nursing mother
• A positive result at screening on any of the following viral markers: human immunodeficiency virus-1 (HIV-1), HIV-2, hepatitis C virus, or hepatitis B virus
• Participation in a study with other investigational product during this study and within 3 months prior to screening
• Subjects who donated blood (200 mL within one month or 400 mL within 3 months prior to screening), or planning to donate blood during the study

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) (SCIG); IgPro20 is a 20% (weight per volume [w/v]) liquid formulation of human SCIG. Subjects will receive weekly infusions of IgPro20 at a weekly dosage calculated based on previous IVIG treatment.; Other Names: Hizentra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IgG Trough Level	Geometric means of trough levels measured before 3 intravenous immunoglobulin (IVIG) infusions was compared with those of trough levels measured at steady-state for 3 subcutaneous immunoglobulin (SCIG) infusions (weeks 16, 20 and 24). The ratio of these geometric means was the primary outcome measure.	During IVIG period (IV 1, IV 2, IV 3) and during SCIG period at weeks 16, 20, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Infection Episodes (Serious and Non-serious) by Study Period	Number of infection episodes (serious and non-serious) presented by study period: IVIG treatment: Study subjects were treated with their IVIG therapy with 3- or 4-weekly schedules for 3 dosing cycles (9 to 12 weeks; before being switched to SCIG treatment with IgPro20).; SCIG treatment (wash-in/wash-out; weeks 1 to 12): IgPro20 was administered subcutaneously with the first subcutaneous (SC) IgPro20 infusion starting 1 week after the last IVIG dose. Subjects were treated with weekly SC IgPro20 infusions for a 12-week wash-in/wash-out period. The IgPro20 dose was to be equal to the weekly equivalent dose of the previous IVIG therapy.; SCIG treatment (efficacy; weeks 13 to 24): After the SCIG wash-in/wash-out treatment, subjects were treated with weekly SC IgPro20 infusions for a 12-week efficacy period. The IgPro20 dose was to be equal to the weekly equivalent dose of the previous IVIG therapy.	Up to 36 weeks
Rate of Infection Episodes (Serious and Non-serious) by Study Period, PPS Population	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 specified study periods (listed below) and analysis population and adjusted to 365 days. Study periods: IVIG treatment (up to 12 weeks); SCIG IgPro20 treatment (wash-in/wash-out period) (12 weeks); SCIG IgPro20 treatment (efficacy) (12 weeks)	Up to 36 weeks
Rate of Infection Episodes (Serious and Non-serious) by Study Period, FAS Population	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 specified study periods (listed below) and analysis population and adjusted to 365 days. Study periods: IVIG treatment (up to 12 weeks); SCIG IgPro20 treatment (wash-in/wash-out period) (12 weeks); SCIG IgPro20 treatment (efficacy) (12 weeks)	Up to 36 weeks
Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections by Study Period	Median number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections, presented by study period: IVIG treatment (up to 12 weeks), SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks), and SCIG IgPro20 treatment (efficacy; 12 weeks).	Up to 36 weeks
Number of Days of Hospitalization Due to Infections by Study Period	Median number of days of hospitalization due to infections, presented by study period: IVIG treatment (up to 12 weeks), SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks), and SCIG IgPro20 treatment (efficacy; 12 weeks).	Up to 36 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, presented by study period: IVIG treatment (up to 12 weeks), SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks), and SCIG IgPro20 treatment (efficacy; 12 weeks).	Up to 36 weeks
Rate of All Adverse Events by Relatedness and Seriousness	The rate of adverse events (AEs) was the number of treatment-emergent AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.	For the duration of the study, up to 36 weeks
Rate of Mild, Moderate, or Severe Local Reactions	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 discomfort, infusion site erythema, infusion site haemorrhage, infusion site induration, infusion site inflammation, infusion site pain, infusion site pruritus, infusion site swelling, injection site erythema, injection site extravasation, injection site induration, injection site irritation, injection site pain, injection site pruritus, injection site swelling, and puncture site reaction. Mild AE: Symptoms are easily tolerated and there is no interference with daily activities; Moderate AE: Discomfort enough to cause some interference with daily activities; Severe AE: Incapacitating with inability to work or do usual activity.	For the duration of the study, up to 36 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Rate of Serious Bacterial Infections (SBIs), PPS Population	The annualized rate was based on the total number of SBIs and the total number of subject study days for all subjects in the specified study periods (listed below) and analysis population and adjusted to 365 days. Study periods: IVIG treatment (up to 12 weeks); SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks); SCIG IgPro20 treatment (efficacy; 12 weeks)	Up to 36 weeks
Annualized Rate of Serious Bacterial Infections (SBIs), FAS Population	The annualized rate was based on the total number of SBIs and the total number of subject study days for all subjects in the specified study periods (listed below) and analysis population and adjusted to 365 days. Study periods: IVIG treatment (up to 12 weeks); SCIG IgPro20 treatment (wash-in/wash-out; 12 weeks); SCIG IgPro20 treatment (efficacy; 12 weeks)	Up to 36 weeks

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Yoriyuki Shiga, CSL Behring K.K.

Publications and helpful links

General Publications

• Igarashi A, Kanegane H, Kobayashi M, Miyawaki T, Tsutani K. Cost-minimization analysis of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency. Clin Ther. 2014 Nov 1;36(11):1616-24. doi: 10.1016/j.clinthera.2014.08.007. Epub 2014 Sep 16.
• Kanegane H, Imai K, Yamada M, Takada H, Ariga T, Bexon M, Rojavin M, Hu W, Kobayashi M, Lawo JP, Nonoyama S, Hara T, Miyawaki T. Efficacy and safety of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency diseases. J Clin Immunol. 2014 Feb;34(2):204-11. doi: 10.1007/s10875-013-9985-z. Epub 2014 Feb 7.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: September 8, 2010
• First Submitted That Met QC Criteria: September 9, 2010
• First Posted (Estimate): September 13, 2010

Study Record Updates

• Last Update Posted (Estimate): December 12, 2014
• Last Update Submitted That Met QC Criteria: November 25, 2014
• Last Verified: March 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: ZLB06_002CR; U1111-1116-6379 (Other Identifier: WHO Universal Trial Number)