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

• ClinicalTrials.gov Identifier: NCT00389324
• Recruitment Status: Completed
• First Posted: October 18, 2006
• Results First Posted: December 18, 2012
• Last Update Posted: April 20, 2015
• Sponsor: Grifols Therapeutics LLC
• Information provided by (Responsible Party): Grifols Therapeutics LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Immunologic Deficiency Syndrome	Biological: Immune Globulin Intravenous (Human)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2006
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: August 2008

Arms and Interventions

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; Immune globulin intravenous (Human)(IGIV); BAY 41-1000; TAL-05-00004; IGIV-C; IVIG; IGIVnex; NDC-13353-645-71; NDC-13353-646-24; NDC-13353-645-12; NDC-13353-645-15; NDC-13353-645-2

Outcome Measures

Primary Outcome Measures :

1. Geometric Least Square Means of Area Under the Curve (AUC) for Plasma Total Immunoglobulin G (IgG) [ Time Frame: 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 ]
   Geometric least-squares mean of steady-state plasma concentration of total IgG vs. time profile (AUC).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

University of California, Irvine

Irvine, California, United States, 92697

UCLA School of Medicine

Los Angeles, California, United States, 90095

United States, Georgia

Family Allergy & Asthma Center, PC

Atlanta, Georgia, United States, 30342

United States, Nebraska

Allergy, Asthma & Immunology Associates, PC

Omaha, Nebraska, United States, 68124

United States, Texas

Pediatric Allergy / Immunology Associates, PA

Dallas, Texas, United States, 75230

United States, Virginia

Virginia Commonwealth University

Richmond, Virginia, United States, 23219

Canada, British Columbia

Dr. Donald F. Stark, Inc

Vancouver, British Columbia, Canada, V6H3K2

Canada, Quebec

McGill University - Montreal General Hospital

Montreal, Quebec, Canada, H3G1A4

Sponsors and Collaborators

Grifols Therapeutics LLC

Investigators

• Study Director: Susan Sorrells; Grifols Therapeutics LLC

More Information

• Responsible Party: Grifols Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT00389324
• Other Study ID Numbers: 060001
• First Posted: October 18, 2006
• Results First Posted: December 18, 2012
• Last Update Posted: April 20, 2015
• Last Verified: March 2015

Keywords provided by Grifols Therapeutics LLC:

Primary immune deficiency

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes; Immune System Diseases; Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin; Immunoglobulin G; Immunologic Factors; Physiological Effects of Drugs