Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy

Overview

The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).

Full Title of Study: “A Multicentre Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 2009

Detailed Description

This study consisted of a 12-week wash-in/wash-out period followed by a 28-week efficacy period. During the 28-week efficacy period, subjects visited the study site at least every 4 weeks for efficacy and safety evaluations and additionally recorded details regarding IgPro20 dose and certain aspects of efficacy and safety in a diary. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects during 1 treatment interval at steady-state (Week 28 ± 1).

Interventions

  • Biological: Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)
    • 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.

Arms, Groups and Cohorts

  • Experimental: IgPro20

Clinical Trial Outcome Measures

Primary Measures

  • Total Serum IgG Trough Levels
    • Time Frame: Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)
    • Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject’s median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion.

Secondary Measures

  • Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population)
    • Time Frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
    • Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters. The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
  • Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population)
    • Time Frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
    • Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters. The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the PPE population and adjusted to 365 days.
  • Annual Rate of Infection Episodes
    • Time Frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
    • The annual rate of episodes was calculated based on the total number of any infection type and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
  • Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
    • Time Frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
    • The annual rate was calculated based on the total number of days out of work/school/kindergarten/day care or unable to perform normal activities due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
  • Annual Rate of the Number of Days of Hospitalization Due to Infections
    • Time Frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
    • The annual rate was calculated based on the total number of days of hospitalization due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
  • Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment
    • Time Frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
    • The annual rate was calculated based on the total number of days of antibiotic use in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.

Participating in This Clinical Trial

Inclusion Criteria

  • Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or Autosomal Recessive Agammaglobulinemia – Chest X-ray or CT scan obtained within 1 year prior to enrolment Exclusion Criteria:

  • Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy – 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 – Allergic or other severe reactions to immunoglobulins or other blood products associated with high anti-IgA Additional criteria may apply and examination by an investigator is required to determine eligibility.

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • CSL Behring
  • Provider of Information About this Clinical Study
    • Global Head Clinical R&D, CSL Behring
  • Overall Official(s)
    • Stephen Jolles, MD, Principal Investigator, University Hospital of Wales, Cardiff, UK

Citations Reporting on Results

Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, Belohradsky BH, Wahn V, Neufang-Hüber J, Zenker O, Grimbacher B. Efficacy and safety of Hizentra(®) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol. 2011 Oct;141(1):90-102. doi: 10.1016/j.clim.2011.06.002. Epub 2011 Jun 12.

Borte M, Pac M, Serban M, Gonzalez-Quevedo T, Grimbacher B, Jolles S, Zenker O, Neufang-Hueber J, Belohradsky B. Efficacy and safety of hizentra®, a new 20% immunoglobulin preparation for subcutaneous administration, in pediatric patients with primary immunodeficiency. J Clin Immunol. 2011 Oct;31(5):752-61. doi: 10.1007/s10875-011-9557-z. Epub 2011 Jun 15.

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