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Immune Globulin Subcutaenous (Human), 20%

Primary Purpose

Primary Immunodeficiency Diseases (PID)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Immune Globulin Subcutaneous (Human), 20%
Immune Globulin Intravenous (Human), 10%
Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)
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)

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 antibody formation and requiring gammaglobulin replacement, as defined according to the IUIS Scientific Committee 2009, and by diagnostic criteria according to Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Clin Immunol 1999; 93:190-197. The diagnosis must be confirmed 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 IgG over a period of at least 3 months prior to screening at an average minimum dose over that interval equivalent to 300 mg/kg body weight (BW)/4 weeks and a maximum dose equivalent to 1.0 gram/kg BW/4 weeks at a dosing frequency as follows:

    1. intravenously (IV) at mean intervals of approximately 3 or 4 weeks or
    2. subcutaneously (SC) at mean intervals of approximately 1 or 2 weeks
  • 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
  • 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):

    1. Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
    2. 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
  • 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 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 subcutaneous 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

    1. subject presents with a positive pregnancy test
    2. subject is breast feeding
    3. subject intends to begin nursing during the course of the study
    4. 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) non-observational (interventional) 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

  • Medizinische Universität Wien / AHK Wien (General Hospital Vienna), Universitätsklinik für Kinder- und Jugendheilkunde
  • Universitätsklinikum Erlangen, Medizinische Klinik 3
  • University Medical Centre Freiburg, Centre of Chronic Immunodeficiency, Divison of Rheumatology and Clinical Immunology
  • Universitätsklinikum Hamburg-Eppendorf, Kinderklinik
  • Medizinische Hochschule Hannover, Klinik für Immunologie und Rheumatologie
  • Klinikum St. Georg GmbH, Klinik für Kinder- und Jugendmedizin
  • Fővárosi Önkormányzat Egyesített Szent István és Szent László Kórház, Gyermekhematológiai és Őssejt-transzplantációs Osztály
  • University of Debrecen, Medical and Health Science Center, Department of Infectious and Pediatric Immunology
  • The Queen Silvia Children´s Hospital
  • Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Immunology Department
  • Addenbrooke´s Hospital, Department of Clinical Immunology
  • Royal London Hospital, Barts and the London NHS Trust, Department of Immunology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Epoch 1 (intravenous pre-study treatment) + Epoch 2

Epoch 1 (subcutaneous pre-study treatment) + Epoch 2

Arm Description

Study Epoch 1 (13 weeks): treatment with KIOVIG (once every 3 or 4 weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents)

Study Epoch 1 (12 weeks): treatment with SUBCUVIA (once every week or once every two weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents)

Outcomes

Primary Outcome Measures

Acute serious bacterial infection rate defined as the mean number of acute serious bacterial infections per subject per year in the intent-to-treat population
Acute serious bacterial infections will include bacteremia / sepsis, bacterial meningitis, osteomyelitis / septic arthritis, bacterial pneumonia, and visceral abscess, diagnosed according to the Diagnostic Criteria for Serious Acute Bacterial Infections

Secondary Outcome Measures

Full Information

First Posted
August 8, 2011
Last Updated
April 30, 2021
Sponsor
Baxalta now part of Shire
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1. Study Identification

Unique Protocol Identification Number
NCT01412385
Brief Title
Immune Globulin Subcutaenous (Human), 20%
Official Title
A Clinical Study of Immune Globulin Subcutaneous (Human) (IGSC), 20% for the Evaluation of Efficacy, Safety, and Pharmacokinetics in Subjects With Primary Immunodeficiency Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
June 20, 2011 (Actual)
Primary Completion Date
May 13, 2014 (Actual)
Study Completion Date
May 13, 2014 (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 develop a 20% subcutaneous immunoglobulin treatment option for patients with primary immunodeficiency (PID) diseases.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Epoch 1 (intravenous pre-study treatment) + Epoch 2
Arm Type
Experimental
Arm Description
Study Epoch 1 (13 weeks): treatment with KIOVIG (once every 3 or 4 weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents)
Arm Title
Epoch 1 (subcutaneous pre-study treatment) + Epoch 2
Arm Type
Experimental
Arm Description
Study Epoch 1 (12 weeks): treatment with SUBCUVIA (once every week or once every two weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents)
Intervention Type
Biological
Intervention Name(s)
Immune Globulin Subcutaneous (Human), 20%
Other Intervention Name(s)
IGSC, 20%
Intervention Description
Subcutaneous infusion (regulated via a pump), Epoch 2 only (all subjects)
Intervention Type
Biological
Intervention Name(s)
Immune Globulin Intravenous (Human), 10%
Other Intervention Name(s)
GAMMAGARD LIQUID (tradename in the US and Canada), KIOVIG (trademark in Europe)
Intervention Description
Intravenous infusion (regulated via a pump)
Intervention Type
Biological
Intervention Name(s)
Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)
Other Intervention Name(s)
SUBCUVIA
Intervention Description
Subcutaneous infusion (regulated via a pump)
Primary Outcome Measure Information:
Title
Acute serious bacterial infection rate defined as the mean number of acute serious bacterial infections per subject per year in the intent-to-treat population
Description
Acute serious bacterial infections will include bacteremia / sepsis, bacterial meningitis, osteomyelitis / septic arthritis, bacterial pneumonia, and visceral abscess, diagnosed according to the Diagnostic Criteria for Serious Acute Bacterial Infections
Time Frame
1 year

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 antibody formation and requiring gammaglobulin replacement, as defined according to the IUIS Scientific Committee 2009, and by diagnostic criteria according to Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Clin Immunol 1999; 93:190-197. The diagnosis must be confirmed 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 IgG over a period of at least 3 months prior to screening at an average minimum dose over that interval equivalent to 300 mg/kg body weight (BW)/4 weeks and a maximum dose equivalent to 1.0 gram/kg BW/4 weeks at a dosing frequency as follows: intravenously (IV) at mean intervals of approximately 3 or 4 weeks or subcutaneously (SC) at mean intervals of approximately 1 or 2 weeks 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 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 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 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 subcutaneous 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) non-observational (interventional) 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
Medizinische Universität Wien / AHK Wien (General Hospital Vienna), Universitätsklinik für Kinder- und Jugendheilkunde
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Universitätsklinikum Erlangen, Medizinische Klinik 3
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
University Medical Centre Freiburg, Centre of Chronic Immunodeficiency, Divison of Rheumatology and Clinical Immunology
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf, Kinderklinik
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Medizinische Hochschule Hannover, Klinik für Immunologie und Rheumatologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Klinikum St. Georg GmbH, Klinik für Kinder- und Jugendmedizin
City
Leipzig
ZIP/Postal Code
04129
Country
Germany
Facility Name
Fővárosi Önkormányzat Egyesített Szent István és Szent László Kórház, Gyermekhematológiai és Őssejt-transzplantációs Osztály
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
University of Debrecen, Medical and Health Science Center, Department of Infectious and Pediatric Immunology
City
Debrecen
ZIP/Postal Code
4012
Country
Hungary
Facility Name
The Queen Silvia Children´s Hospital
City
Gothenburg
ZIP/Postal Code
416 85
Country
Sweden
Facility Name
Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Immunology Department
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Addenbrooke´s Hospital, Department of Clinical Immunology
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Royal London Hospital, Barts and the London NHS Trust, Department of Immunology
City
London
ZIP/Postal Code
E1 2ES
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
27613250
Citation
Borte M, Krivan G, Derfalvi B, Marodi L, Harrer T, Jolles S, Bourgeois C, Engl W, Leibl H, McCoy B, Gelmont D, Yel L. Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies. Clin Exp Immunol. 2017 Jan;187(1):146-159. doi: 10.1111/cei.12866. Epub 2016 Oct 18.
Results Reference
result
PubMed Identifier
34036490
Citation
Li Z, McCoy B, Engl W, Yel L. Steady-State Serum IgG Trough Levels Are Adequate for Pharmacokinetic Assessment in Patients with Immunodeficiencies Receiving Subcutaneous Immune Globulin. J Clin Immunol. 2021 Aug;41(6):1331-1338. doi: 10.1007/s10875-021-00990-z. Epub 2021 May 26.
Results Reference
derived
PubMed Identifier
31268374
Citation
Suez D, Krivan G, Jolles S, Stein M, Gupta S, Paris K, van Hagen PM, Brodszki N, Engl W, Leibl H, McCoy B, Yel L. Safety and tolerability of subcutaneous immunoglobulin 20% in primary immunodeficiency diseases from two continents. Immunotherapy. 2019 Aug;11(12):1057-1065. doi: 10.2217/imt-2019-0057. Epub 2019 Jul 3.
Results Reference
derived
PubMed Identifier
30626238
Citation
Paris K, Haddad E, Borte M, Brodszki N, Derfalvi B, Marodi L, Hussain I, Darter A, Engl W, Leibl H, McCoy B, Yel L. Tolerability of subcutaneous immunoglobulin 20%, Ig20Gly, in pediatric patients with primary immunodeficiencies. Immunotherapy. 2019 Apr;11(5):397-406. doi: 10.2217/imt-2018-0088. Epub 2019 Jan 9.
Results Reference
derived

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Immune Globulin Subcutaenous (Human), 20%

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