Immune Globulin Subcutaenous (Human), 20%

Condition(s) targeted: Primary Immunodeficiency Diseases (PID)

Intervention: Immune Globulin Subcutaneous (Human), 20% (Biological); Immune Globulin Intravenous (Human), 10% (Biological); Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin) (Biological)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Baxalta US Inc.

Official(s) and/or principal investigator(s):
Leman Yel, MD, Study Director, Affiliation: Baxter Healthcare Corporation

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

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 design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Minimum age: 2 Years. Maximum age: N/A. Gender(s): Both.

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: 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

Medizinische Universität Wien / AHK Wien (General Hospital Vienna), Universitätsklinik für Kinder- und Jugendheilkunde, Vienna 1090, Austria

Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen 91054, Germany

University Medical Centre Freiburg, Centre of Chronic Immunodeficiency, Divison of Rheumatology and Clinical Immunology, Freiburg 79106, Germany

Universitätsklinikum Hamburg-Eppendorf, Kinderklinik, Hamburg 20246, Germany

Medizinische Hochschule Hannover, Klinik für Immunologie und Rheumatologie, Hannover 30625, Germany

Klinikum St. Georg GmbH, Klinik für Kinder- und Jugendmedizin, Leipzig 04129, Germany

Fővárosi Önkormányzat Egyesített Szent István és Szent László Kórház, Gyermekhematológiai és Őssejt-transzplantációs Osztály, Budapest 1097, Hungary

University of Debrecen, Medical and Health Science Center, Department of Infectious and Pediatric Immunology, Debrecen 4012, Hungary

The Queen Silvia Children´s Hospital, Gothenburg 416 85, Sweden

Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Immunology Department, Birmingham B9 5SS, United Kingdom

Addenbrooke´s Hospital, Department of Clinical Immunology, Cambridge CB2 2QQ, United Kingdom

Royal London Hospital, Barts and the London NHS Trust, Department of Immunology, London E1 2ES, United Kingdom

Starting date: August 2011
Last updated: June 26, 2015