Immune Globulin Subcutaenous (Human), 20%

NCT01412385 | Completed Phase 2

• 2 other identifiers: 1709032010-019459-23
• Study Type: interventional
• Target: 55
• Locations: 5 countries
• Sites: 12

Brief Summary

The purpose of the study is to develop a 20% subcutaneous immunoglobulin treatment option for patients with primary immunodeficiency (PID) diseases.

Conditions

Primary Immunodeficiency Diseases (PID)

Outcome Measures

Primary Outcomes (1)

• 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

  1 year

Study Arms (2)

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

EXPERIMENTAL

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)

Biological: Immune Globulin Subcutaneous (Human), 20%; Biological: Immune Globulin Intravenous (Human), 10%

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

EXPERIMENTAL

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)

Biological: Immune Globulin Subcutaneous (Human), 20%; Biological: Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)

Interventions

Immune Globulin Subcutaneous (Human), 20% BIOLOGICAL

Subcutaneous infusion (regulated via a pump), Epoch 2 only (all subjects)

Also known as: IGSC, 20%

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

Immune Globulin Intravenous (Human), 10% BIOLOGICAL

Intravenous infusion (regulated via a pump)

Also known as: GAMMAGARD LIQUID (tradename in the US and Canada), KIOVIG (trademark in Europe)

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

Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin) BIOLOGICAL

Subcutaneous infusion (regulated via a pump)

Also known as: SUBCUVIA

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

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (12)

Medizinische Universität Wien / AHK Wien (General Hospital Vienna), Universitätsklinik für Kinder- und Jugendheilkunde

Vienna, 1090, Austria

Location

Universitätsklinikum Erlangen, Medizinische Klinik 3

Erlangen, 91054, Germany

Location

University Medical Centre Freiburg, Centre of Chronic Immunodeficiency, Divison of Rheumatology and Clinical Immunology

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Kinderklinik

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover, Klinik für Immunologie und Rheumatologie

Hanover, 30625, Germany

Location

Klinikum St. Georg GmbH, Klinik für Kinder- und Jugendmedizin

Leipzig, 04129, Germany

Location

Fővárosi Önkormányzat Egyesített Szent István és Szent László Kórház, Gyermekhematológiai és Őssejt-transzplantációs Osztály

Budapest, 1097, Hungary

Location

University of Debrecen, Medical and Health Science Center, Department of Infectious and Pediatric Immunology

Debrecen, 4012, Hungary

Location

The Queen Silvia Children´s Hospital

Gothenburg, 416 85, Sweden

Location

Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Immunology Department

Birmingham, B9 5SS, United Kingdom

Location

Addenbrooke´s Hospital, Department of Clinical Immunology

Cambridge, CB2 2QQ, United Kingdom

Location

Royal London Hospital, Barts and the London NHS Trust, Department of Immunology

London, E1 2ES, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 27613250 RESULT

• 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.

  PMID: 34036490 DERIVED

• 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.

  PMID: 31268374 DERIVED

• 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.

  PMID: 30626238 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

gamma-Globulins; Patents as Topic

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Intellectual Property; Jurisprudence; Social Control, Formal; Health Care Economics and Organizations

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2011
• First Posted: August 9, 2011
• Study Start: June 20, 2011
• Primary Completion: May 13, 2014
• Study Completion: May 13, 2014
• Last Updated: May 5, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

DE (5); SE (1); HU (2); AU (1); GB (3)