Immune Globulin Subcutaenous (Human), 20%

Sponsor

Baxalta now part of Shire (Industry)

Overall Status

Completed

CT.gov ID

NCT01412385

Collaborator

(none)

Enrollment

Locations

Arms

34.8

Actual Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Immunodeficiency Diseases (PID)	Biological: Immune Globulin Subcutaneous (Human), 20% Biological: Immune Globulin Intravenous (Human), 10% Biological: Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 20, 2011

Actual Primary Completion Date :

May 13, 2014

Actual Study Completion Date :

May 13, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Epoch 1 (intravenous pre-study treatment) + Epoch 2 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% Subcutaneous infusion (regulated via a pump), Epoch 2 only (all subjects) Other Names: IGSC 20% Biological: Immune Globulin Intravenous (Human), 10% Intravenous infusion (regulated via a pump) Other Names: GAMMAGARD LIQUID (tradename in the US and Canada) KIOVIG (trademark in Europe)
Experimental: Epoch 1 (subcutaneous pre-study treatment) + Epoch 2 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% Subcutaneous infusion (regulated via a pump), Epoch 2 only (all subjects) Other Names: IGSC 20% Biological: Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin) Subcutaneous infusion (regulated via a pump) Other Names: SUBCUVIA

Arm

Intervention/Treatment

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

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%

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

Other Names:

IGSC

20%

Biological: Immune Globulin Intravenous (Human), 10%

Intravenous infusion (regulated via a pump)

Other Names:

GAMMAGARD LIQUID (tradename in the US and Canada)

KIOVIG (trademark in Europe)

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

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%

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

Other Names:

IGSC

20%

Biological: Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)

Subcutaneous infusion (regulated via a pump)

Other Names:

SUBCUVIA

Outcome Measures

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 [1 year]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts 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:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Medizinische Universität Wien / AHK Wien (General Hospital Vienna), Universitätsklinik für Kinder- und Jugendheilkunde	Vienna	Austria	1090
2	Universitätsklinikum Erlangen, Medizinische Klinik 3	Erlangen	Germany	91054
3	University Medical Centre Freiburg, Centre of Chronic Immunodeficiency, Divison of Rheumatology and Clinical Immunology	Freiburg	Germany	79106
4	Universitätsklinikum Hamburg-Eppendorf, Kinderklinik	Hamburg	Germany	20246
5	Medizinische Hochschule Hannover, Klinik für Immunologie und Rheumatologie	Hannover	Germany	30625
6	Klinikum St. Georg GmbH, Klinik für Kinder- und Jugendmedizin	Leipzig	Germany	04129
7	Fővárosi Önkormányzat Egyesített Szent István és Szent László Kórház, Gyermekhematológiai és Őssejt-transzplantációs Osztály	Budapest	Hungary	1097
8	University of Debrecen, Medical and Health Science Center, Department of Infectious and Pediatric Immunology	Debrecen	Hungary	4012
9	The Queen Silvia Children´s Hospital	Gothenburg	Sweden	416 85
10	Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Immunology Department	Birmingham	United Kingdom	B9 5SS
11	Addenbrooke´s Hospital, Department of Clinical Immunology	Cambridge	United Kingdom	CB2 2QQ
12	Royal London Hospital, Barts and the London NHS Trust, Department of Immunology	London	United Kingdom	E1 2ES