Phase 2/3 Study of IGSC, 20% in PIDD

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT01218438
First received: October 8, 2010
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to develop a 20% subcutaneous (SC) immunoglobulin preparation for the treatment of patients with primary immunodeficiency diseases (PIDD).


Condition Intervention Phase
Primary Immunodeficiency Diseases(PIDD)
Biological: Immune Globulin Intravenous (Human), 10% Solution
Drug: Immune Globulin Subcutaneous (Human), 20% Solution
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Clinical Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) for the Evaluation of Efficacy, Safety, Tolerability and Pharmacokinetics in Subjects With Primary Immunodeficiency Diseases (PIDD)

Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Rate of acute serious bacterial infections [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Defined as the mean number of acute serious bacterial infections per participant per year.


Secondary Outcome Measures:
  • Annual rate of all infections per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Annual rate of sinus infections per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Annual rate of fever episodes per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Annual rate of days off school/work or days unable to perform normal daily activities due to illness or infection per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Annual rate of days on antibiotics per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Annual rate of hospitalizations for illness or infection per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Annual rate of days of hospitalizations for illness or infection per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Annual rate of acute (urgent or unscheduled) physician visits, or visits to the Emergency Room for illness or infection per participant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Bioavailability of IGSC, 20% as measured by the ratio of immunoglobulin G (IgG) AUCSC (Epoch 4) to IgG AUCIV,0-τ (standardized to 1 week) (Epoch 1) adjusted for dose and dosing frequency (participants ≥12 years old) [ Time Frame: Epoch 1: 3 week IV administration interval: Week 10, 11, 12, 13. Epoch 1: 4 week IV interval: Week 9, 10, 11, 12, 13. Epoch 4 Subcutaneous administration weeks 17, 18 ] [ Designated as safety issue: No ]

    IGSC, 20% = Immune Globulin Subcutaneous (Human), 20% Solution;

    AUCSC = area under the concentration-time curve following subcutaneous administration;

    AUCIV,0-τ = area under the concentration-time curve following intravenous administration over a dosing interval


  • Trough levels of IgG (total), IgG subclasses, and specific antibodies to clinically relevant pathogens [ Time Frame: Epoch 1: 3 week IV interval- weeks 0, 1, 4, 7, 10, 13. Epoch 1: 4 week IV interval- weeks 0, 1, 5, 9, 13. Epochs 2 & 3: Subcutaneous (SC) weeks 5, 9. Epoch 4: SC weeks 1, 9, 17, 29, 40 (week dependent on time to establish "Adjusted Dose" in Epoch 2) ] [ Designated as safety issue: No ]
    Clinically relevant pathogens include Clostridium tetani (tetanus toxoid), Haemophilus influenzae type b, and Hepatitis B Virus.

  • Other pharmacokinetics parameters for IgG (total) and one specific antibody (anti- Haemophilus influenzae type b) [ Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18 ] [ Designated as safety issue: No ]
    For subjects 12 years of age or older: area under the curve over a dosing interval (AUC0-τ), clearance (CL; for IV treatment) or apparent clearance (CL/F; for SC treatment), bioavailability (F), maximum observed concentration (Cmax), minimum observed concentration (Cmin), time to Cmax (Tmax) and T1/2 (for IV only); For Children 2 to < 12 years for SC treatment in Epoch 4: area under the curve over a dosing interval (AUC0-τ), apparent clearance (CL/F), maximum observed concentration (Cmax) and minimum observed concentration (Cmin)

  • Expected trough level increase obtained in Epoch 1 compared to Epoch 2 and a nomogram or table derived from this data to be used to determine the "Individually Adapted Dose" in Epoch 4 [ Time Frame: 29 weeks ] [ Designated as safety issue: No ]
  • Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) deemed related to the investigational product per participant [ Time Frame: Up to 20 months per subject (throughout entire study) ] [ Designated as safety issue: Yes ]
    Number of related SAEs and AEs divided by number of participants

  • Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) deemed related to the investigational product per infusion [ Time Frame: Up to 20 months per subject (throughout entire study) ] [ Designated as safety issue: Yes ]
    Number of related SAEs and AEs divided by number of subjects and divided by number of infusions

  • Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) regardless of relationship to the investigational product per participant [ Time Frame: Up to 20 months per subject (throughout entire study) ] [ Designated as safety issue: Yes ]
    Number of all SAEs and AEs divided by number of participants

  • Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) regardless of relationship to the investigational product per infusion [ Time Frame: Up to 20 months per subject (throughout entire study) ] [ Designated as safety issue: Yes ]
    Number of all SAEs and AEs divided by number of infusions

  • Number of adverse events (AEs) (including and excluding infections) that begin during or within 72 hours of completion of infusion per participant [ Time Frame: Within 72 hours of completion of infusion ] [ Designated as safety issue: Yes ]
    Number of AEs that begin during or within 72 hours of completion of infusion divided by number of participants

  • Number of adverse events (AEs) (including and excluding infections) that begin during or within 72 hours of completion of infusion per infusion [ Time Frame: Within 72 hours of completion of infusion ] [ Designated as safety issue: Yes ]
    Number of AEs that begin during or within 72 hours of completion of infusion divided by the number of infusions

  • Number of adverse events (AEs) (including and excluding infections) that begin during or within 24 hours of completion of infusion per participant [ Time Frame: Within 24 hours of completion of infusion ] [ Designated as safety issue: Yes ]
    Number of AEs that begin during or within 24 hours of completion of infusion divided by number of participants

  • Number of adverse events (AEs) (including and excluding infections) that begin during or within 24 hours of completion of infusion per infusion [ Time Frame: Within 24 hours of completion of infusion ] [ Designated as safety issue: Yes ]
    Number of AEs that begin during or within 24 hours of completion of infusion divided by number of infusions

  • Number of adverse events (AEs) (including and excluding infections) that begin during or within 1 hour of completion of infusion per participant [ Time Frame: Within 1 hour of completion of infusion ] [ Designated as safety issue: Yes ]
    Number of AEs that begin during or within 1 hour of completion of infusion divided by number of participants

  • Number of adverse events (AEs) (including and excluding infections) that begin during or within 1 hour of completion of infusion [ Time Frame: Within 1 hour of completion of infusion ] [ Designated as safety issue: Yes ]
    Number of AEs that begin during or within 1 hour of completion of infusion divided by number of infusions

  • Causally related and/or temporally associated AEs per infusion [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    The total number of all AEs (including and excluding infections) that begin during infusion or within 72 hours of completion of an infusion ("temporally associated") plus the total number of AEs (including and excluding infections) starting more than 72 hours following the completion of an infusion determined by the investigator to be at least possibly related to the study drug("related"), divided by the total number of infusions

  • Proportion of infusions associated with one or more local AEs (including and excluding infections) [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: Yes ]
  • Proportion of participants reporting one or more local AEs (including and excluding infections) [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: Yes ]
  • Proportion of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped due to tolerability concerns or AEs [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: Yes ]
  • Proportion of participants for whom the infusion rate was reduced and/or the infusion was interrupted or stopped due to tolerability concerns or AEs [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: Yes ]
  • Proportion of infusions tolerated with intravenous or subcutaneous administration [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: Yes ]
  • Short term tolerance - Change in blood pressure [ Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2 ] [ Designated as safety issue: Yes ]
  • Short term tolerance - Change in heart rate (pulse) [ Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2 ] [ Designated as safety issue: Yes ]
  • Short term tolerance - Change in respiratory rate [ Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2 ] [ Designated as safety issue: Yes ]
  • Short term tolerance - Change in body temperature [ Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2 ] [ Designated as safety issue: Yes ]
  • Incidence of laboratory confirmed hemolysis that occurs following investigational product administration [ Time Frame: Epoch 1: 3 week IV interval- weeks 0, 10. Epoch 1: 4 week IV interval- weeks 0, 9. Epoch 3: Subcutaneous (SC) week 9. Epoch 4: SC weeks 17, 18, 40 ] [ Designated as safety issue: Yes ]
  • Quality of life- Pediatric Quality of Life Inventory^TM (PEDS-QL^TM) (observer: parent) for the age group 2 to 4 and 5 to 7 years [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: No ]
  • Quality of life- PEDS-QL^TM (observer: participant) for the age group 8 to 12, and 13 years (use 13 to 18 years form) [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: No ]
  • Quality of life- Short-Form 36v2 (SF-36v2) for the age group 14 years and older [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: No ]
  • Life Quality Index [ Time Frame: Up to 20 months (throughout entire study) ] [ Designated as safety issue: No ]
    For the age group 2 to 12 years the observer will be a parent, for the age group 13 years and older the observer will be the participant.

  • Treatment Satisfaction Questionnaire for Medication (TSQM) [ Time Frame: Up to 20 months per subject (throughout entire study) ] [ Designated as safety issue: No ]
    TSQM; for the age group 2 to 12 years the observer will be a parent, for the age group 13 years and older the observer will be the participant.


Enrollment: 86
Study Start Date: January 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Epochs 1-4

Epoch 1 (13 weeks): Pharmacokinetic (PK) assessment at 2nd to last infusion (in all participants ≥12 years of age). Participants will be treated intravenously once every 3 or 4 weeks at same monthly equivalent dose as prior to the study.

Epoch 2 (12-16 weeks): PK assessment (in first 15 participants ≥12 years of age) at 9th infusion to determine adjusted dose for Epoch 3 and individually adapted dose for Epoch 4. Participants will be treated subcutaneously every 7 days at a dose of IGSC, 20% that is 145% of the weekly equivalent of the IV dose in Epoch 1.

Epoch 3 (12 weeks): Participants will be treated subcutaneously every 7 days using the adjusted dose determined in Epoch 2. The individually adapted dose for use in Epoch 4 will also be determined.

Epoch 4 (40 weeks): Participants will be treated subcutaneously once every week at the individually adapted dose determined in Epoch 3. PK assessment at 17th infusion.

Biological: Immune Globulin Intravenous (Human), 10% Solution
Intravenous infusion with IGIV, 10%
Other Name: IGIV, 10%
Drug: Immune Globulin Subcutaneous (Human), 20% Solution
Subcutaneous infusion with IGSC, 20%
Other Name: IGSC, 20%

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Documented diagnosis of a form of primary humoral immunodeficiency involving defective antibody formation and requiring gammaglobulin replacement as defined according to the IUIS Scientific Committee, 2011 and by diagnostic criteria according to Conley et al. (1999). The diagnosis must be confirmed by the Medical Director prior to first treatment with the investigational product (IP) in the study.
  • Participant is 2 years or older at the time of screening, and has a minimum body weight of 13 kg.
  • Written informed consent has been obtained from either the participant or the participant's legally authorized representative prior to any study-related procedures and study product administration
  • Participant has been receiving a stable monthly equivalent dose of IgG at an average minimum dose equivalent to 300 mg/kg bodyweight (BW)/4 weeks and a maximum dose equivalent to 1.0 gram/kg BW/4 weeks, for a minimum of 12 weeks prior to first treatment with the IP in the study.
  • Serum trough level of IgG > 500 mg/dL at screening
  • Participant is willing and able to comply with the requirements of the protocol

Main Exclusion Criteria:

  • Participant has 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/mm^3)
  • Creatinine clearance (CLcr) value that is < 60% of normal for age and gender either measured, or calculated according to the Cockcroft-Gault formula
  • 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
  • Participant is receiving anti-coagulation therapy (low dose aspirin at ≤325 mg/day is permitted) or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) or sickle cell disease with crisis within 12 months prior to screening or a history of thrombophilia
  • Abnormal protein loss (protein losing enteropathy, nephrotic syndrome)
  • Anemia that would preclude phlebotomy for laboratory studies according to standard practice at the site
  • Acute serious bacterial infection within 3 months prior to screening
  • Ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following intravenous immunoglobulin, subcutaneous immunoglobulin, and/or Immune Serum Globulin (ISG) infusions
  • Severe immunoglobulin A (IgA) deficiency (less than 0.07g/L) with known anti-IgA antibodies and a history of hypersensitivity
  • Participant is on continuous systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and, in the opinion of the investigator, cannot stop these for the duration of the study without putting the patient at risk of increased infections
  • Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening
  • Bleeding disorder or thrombocytopenia with 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 subcutaneous therapy
  • Total protein > 9 g/dL or myeloma or macroglobulinemia (IgM) or paraproteinemia
  • Severe dermatitis that would preclude adequate sites for safe product administration
  • Women of childbearing potential meeting any one of the following criteria:

    • Participant presents with a positive pregnancy test
    • Participant is breast feeding
    • Participant intends to begin nursing during the course of the study
    • Participant 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
  • Participation in another clinical study and exposure to an investigational product or device within 30 days prior to study enrollment (exception: treatment in a previous Baxter immunoglobulin study)
  • Participant is scheduled to participate in another (non-Baxter) non-observational (interventional) clinical study involving an investigational product or device during the course of the study
  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: NCT01218438

Locations
United States, California
University of California, Irvine
Irvine, California, United States, 92697
United States, Colorado
IMMUNOe International Research Centers
Centennial, Colorado, United States, 80112
United States, Florida
Allergy Associates of the Palm Beaches
North Palm Beach, Florida, United States, 33408
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kentucky
Family Allergy and Asthma Research Institute
Louisville, Kentucky, United States, 40215
United States, Louisiana
Children's Hospital New Orleans- LSUHSC School of Medicine
New Orleans, Louisiana, United States, 70118
United States, Minnesota
Midwest Immunology Clinical and Infusion Center
Plymouth, Minnesota, United States, 55446
United States, Missouri
SSM Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States, 63104
United States, New York
Montefiore Medical Center Division of Allergy/Immunology
Bronx, New York, United States, 10461
United States, Oklahoma
Oklahoma Institute of Allergy and Asthma Clinical Research
Oklahoma City, Oklahoma, United States, 73131
Vital Prospects Clinical Research Institute, PC
Tulsa, Oklahoma, United States, 74136
United States, Texas
Dallas Allergy Immunology Research
Dallas, Texas, United States, 75230
Allergy Asthma and Immunology Clinic PA
Irving, Texas, United States, 75063
United States, Utah
Rocky Mountain Asthma/Allergy/Immunology
Layton, Utah, United States, 84041
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Quebec
Centre Hospitalier Universitaire (CHU) Sainte-Justine
Montreal, Quebec, Canada, H3H 1C5
Montreal Children's Hospital- McGill University health Center
Montreal, Quebec, Canada, HEH 1P3
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Richard Schiff, MD Baxter Healthcare Corporation
  More Information

Publications:
Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT01218438     History of Changes
Other Study ID Numbers: 170904
Study First Received: October 8, 2010
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Pharmaceutical Solutions
Rho(D) Immune Globulin
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014