search
Back to results

Tolerability and Safety of IGI, 10% With rHuPH20 in PIDD

Primary Purpose

Primary Immunodeficiency Diseases (PID)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Immune Globulin Infusion (Human), 10%
Recombinant human hyaluronidase
Sponsored by
Baxalta now part of Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immunodeficiency Diseases (PID) focused on measuring PIDD

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the IUIS Scientific Committee 2009 and by diagnostic criteria according to Conley et al. The diagnosis must be reviewed by the Medical Director prior to enrollment.
  • Subject is 2 years or older at the time of screening.
  • Written informed consent is obtained from either the subject or the subject's legally authorized representative prior to any study-related procedures and study product administration.
  • Subject has been receiving a consistent dose of immunoglobulin G (IgG) with a non-Baxter product (Gammunex administered IV, Hizentra, or Privigen), administered in compliance with the respective product information, for a period of at least 3 months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW/4 weeks and a maximum dose equivalent to 600 mg/kg BW/4 weeks at a dosing frequency as follows:

    • For IV treatment prior to the study: at mean intervals of 3 or 4 weeks (+/- 3 days) or
    • For SC treatment prior to the study: at mean intervals of approximately 1 or 2 weeks (+/- 2 days).
  • Subject has a serum trough level of IgG > 5 g/L at screening.
  • Subject has not had a serious bacterial infection within the 3 months prior to screening.
  • If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
  • Subject is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

  • Subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.
  • Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):

    • Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
    • Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3).
  • Subject has creatinine clearance (CLcr) value that is <60% of normal for age and gender either measured, or calculated according to a gender-specific formula provided in the study protocol.
  • Subject has been diagnosed with or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years
  • Subject is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia.
  • Subject has abnormal protein loss (protein losing enteropathy, nephrotic syndrome).
  • Subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
  • Subject has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
  • Subject has immunoglobulin A (IgA) deficiency (IgA less than 0.07g/L) and known anti IgA antibodies.
  • Subject has a known allergy to hyaluronidase.
  • Subject is on preventative (prophylactic) systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics at the time of screening.
  • Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
  • Subject has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy.
  • Subject has total protein > 9 g/dL or myeloma, or macroglobulinemia (IgM) or paraproteinemia.
  • Women of childbearing potential meeting any one of the following criteria:

    • Subject presents with a positive pregnancy test
    • Subject is breast feeding
    • Subject intends to begin nursing during the course of the study
    • Subject does not agree to employ adequate birth-control measures (e.g. intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study.
  • Subject has participated in another clinical study and has been exposed to an investigational product (IP) or device within 30 days prior to study enrollment (exception: treatment with immunoglobulin pre-study).
  • Subject is scheduled to participate in another (non-Baxter) clinical study involving an IP or device during the course of the study.
  • Subject has severe dermatitis that would preclude adequate sites for safe product administration.

Sites / Locations

  • University of California, Irvine
  • IMMUNOe International Research Centers
  • Allergy Associates of the Palm Beaches, PA
  • LSU Health Sciences Center & Children´s Hospital
  • Midwest Immunology
  • Midlands Pediatrics PC
  • Winthrop Allergy and Immunology
  • Oklahoma Institute of Allergy & Asthma Clinical Research
  • Allergy and Clinical Immunology Associates
  • Allergy, Asthma & Immunology Clinic PA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Epoch 1 and Epoch 2

Arm Description

In Study Epoch 1 PIDD patients that are already on intravenous treatment or subcutaneous treatment will be enrolled and treated with IGI, 10% and rHuPH20 subcutaneously, with a short dose/interval ramp-up (Epoch 1) consisting of one 1-week dose and interval and one 2-week dose and interval. The ramp-up (Epoch 1) is followed by Epoch 2 which consists of approximately 6 months (24 weeks) of IGI, 10% and rHuPH20 treatment. For subjects pretreated intravenously (IV), this treatment will occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), depending on the subject´s previous IV dosing schedule. For subjects pretreated subcutaneously (SC), treatment will also occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), at the discretion of the investigator and subject.

Outcomes

Primary Outcome Measures

Number of Related Systemic Adverse Events (Excluding Infections)
Rate of Related Systemic Adverse Events (Excluding Infections) Per Infusion
A point estimate and 95% confidence interval for the rate of related systemic adverse events per infusion was derived using a Poisson model.

Secondary Outcome Measures

Proportion of Subjects Who Achieve a Treatment Interval of 3 or 4 Weeks in Epoch 2
Proportion of Subjects Who Maintain a Treatment Interval of 3 or 4 Weeks in Epoch 2 for 24 Weeks
Number of Related Local Adverse Events (Excluding Infections)
Rate of Related Local Adverse Events (Excluding Infections) Per Infusion
A point estimate and 95% confidence interval for the rate of related local adverse events per infusion was derived using a Poisson model.
Number of All Related Adverse Events (Excluding Infections)
Rate of All Adverse Events (Excluding Infections) Per Infusion
A point estimate and 95% confidence interval for the rate of adverse events per infusion was derived using a Poisson model.
Number of Subjects Who Develop Neutralizing Antibodies to rHuPH20
Trough Levels of Immunoglobulin G (IgG)
IgG trough levels at the beginning of Study Epoch 1 (previous immunoglobulin treatment) and at the end of Study Epoch 2 were analyzed.
Number of Infusions Per Month in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Number of Infusion Sites (Needle Sticks) Per Month in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Duration of Infusion in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Maximum Infusion Rate in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Number of Weeks to Reach Final 3 or 4-week Dose Interval
Non-parametric descriptive statistics (median, range) are provided.

Full Information

First Posted
December 2, 2011
Last Updated
April 30, 2021
Sponsor
Baxalta now part of Shire
search

1. Study Identification

Unique Protocol Identification Number
NCT01485796
Brief Title
Tolerability and Safety of IGI, 10% With rHuPH20 in PIDD
Official Title
Tolerability, Safety and Administration Mode Evaluation of Recombinant Human Hyaluronidase (rHuPH20) Facilitated Subcutaneous Treatment With Immune Globulin Infusion (Human), 10% in Subjects With Primary Immunodeficiency Diseases (PIDD)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
December 29, 2011 (Actual)
Primary Completion Date
January 1, 2013 (Actual)
Study Completion Date
January 1, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to acquire additional data on safety and tolerability of recombinant human hyaluronidase (rHuPH20) facilitated subcutaneous treatment of Immune Globulin Infusion (Human), 10% (IGI, 10%) and to assess the mode of product administration. Following a discussion with the FDA at the end of July 2012, all participants still active in the study stopped treatment with rHuPH20 to assure safety of the participants participating in the study and went into a safety follow-up. During this safety follow-up period, participants underwent treatment with the licensed product IGI, 10% (Gammagard Liquid). The intravenous or subcutaneous administration route was at the discretion of the participant and the investigator.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency Diseases (PID)
Keywords
PIDD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Epoch 1 and Epoch 2
Arm Type
Experimental
Arm Description
In Study Epoch 1 PIDD patients that are already on intravenous treatment or subcutaneous treatment will be enrolled and treated with IGI, 10% and rHuPH20 subcutaneously, with a short dose/interval ramp-up (Epoch 1) consisting of one 1-week dose and interval and one 2-week dose and interval. The ramp-up (Epoch 1) is followed by Epoch 2 which consists of approximately 6 months (24 weeks) of IGI, 10% and rHuPH20 treatment. For subjects pretreated intravenously (IV), this treatment will occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), depending on the subject´s previous IV dosing schedule. For subjects pretreated subcutaneously (SC), treatment will also occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), at the discretion of the investigator and subject.
Intervention Type
Biological
Intervention Name(s)
Immune Globulin Infusion (Human), 10%
Other Intervention Name(s)
IGI, 10%
Intervention Description
Subcutaneous administration will be used in Study Epochs 1 and 2.
Intervention Type
Biological
Intervention Name(s)
Recombinant human hyaluronidase
Other Intervention Name(s)
rHuPH20
Intervention Description
rHuPH20 will be administered subcutaneously (SC) immediately before each SC IGI, 10% infusion, through the same needle, at a rate of 1 to 2 mL/min.
Primary Outcome Measure Information:
Title
Number of Related Systemic Adverse Events (Excluding Infections)
Time Frame
7 months (per subject)
Title
Rate of Related Systemic Adverse Events (Excluding Infections) Per Infusion
Description
A point estimate and 95% confidence interval for the rate of related systemic adverse events per infusion was derived using a Poisson model.
Time Frame
7 months (per subject)
Secondary Outcome Measure Information:
Title
Proportion of Subjects Who Achieve a Treatment Interval of 3 or 4 Weeks in Epoch 2
Time Frame
6 months (per subject)
Title
Proportion of Subjects Who Maintain a Treatment Interval of 3 or 4 Weeks in Epoch 2 for 24 Weeks
Time Frame
6 months (per subject)
Title
Number of Related Local Adverse Events (Excluding Infections)
Time Frame
7 months (per subject)
Title
Rate of Related Local Adverse Events (Excluding Infections) Per Infusion
Description
A point estimate and 95% confidence interval for the rate of related local adverse events per infusion was derived using a Poisson model.
Time Frame
7 months (per subject)
Title
Number of All Related Adverse Events (Excluding Infections)
Time Frame
7 months (per subject)
Title
Rate of All Adverse Events (Excluding Infections) Per Infusion
Description
A point estimate and 95% confidence interval for the rate of adverse events per infusion was derived using a Poisson model.
Time Frame
7 months (per subject)
Title
Number of Subjects Who Develop Neutralizing Antibodies to rHuPH20
Time Frame
7 months (per subject)
Title
Trough Levels of Immunoglobulin G (IgG)
Description
IgG trough levels at the beginning of Study Epoch 1 (previous immunoglobulin treatment) and at the end of Study Epoch 2 were analyzed.
Time Frame
7 months (per subject)
Title
Number of Infusions Per Month in Epoch 1 and Epoch 2
Description
Non-parametric descriptive statistics (median, range) are provided.
Time Frame
7 months (per subject)
Title
Number of Infusion Sites (Needle Sticks) Per Month in Epoch 1 and Epoch 2
Description
Non-parametric descriptive statistics (median, range) are provided.
Time Frame
7 months (per subject)
Title
Duration of Infusion in Epoch 1 and Epoch 2
Description
Non-parametric descriptive statistics (median, range) are provided.
Time Frame
7 months (per subject)
Title
Maximum Infusion Rate in Epoch 1 and Epoch 2
Description
Non-parametric descriptive statistics (median, range) are provided.
Time Frame
7 months (per subject)
Title
Number of Weeks to Reach Final 3 or 4-week Dose Interval
Description
Non-parametric descriptive statistics (median, range) are provided.
Time Frame
7 months (per subject)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the IUIS Scientific Committee 2009 and by diagnostic criteria according to Conley et al. The diagnosis must be reviewed by the Medical Director prior to enrollment. Subject is 2 years or older at the time of screening. Written informed consent is obtained from either the subject or the subject's legally authorized representative prior to any study-related procedures and study product administration. Subject has been receiving a consistent dose of immunoglobulin G (IgG) with a non-Baxter product (Gammunex administered IV, Hizentra, or Privigen), administered in compliance with the respective product information, for a period of at least 3 months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW/4 weeks and a maximum dose equivalent to 600 mg/kg BW/4 weeks at a dosing frequency as follows: For IV treatment prior to the study: at mean intervals of 3 or 4 weeks (+/- 3 days) or For SC treatment prior to the study: at mean intervals of approximately 1 or 2 weeks (+/- 2 days). Subject has a serum trough level of IgG > 5 g/L at screening. Subject has not had a serious bacterial infection within the 3 months prior to screening. If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study. Subject is willing and able to comply with the requirements of the protocol. Exclusion Criteria: Subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2. Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent): Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3). Subject has creatinine clearance (CLcr) value that is <60% of normal for age and gender either measured, or calculated according to a gender-specific formula provided in the study protocol. Subject has been diagnosed with or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years Subject is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia. Subject has abnormal protein loss (protein losing enteropathy, nephrotic syndrome). Subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site. Subject has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions. Subject has immunoglobulin A (IgA) deficiency (IgA less than 0.07g/L) and known anti IgA antibodies. Subject has a known allergy to hyaluronidase. Subject is on preventative (prophylactic) systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics at the time of screening. Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening. Subject has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy. Subject has total protein > 9 g/dL or myeloma, or macroglobulinemia (IgM) or paraproteinemia. Women of childbearing potential meeting any one of the following criteria: Subject presents with a positive pregnancy test Subject is breast feeding Subject intends to begin nursing during the course of the study Subject does not agree to employ adequate birth-control measures (e.g. intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study. Subject has participated in another clinical study and has been exposed to an investigational product (IP) or device within 30 days prior to study enrollment (exception: treatment with immunoglobulin pre-study). Subject is scheduled to participate in another (non-Baxter) clinical study involving an IP or device during the course of the study. Subject has severe dermatitis that would preclude adequate sites for safe product administration.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
IMMUNOe International Research Centers
City
Thornton
State/Province
Colorado
ZIP/Postal Code
80233
Country
United States
Facility Name
Allergy Associates of the Palm Beaches, PA
City
North Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
LSU Health Sciences Center & Children´s Hospital
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Midwest Immunology
City
Plymouth
State/Province
Minnesota
ZIP/Postal Code
55446
Country
United States
Facility Name
Midlands Pediatrics PC
City
Papillion
State/Province
Nebraska
ZIP/Postal Code
68046
Country
United States
Facility Name
Winthrop Allergy and Immunology
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Oklahoma Institute of Allergy & Asthma Clinical Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73131
Country
United States
Facility Name
Allergy and Clinical Immunology Associates
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15241
Country
United States
Facility Name
Allergy, Asthma & Immunology Clinic PA
City
Irving
State/Province
Texas
ZIP/Postal Code
75063
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Tolerability and Safety of IGI, 10% With rHuPH20 in PIDD

We'll reach out to this number within 24 hrs