Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy

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

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

Study Overview

• Status: Completed
• Conditions: Common Variable Immunodeficiency; X-linked Agammaglobulinemia; Autosomal Recessive Agammaglobulinemia
• Intervention / Treatment: Biological: Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)

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).

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75743
    • Study Site
• Germany
  • Berlin, Germany, 13353
    • Study Site
  • Düsseldorf, Germany, 40001
    • Study Site
  • Freiburg, Germany, 79095
    • Study Site
  • Hannover, Germany, 30625
    • Study Site
  • Leipzig, Germany, 04129
    • Study Site
  • Mainz, Germany, 55131
    • Study Site
  • Munich, Germany, 80337
    • Study Site
• Italy
  • Brescia, Italy, 25123
    • Study Site
• Poland
  • Warsaw, Poland, 04-736
    • Study Site
• Romania
  • Bucharest, Romania, 020393
    • Study Site
  • Cluj-Napoca, Romania, 400162
    • Study Site
  • Timisoara, Romania, 300011
    • Study Site
• Spain
  • Barcelona, Spain, 08036
    • Study Site
  • Sevilla, Spain, 41013
    • Study Site
• Sweden
  • Göteborg, Sweden, 41685
    • Study Site
• Switzerland
  • Berne, Switzerland, 3010
    • Study Site
• United Kingdom
  • Cardiff, United Kingdom, CF 14 4XW
    • Study Site
  • London, United Kingdom, NW3 2QG
    • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IgPro20

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.; Other Names: Hizentra; SCIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Serum IgG Trough Levels	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.	Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population)	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.	Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population)	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.	Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Infection Episodes	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.	Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections	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.	Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of the Number of Days of Hospitalization Due to Infections	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.	Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment	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.	Efficacy period: week 12 to week 40 after study start or to the completion visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of Total Serum IgG		Week 28 (±1week)
Timepoint of Maximum Concentration (Tmax) of Total Serum IgG		Week 28 (±1week)
Area Under the Concentration-Time Curve (AUC_last) of Total Serum IgG	AUC_last = Area under the concentration-time curve until last measured concentration.	Week 28 (±1week)
Area Under the Concentration-Time Curve (AUCτ) of Total Serum IgG	AUCτ = Area under the concentration-time curve during regular dosing interval;	Week 28 (±1week)

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Principal Investigator: Stephen Jolles, MD, University Hospital of Wales, Cardiff, UK

Publications and helpful links

General Publications

• Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, Belohradsky BH, Wahn V, Neufang-Huber J, Zenker O, Grimbacher B. Efficacy and safety of Hizentra((R)) 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(R), 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: October 11, 2007
• First Submitted That Met QC Criteria: October 11, 2007
• First Posted (Estimate): October 12, 2007

Study Record Updates

• Last Update Posted (Estimate): September 1, 2011
• Last Update Submitted That Met QC Criteria: August 2, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: SCIG; Subcutaneous immune globulin
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hematologic Diseases; Blood Protein Disorders; Immunologic Deficiency Syndromes; Agammaglobulinemia; Common Variable Immunodeficiency; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: 1460; ZLB06_001CR (Other Identifier: CSL Behring)