A Trial of the Pharmacokinetics, Safety, and Tolerability of Subcutaneous Gamunex® in Primary Immunodeficiency

An Open-Label Single-Sequence, Crossover Trial to Evaluate the Pharmacokinetics and Safety of Subcutaneous Gamunex® 10% (Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified) in Subjects With Primary Immunodeficiency

This study will compare the blood level of Gamunex in patients. Patients will take it as an injection under the skin or in a vein. The study will compare how safe and tolerable the two methods are in the patients. The patients in this study have a defect in their immune system from a genetic cause.

Study Overview

• Status: Completed
• Conditions: Immunologic Deficiency Syndrome
• Intervention / Treatment: Biological: Immune Globulin Intravenous (Human)

Detailed Description

This is an open-label, single-sequence, multi-center trial with subjects previously diagnosed with primary immune deficiency. Subjects will be on IGIV until a steady state is reached at which time PK profiling during the IV phase will occur. Subjects will begin SC administration 1 week following last IV dose and followed for a period of six months. PK profiling in SC phase will occur when subject reaches approximate steady-state on SC administration.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H3K2
      • Dr. Donald F. Stark, Inc
  • Quebec
    • Montreal, Quebec, Canada, H3G1A4
      • McGill University - Montreal General Hospital
• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Los Angeles, California, United States, 90095
      • UCLA School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Family Allergy & Asthma Center, PC
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Allergy, Asthma & Immunology Associates, PC
  • Texas
    • Dallas, Texas, United States, 75230
      • Pediatric Allergy / Immunology Associates, PA
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults and adolescents (age 13-75 inclusive) with a documented and confirmed pre-existing diagnosis of chronic primary immunodeficiency
• Previously or currently on IgG replacement therapy
• Documented (within 3 months) plasma IgG level of ≥500 mg/dL on current IgG therapy (IgG level can be obtained at the screening visit if documentation is not available)
• The medical records for all subjects within the previous 2 years should be available to document previous infections and treatment

Exclusion Criteria:

• Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the trial
• The subject has a known adverse reaction to Gamunex or other blood products
• The subject has a history of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections or other disorders where subcutaneous therapy would be contraindicated
• The subject has known selective IgA deficiency with the exception of a known selective IgA deficient subject who has no previous documented eventful reaction to products containing IgA
• The subject is pregnant or lactating
• The subject has significant proteinuria and/or has a history of acute renal failure and/or severe renal impairment (BUN or creatinine more than 2.5 times the upper limit of normal) and/or on dialysis
• The subject has known substance or prescription drug abuse in the past 12 months
• The subject has a history of or current diagnosis of deep venous thrombosis
• The subject has an acquired medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000 x 10e6/L), or HIV infection/AIDS
• The subject is receiving any of the following medications: corticosteroids (long-term daily, >1 mg of prednisone equivalent/kg/day for >30 days) (intermittent courses would not exclude subject); immunosuppressants; or immunomodulators
• The subject has non-controlled arterial hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg)
• The subject has anemia (hemoglobin <10 g/dL) at screening
• The subject has participated in another clinical trial within 30 days prior to screening (imaging studies without investigative treatments are permitted) or has received any investigational blood product within the previous 3 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Immune Globulin Intravenous (Human); Immune Globulin Intravenous (Human), 10%, Caprylate/Chromatography Purified

Biological: Immune Globulin Intravenous (Human); This trial was an open-label, single-sequence, study. The enrolled subjects received IGIV-C via two routes of administration (IV for 4 -5 weeks and SC for 24 weeks) in order to compare the PK variables, safety and tolerability of SC administration of IGIV-C. Certain subjects required IV IGIV-C dosing during a Run-in Phase (3 - 4 months) for steady-state conditions prior to the IV phase. Subjects received two IV infusions of IGIV (between 200 - 600 mg based on the subject's previous IgG dosing regimen, 3 to 4 weeks apart) until a steady-state was reached at which time PK profiling was performed. Subjects began weekly SC administration (1.37 times the weekly equivalency of each subject's monthly IV dose) 1 week following last IV dose and followed for a period of six months.; Other Names: Gamunex; Gaminex; IGIV-C; BAY 41-1000; TAL-05-00004; IVIG; IGIVnex; Immune globulin intravenous (Human)(IGIV); NDC-13353-645-71; NDC-13353-646-24; NDC-13353-645-12; NDC-13353-645-15; NDC-13353-645-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Least Square Means of Area Under the Curve (AUC) for Plasma Total Immunoglobulin G (IgG)	Geometric least-squares mean of steady-state plasma concentration of total IgG vs. time profile (AUC).	IV Phase (21 or 28 days) at IV Visit #1, pre- and post-dose: 0 hr., 1 hr., and 1, 2, 3, 5, 7, 14, 21, and 28 days; SC Phase at Week #17, pre- and post-dose: 0 hr., and 1, 3, 4, 5, and 7 days

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC
• Investigators: Study Director: Susan Sorrells, Grifols Therapeutics LLC

Publications and helpful links

Helpful Links

• FDA approved labeling information

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: October 17, 2006
• First Submitted That Met QC Criteria: October 17, 2006
• First Posted (Estimate): October 18, 2006

Study Record Updates

• Last Update Posted (Estimate): April 20, 2015
• Last Update Submitted That Met QC Criteria: March 31, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Primary immune deficiency
• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Immunoglobulin G
• Other Study ID Numbers: 060001 (Other Identifier: CINJ)