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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01199705
First received: September 8, 2010
Last updated: May 26, 2014
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Primary Immune Deficiency
Biological: Immune Globulin Subcutaneous (Human) (SCIG)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Study of Efficacy, Safety, Tolerability, and Pharmacokinetics of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency

Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • IgG Trough Level [ Time Frame: During IVIG period (IV 1, IV 2, IV 3) and during SCIG period at weeks 16, 20, and 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Infection Episodes (Serious and Non-serious) by Study Period [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    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.

  • Rate of Infection Episodes (Serious and Non-serious) by Study Period, PPS Population [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    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)

  • Rate of Infection Episodes (Serious and Non-serious) by Study Period, FAS Population [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    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)

  • Number of Days Out of Work/School/Kindergarten/Day Care or Unable to Perform Normal Daily Activities Due to Infections by Study Period [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]
    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).

  • Number of Days of Hospitalization Due to Infections by Study Period [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]
    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).

  • Duration of Use of Antibiotics for Infection Prophylaxis and Treatment [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]
    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).

  • Rate of All Adverse Events by Relatedness and Seriousness [ Time Frame: For the duration of the study, up to 36 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Rate of Mild, Moderate, or Severe Local Reactions [ Time Frame: For the duration of the study, up to 36 weeks ] [ Designated as safety issue: Yes ]

    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.



Other Outcome Measures:
  • Annualized Rate of Serious Bacterial Infections (SBIs), PPS Population [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    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)

  • Annualized Rate of Serious Bacterial Infections (SBIs), FAS Population [ Time Frame: Up to 36 weeks ] [ Designated as safety issue: No ]

    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)


Enrollment: 25
Study Start Date: September 2010
Study Completion Date: November 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Hizentra

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01199705

Locations
Japan
Study site
Nagoya city, Aichi Pref., Japan, 466-8560
Study site
Chiba city, Chiba Pref., Japan, 260-8677
Study site
Gifu city, Gifu Pref., Japan, 501-1194
Study site
Sapporo city, Hokkaido, Japan, 060-8648
Study site
Sendai city, Miyagi Pref., Japan, 980-8574
Study site
Fukuoka city, Osaka, Japan, 812-8582
Study site
Moriguchi city, Osaka, Japan, 570-8507
Study site
Osaka city, Osaka, Japan, 534-0021
Study site
Koshigaya city, Saitama Pref., Japan, 343-8555
Study site
Tokorozawa city, Saitama Pref., Japan, 359-8513
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Yoriyuki Shiga CSL Behring K.K.
  More Information

Additional Information:
Publications:
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01199705     History of Changes
Other Study ID Numbers: ZLB06_002CR, U1111-1116-6379
Study First Received: September 8, 2010
Results First Received: January 1, 2013
Last Updated: May 26, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by CSL Behring:
Immune globulin subcutaneous
SCIG
Primary immunodeficiency
PID

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014