Comparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects

Baxalta now part of Shire49 enrolled

Overview

The purpose of this study is to evaluate the tolerability of IGIV, 10% given subcutaneously and the pharmacokinetics of immunoglobulin G (IgG) following subcutaneous (SC) treatment with IGIV, 10% in subjects with primary immunodeficiency (PID) disorders.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Immunodeficiency Diseases (PID)

Interventions

Immune Globulin Intravenous (Human), 10%DRUG

Intravenous administration in Study Part 1, subcutaneous administration in Study Parts 2 and 3

Eligibility

Sex: ALLMin age: 24 Months

Medical Language ↔ Plain English

Inclusion Criteria: * Written informed consent obtained from either the subject or the subject's legally acceptable representative prior to any study-related procedures and study product administration * Diagnosis of a PID disorder as defined by World Health Organization criteria (IUIS Scientific Committee, Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol. 1999) for which the subject has been receiving a regular regimen of IV immunoglobulin infusions every 21 ± 3 days or 28 ± 3 days or a regular SC immunoglobulin treatment at 1 to 2 week intervals over a period of at least 3 months pre-study at a dose of 300-800 mg/kg BW/4 weeks * Subjects are aged 2 years or older * Subjects have a serum trough level of IgG \> 4.5 g/L at the last documented determination * A negative serum pregnancy test for any female subject who is of childbearing potential * Female subjects of childbearing potential agree to practice birth control measures for the duration of the study Exclusion Criteria: * Subjects positive at enrollment for one or more of the following: Hepatitis B surface antigen (HBsAg), PCR for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1 * Subjects with levels of alanine amino transferase (ALT) or aspartate amino transferase (AST) \> 2.5 times the upper limit of normal for the testing laboratory * Subjects with neutropenia (defined as an absolute neutrophil count \[ANC\] \<= 500/mm3) * Subjects with serum creatinine levels greater than 1.5 times the upper limit of normal for age and gender * Subjects with a malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * Subjects with a history of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident) * Subjects with abnormal protein loss (protein losing enteropathy, nephritic syndrome, severe lung disease) * Subjects with anemia that would preclude phlebotomy for laboratory studies * Subjects who received any blood or blood product other than an IGIV, SC immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to study enrollment * Subjects with an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC immunoglobulin and/or ISG infusions * Subjects with IgA deficiency and known anti IgA antibodies * Subjects receiving antibiotic therapy for the treatment of infection within 7 days prior to enrollment * Subjects participating in another clinical study involving an investigational product or device within 28 days prior to study enrollment * Subjects with bleeding disorders or who are on anti-coagulation therapy

Locations (9)

Unnamed facility

Los Angeles, California, United States

Unnamed facility

Centennial, Colorado, United States

Unnamed facility

North Palm Beach, Florida, United States

Unnamed facility

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage

Expressed as (AUC\_SC/AUC\_IV) \* 100

Time frame: Week 12 (IV) and week 32 or 33 (SC)

Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.

Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)

Time frame: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation

Percentage of Participants in Full Safety Data Set (FSDS) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped

Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs

Time frame: Throughout study (1 year and 9 months)

Percentage of Participants Naïve to SC Administration of Immunoglobulins (SNSC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped.

Time frame: Throughout study (1 year and 9 months)

Percentage of Participants With Prior Experience With Subcutaneous Administration of Immunoglobulins (SESC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped

Data from ClinicalTrials.gov

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Secondary Outcomes

Study Part 1 (IV): Maximum Plasma Concentration (C-max)

Maximal immune globulin concentration after infusion

Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Study Part 1 (IV): Minimum Plasma Concentration (C-min)

Minimal immune globulin concentration after infusion

Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Study Part 1 (IV): Weight-adjusted Clearance

Computed as weight-adjusted dose divided by total AUC

Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Study Part 1 (IV): Terminal Half-life

Computed from the regression slope in the terminal phase of the model (the slope is biphasic). Terminal half life is the time it takes for the plasma concentration or the amount of immunoglobulin in the body to be reduced by 50%during the terminal phase.

Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max)

Maximal immune globulin concentration after infusion