Study to Determine the Dose of Recombinant Human Hyaluronidase Needed to Infuse a Full Dose of IGIV Subcutaneously - Full Text View

Purpose

The purpose of the study is to determine the feasibility of infusing a full 4-week dose of Immune Globulin Intravenous (Human), 10% in a single subcutaneous site and the amount of recombinant human hyaluronidase needed to infuse that dose with no more than mild local adverse drug reactions.

Condition	Intervention	Phase
Primary Immune Deficiency	Biological: Recombinant human hyaluronidase + immune globulin intravenous	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 1/2 Determination of the Dose of Recominant Human Hyaluronidase (rHuPH20) Required Enabling Up to 600 mg/kg Bodyweight of IGIV, 10% to be Administered Subcutaneously in a Single Infusion Site in Subjects With Primary Immunodeficiency (PID)

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

Drug Information available for: Hyaluronidase Hyaluronidase (Human recombinant)

U.S. FDA Resources

Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:

Ability to administer, after priming with recombinant human hyaluronidase, at least one half of a 4-week dose (minimum of 200 mg/kg) of IgG in a single infusion site, via the subcutaneous route, with no more than mild local adverse drug reactions. [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]

Enrollment:	11
Study Start Date:	December 2006
Study Completion Date:	November 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Tolerability of subcutaneous infusions	Biological: Recombinant human hyaluronidase + immune globulin intravenous Dose (calculated) of rHuPH20 followed by subcutaneous infusion of IGIV, 10% to determine tolerability: doses of rHuPH20 and IGIV, 10% to be increased, as tolerated and as per protocol, until a full 4-week IgG dose can be administered Other Names: rHuPH20 = Recombinant Human Hyaluronidase IGIV, 10% = Immune Globulin Intraveneous (Human), 10%
Experimental: 2 Tolerability of subcutaneous infusions and pharmacokinetics	Biological: Recombinant human hyaluronidase + immune globulin intravenous IV infusion of IGIV, 10% to determine pharmacokinetics Intervention as in Arm 1: Dose (calculated) of rHuPH20 followed by subcutaneous infusion of IGIV, 10% to determine tolerability: doses of rHuPH20 and IGIV, 10% to be increased, as tolerated and as per protocol, until a full 4-week IgG dose can be administered Other Names: rHuPH20 = Recombinant Human Hyaluronidase IGIV, 10% = Immune Globulin Intraveneous (Human), 10%

Arms

Assigned Interventions

Experimental: 1

Tolerability of subcutaneous infusions

Biological: Recombinant human hyaluronidase + immune globulin intravenous

Dose (calculated) of rHuPH20 followed by subcutaneous infusion of IGIV, 10% to determine tolerability: doses of rHuPH20 and IGIV, 10% to be increased, as tolerated and as per protocol, until a full 4-week IgG dose can be administered

Other Names:

rHuPH20 = Recombinant Human Hyaluronidase
IGIV, 10% = Immune Globulin Intraveneous (Human), 10%

Experimental: 2

Tolerability of subcutaneous infusions and pharmacokinetics

Biological: Recombinant human hyaluronidase + immune globulin intravenous

IV infusion of IGIV, 10% to determine pharmacokinetics
Intervention as in Arm 1: Dose (calculated) of rHuPH20 followed by subcutaneous infusion of IGIV, 10% to determine tolerability: doses of rHuPH20 and IGIV, 10% to be increased, as tolerated and as per protocol, until a full 4-week IgG dose can be administered

Other Names:

rHuPH20 = Recombinant Human Hyaluronidase
IGIV, 10% = Immune Globulin Intraveneous (Human), 10%

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Written informed consent from either the subject or the subject's legally acceptable representative
Diagnosis of a PID disorder as defined by World Health Organization criteria1 for which the subject had been receiving a regimen of weekly or biweekly (every-other-week) subcutaneous IgG infusions or IGIV infusions every 21 to 28 days over a period of at least 8 weeks pre-study at an equivalent of a 4-week dose of 300 to 800 mg/kg bodyweight
Adults/adolescents aged 16 years and older)
For female subjects of child-bearing age: negative urine pregnancy test result at study entry and agreement to employ adequate birth control measures for the duration of the study

Exclusion Criteria:

Subjects positive at enrollment for one or more of the following: HBsAg, PCR for HCV, PCR for HIV Type 1
Subjects with levels of alanine aminotransferase (ALT) or aspartate aminotransferase (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 current history of malignancy
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 in the opinion of the investigator precluded phlebotomy for laboratory studies
Subjects who had been exposed to any blood or blood product other than an intravenous immunoglobulin (IGIV), SC immunoglobulin (SCIG), immune serum globulin (ISG) preparations, or albumin within the 6 months prior to study entry.
Subjects with an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SCIG and/or ISG infusions
Subjects with IgA deficiency and known anti IgA antibodies
Subjects who had received antibiotic therapy for the treatment of infection within 7 days prior to enrollment
Subjects who had participated in another clinical study involving an investigational product or device within 28 days prior to study entry
Subjects with inability or unwillingness to meet all the requirements of this study
If female, pregnancy or lactation at time of study entry

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00782106

Locations

United States, Colorado
First Allergy and Clinical Research Center
Centennial, Colorado, United States, 80112
United States, Florida
Allergy Associates of the Palm Beaches
North Palm Beach, Florida, United States, 33408
United States, Texas
Pediatrics Allergy/Immunology Association, PA
Dallas, Texas, United States, 75230

Sponsors and Collaborators

Baxter Healthcare Corporation

More Information

No publications provided

Responsible Party:	Richard Schiff, MD, PhD; Medical Director, Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:	NCT00782106 History of Changes
Other Study ID Numbers:	160602
Study First Received:	October 29, 2008
Last Updated:	October 28, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013