Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy

Common Variable Immunodeficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00542997
• Other study ID #: 1460
• Secondary ID: ZLB06_001CR
• Status: Completed
• Phase: Phase 3
• First received: October 11, 2007
• Last updated: August 2, 2011
• Start date: September 2007
• Est. completion date: August 2009

Study information

• Verified date: August 2011
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Agammaglobulinemia
• Autosomal Recessive Agammaglobulinemia
• Common Variable Immunodeficiency
• Genetic Diseases, X-Linked
• Immunologic Deficiency Syndromes
• X-linked Agammaglobulinemia

Intervention

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.

Locations

Country	Name	City	State
France	Study site	Paris
Germany	Study site	Berlin
Germany	Study site	Düsseldorf
Germany	Study site	Freiburg
Germany	Study site	Hannover
Germany	Study site	Leipzig
Germany	Study site	Mainz
Germany	Study site	Munich
Italy	Study site	Brescia
Poland	Study site	Warsaw
Romania	Study site	Bucharest
Romania	Study site	Cluj-Napoca
Romania	Study site	Timisoara
Spain	Study site	Barcelona
Spain	Study site	Sevilla
Sweden	Study site	Göteborg
Switzerland	Study site	Berne
United Kingdom	Study site	Cardiff
United Kingdom	Study site	London

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

France,  Germany,  Italy,  Poland,  Romania,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (2)

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 imm — View Citation

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 intraveno — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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