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Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy

This study has been completed.
Sponsor:
Information provided by:
CSL Behring
ClinicalTrials.gov Identifier:
NCT00542997
First received: October 11, 2007
Last updated: August 2, 2011
Last verified: August 2011
  Purpose

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


Condition Intervention Phase
Common Variable Immunodeficiency
X-linked Agammaglobulinemia
Autosomal Recessive Agammaglobulinemia
Biological: Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)
Phase 3

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

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome 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) ] [ Designated as safety issue: No ]
    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 Outcome 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 51
Study Start Date: September 2007
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   2 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT00542997

Locations
France
Study site
Paris, France, 75743
Germany
Study site
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
Italy
Study site
Brescia, Italy, 25123
Poland
Study site
Warsaw, Poland, 04-736
Romania
Study site
Bucharest, Romania, 020393
Study site
Cluj-Napoca, Romania, 400162
Study site
Timisoara, Romania, 300011
Spain
Study site
Barcelona, Spain, 08036
Study site
Sevilla, Spain, 41013
Sweden
Study site
Göteborg, Sweden, 41685
Switzerland
Study site
Berne, Switzerland, 3010
United Kingdom
Study site
Cardiff, United Kingdom, CF 14 4XW
Study site
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
CSL Behring
Investigators
Principal Investigator: Stephen Jolles, MD University Hospital of Wales, Cardiff, UK
  More Information

Additional Information:
Publications:
Responsible Party: Global Head Clinical R&D, CSL Behring
ClinicalTrials.gov Identifier: NCT00542997     History of Changes
Other Study ID Numbers: 1460, ZLB06_001CR
Study First Received: October 11, 2007
Results First Received: February 8, 2011
Last Updated: August 2, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by CSL Behring:
Subcutaneous immune globulin
SCIG

Additional relevant MeSH terms:
Agammaglobulinemia
Common Variable Immunodeficiency
Genetic Diseases, X-Linked
Immunologic Deficiency Syndromes
Blood Protein Disorders
Genetic Diseases, Inborn
Hematologic Diseases
Immune System Diseases
Lymphatic Diseases
Lymphoproliferative Disorders
Antibodies
Immunoglobulins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014