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

Condition(s) targeted: Immunologic Deficiency Syndrome

Intervention: Immune Globulin Intravenous (Human), 10%, Caprylate/Chromatography Purified (Gamunex) (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Talecris Biotherapeutics

Official(s) and/or principal investigator(s):
Jamie Schimmel, MPA, Study Director, Affiliation: Talecris Biotherapeutics

This study will investigate the pharmacokinetics (PK), safety and tolerability of GAMUNEX administered subcutaneously (SC) in subjects with Primary Immune Deficiency (PID). Gamunex is a ready to use 10% solution Immunoglobulin G (IgG) currently approved for intravenous (IV) administration for the treatment of PID. The goal is to demonstrate based on PK evaluation that Gamunex administered SC with an appropriate dose conversion factor will achieve a steady-state AUC of plasma IgG to be non-inferior to that achieved by the corresponding dose utilizing IV Gamunex therapy.

Official title: An Open-Label Single-Sequence, Crossover Trial to Evaluate the Pharmacokinetics, Safety, and Tolerability, of Subcutaneous Gamunex® 10% in Subjects With Primary Immunodeficiency

Study design: Treatment, Non-Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics Study

Primary outcome:

To demonstrate the safety and tolerability of SC administered Gamunex

AUC 0-7 days following the weekly SC infusion, i.e., the AUC over a weekly SC dosing interval under an approximate steady-state condition.

AUC 0-28 days following the monthly IV infusion, i.e., the AUC over a monthly IV dosing interval under an approximate steady-state condition.

Secondary outcome: Maximum level (Cmax) of IgG following SC or IV administration

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 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.

Minimum age: 13 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adults and adolescents (age 13-75 inclusive) with a documented and confirmed

pre-existing diagnosis of chronic primary immune deficiency

- 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 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 10e9/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

Dr. Donald F. Stark, Inc, Vancouver, British Columbia V6H3K2, Canada

UCLA School of Medicine, Los Angeles, California 90095, United States

Univesity of California, Irving, Irvine, California 92697, United States

Family Allergy & Asthma Center, PC, Atlanta, Georgia 30342, United States

Allergy, Asthma & Immunology Associates, PC, Omaha, Nebraska 68124, United States

McGill University - Montreal General Hospital, Montreal, Quebec H3G1A4, Canada

Pediatric Allergy / Immunology Associates, PA, Dallas, Texas 75230, United States

Virginia Commonwealth University, Richmond, Virginia 23219, United States

FDA approved labeling information

Starting date: November 2006
Ending date: August 2008
Last updated: January 22, 2008