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

Sponsor

Baxalta now part of Shire (Industry)

Overall Status

Completed

CT.gov ID

NCT00782106

Collaborator

(none)

Enrollment

Locations

Arms

10.9

Actual Duration (Months)

3.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Primary Immunodeficiency Diseases (PID)	Biological: Recombinant human hyaluronidase + immune globulin intravenous Biological: Recombinant human hyaluronidase + immune globulin intravenous	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Intervention Model:

Parallel Assignment

Masking:

None (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)

Actual Study Start Date :

Dec 4, 2006

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
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: IGIV 10% = Immune Globulin Intraveneous (Human) 10% rHuPH20 = Recombinant Human Hyaluronidase
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: IGIV 10% = Immune Globulin Intraveneous (Human) 10% rHuPH20 = Recombinant Human Hyaluronidase

Arm

Intervention/Treatment

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:

IGIV

10% = Immune Globulin Intraveneous (Human)

10%

rHuPH20 = Recombinant Human Hyaluronidase

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:

IGIV

10% = Immune Globulin Intraveneous (Human)

10%

rHuPH20 = Recombinant Human Hyaluronidase

Outcome Measures

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. [72 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	First Allergy and Clinical Research Center	Centennial	Colorado	United States	80112
2	Allergy Associates of the Palm Beaches	North Palm Beach	Florida	United States	33408
3	Pediatrics Allergy/Immunology Association, PA	Dallas	Texas	United States	75230