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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxalta US Inc.
ClinicalTrials.gov Identifier:
NCT01485796
First received: December 2, 2011
Last updated: May 4, 2017
Last verified: March 2017
  Purpose

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.


Condition Intervention Phase
Primary Immunodeficiency Disorders Biological: Immune Globulin Infusion (Human), 10% Biological: Recombinant human hyaluronidase Phase 2 Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Baxalta US Inc.:

Primary Outcome Measures:
  • Number of Related Systemic Adverse Events (Excluding Infections) [ Time Frame: 7 months (per subject) ]
  • Rate of Related Systemic Adverse Events (Excluding Infections) Per Infusion [ Time Frame: 7 months (per subject) ]
    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 [ Time Frame: 6 months (per subject) ]
  • 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) ]
  • Number of Related Local Adverse Events (Excluding Infections) [ Time Frame: 7 months (per subject) ]
  • Rate of Related Local Adverse Events (Excluding Infections) Per Infusion [ Time Frame: 7 months (per subject) ]
    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) [ Time Frame: 7 months (per subject) ]
  • Rate of All Adverse Events (Excluding Infections) Per Infusion [ Time Frame: 7 months (per subject) ]
    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 [ Time Frame: 7 months (per subject) ]
  • Trough Levels of Immunoglobulin G (IgG) [ Time Frame: 7 months (per subject) ]
    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 [ Time Frame: 7 months (per subject) ]
    Non-parametric descriptive statistics (median, range) are provided.

  • Number of Infusion Sites (Needle Sticks) Per Month in Epoch 1 and Epoch 2 [ Time Frame: 7 months (per subject) ]
    Non-parametric descriptive statistics (median, range) are provided.

  • Duration of Infusion in Epoch 1 and Epoch 2 [ Time Frame: 7 months (per subject) ]
    Non-parametric descriptive statistics (median, range) are provided.

  • Maximum Infusion Rate in Epoch 1 and Epoch 2 [ Time Frame: 7 months (per subject) ]
    Non-parametric descriptive statistics (median, range) are provided.

  • Number of Weeks to Reach Final 3 or 4-week Dose Interval [ Time Frame: 7 months (per subject) ]
    Non-parametric descriptive statistics (median, range) are provided.


Enrollment: 54
Study Start Date: December 1, 2011
Study Completion Date: January 1, 2013
Primary Completion Date: January 1, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Epoch 1 and Epoch 2
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.
Biological: Immune Globulin Infusion (Human), 10%
Subcutaneous administration will be used in Study Epochs 1 and 2.
Other Names:
  • IGI
  • 10%
Biological: Recombinant human hyaluronidase
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.
Other Name: rHuPH20

  Eligibility

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485796

Locations
United States, California
University of California, Irvine
Irvine, California, United States, 92697
United States, Colorado
IMMUNOe International Research Centers
Thornton, Colorado, United States, 80233
United States, Florida
Allergy Associates of the Palm Beaches, PA
North Palm Beach, Florida, United States, 33408
United States, Louisiana
LSU Health Sciences Center & Children´s Hospital
New Orleans, Louisiana, United States, 70118
United States, Minnesota
Midwest Immunology
Plymouth, Minnesota, United States, 55446
United States, Nebraska
Midlands Pediatrics PC
Papillion, Nebraska, United States, 68046
United States, New York
Winthrop Allergy and Immunology
Mineola, New York, United States, 11501
United States, Oklahoma
Oklahoma Institute of Allergy & Asthma Clinical Research
Oklahoma City, Oklahoma, United States, 73131
United States, Pennsylvania
Allergy and Clinical Immunology Associates
Pittsburgh, Pennsylvania, United States, 15241
United States, Texas
Allergy, Asthma & Immunology Clinic PA
Irving, Texas, United States, 75063
Sponsors and Collaborators
Baxalta US Inc.
Investigators
Study Director: Leman Yel, MD Baxalta US Inc., now part of Shire
  More Information

Responsible Party: Baxalta US Inc.
ClinicalTrials.gov Identifier: NCT01485796     History of Changes
Other Study ID Numbers: 161101
Study First Received: December 2, 2011
Results First Received: March 10, 2017
Last Updated: May 4, 2017

Keywords provided by Baxalta US Inc.:
PIDD

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 28, 2017