Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy

Phase 3CompletedNCT00419341

CSL Behring49 enrolled

Overview

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

The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Immune Deficiency

Interventions

Human Normal Immunoglobulin for Subcutaneous AdministrationBIOLOGICAL

Eligibility

Sex: ALLMin age: 2 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female aged 2 to 75 years * Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia) * Written informed consent Exclusion Criteria: * Newly diagnosed PID * Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis) * Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma * Known hyperprolinemia * Hypoalbuminemia, protein-losing enteropathies, and any proteinuria * Allergic reactions to immunoglobulins or other blood products * Known antibodies to Immunoglobulin A (IgA) * The subject is receiving steroids (oral and parenteral, daily ≥ 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants * Female who is pregnant, breast feeding or planning a pregnancy during the course of the study * Participation in a study with an investigational product other than (IVIG) within 1 month prior to enrollment * A positive result at screening on any of the following viral markers: Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV) * Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration \> 2.5 times the upper normal limit (UNL) * Creatinine concentration \> 1.5 times the UNL * Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial

Locations (13)

Study Site

Los Angeles, California, United States

Study Site

Los Angeles, California, United States

Study Site

Centennial, Colorado, United States

Outcomes

Primary Outcomes

Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)

The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)

Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03\_002CR \[NCT00168025\] or ZLB05\_006CR \[NCT00322556\]).

Time frame: Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment

Secondary Outcomes

Annualized Rate of Clinically Documented SBIs (ITT Population)

The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.

Time frame: For the duration of the study, up to 15 months

Annualized Rate of Clinically Documented SBIs (PPE Population)

Data from ClinicalTrials.gov

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Study Site

North Palm Beach, Florida, United States

Study Site

Atlanta, Georgia, United States

Study Site

Fort Wayne, Indiana, United States

Study Site

Indianapolis, Indiana, United States

Study Site

Iowa City, Iowa, United States

Study Site

St Louis, Missouri, United States

Study Site

Newark, New Jersey, United States

...and 3 more locations

The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Annualized Rate of Infection Episodes

The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Time frame: Efficacy period: up to 12 months (week 13 to completion visit)

Number of Infection Episodes (Serious and Non-serious)

Total number of infections for the specified analysis population

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections

The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections

Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Annualized Rate of Hospitalization Due to Infection

The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Number of Days of Hospitalization Due to Infections

Total number of days of hospitalization due to infections for the specified analysis population

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Use of Antibiotics for Infection Prophylaxis and Treatment

Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.

Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)

Total Serum IgG Trough Levels

The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.

Time frame: Every 4 weeks, throughout the 12-month efficacy period

Maximum Concentration (Cmax) of Total Serum IgG at Steady State

Time frame: Week 28 ± 1 week of the treatment period

Tmax at Steady State

Timepoint of maximum concentration (Cmax)

Time frame: Week 28 ± 1 week of the treatment period