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

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)

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.

Study Overview

• Status: Completed
• Conditions: Primary Immunodeficiency Diseases (PID)
• Intervention / Treatment: Biological: Recombinant human hyaluronidase + immune globulin intravenous; Biological: Recombinant human hyaluronidase + immune globulin intravenous

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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; 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
Experimental: 2; Tolerability of subcutaneous infusions and pharmacokinetics	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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: October 29, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• 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: 160602