A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID)

Baxalta now part of Shire17 enrolled

Overview

In this study, Japanese participants with primary immunodeficiency diseases were treated with Immune Globulin Subcutaneous (Human), 20% solution, (IGSC, 20%). This study will be in 3 parts: Part 1: Infusions with Immunoglobulin Intravenous (IGIV) every 3 or 4 weeks for 13 weeks. Part 2: Participants will switch to weekly subcutaneous infusions with IGSC, 20% for 24 weeks. Part 3: A subset will receive biweekly subcutaneous infusions with IGSC, 20% for 12 weeks. The main aim of the study is to assess base levels of Immunoglobulin globulin G (IgG) levels in the blood of the participants after weekly and biweekly treatment with IGSC, 20% (in Parts 2 and 3 of the study). Their PID will be treated by their doctor according to their doctor's usual clinical practice.

This study consists of 3 treatment parts (Epoch 1, 2, 3). The total evaluation period of the study will be 57 weeks in which screening period is for 2-8 weeks and Epoch 1 is from Week 8 to Week 21, Epoch 2 is from Week 21 to Week 45, Epoch 3 is from Week 45 to Week 57. Each participant will receive IGIV treatment in Epoch 1 for a total of 13 weeks, then switch to weekly subcutaneous (SC) treatment with IGSC, 20% in Epoch 2 for a total of 24 weeks and will continue into Epoch 3 for a total of 12 weeks of biweekly SC treatment with IGSC, 20%. Drug dose in Epoch 2 and Epoch 3 will be adjusted so that it will be an equivalent weekly dose of the dose administered in Epoch 1 and twice the dose administrated in Epoch 2 respectively. Epoch 2 will contain two periods, period 1: dose adjustment period (first 12 weeks) and period 2: evaluation period (second 12 weeks).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents. * Participants must have a documented diagnosis of a form of primary humoral immunodeficiency involving antibody formation and requiring gammaglobulin replacement. The diagnosis must be confirmed by the medical director prior to treatment with IGIV. * Participant is 2 years or older at the time of screening. * Written informed consent is obtained from either the participants or the participants legally authorized representative prior to any study-related procedures and study product administration. * Participant has been receiving a consistent dose of IGIV over a period of at least 3 months prior to screening equivalent to approximately 200-600 mg/kg-body weight (BW) per 3- 4 week period, as according to the product package insert * Participant has a serum trough level of IgG \>= 5 gram per liter (g/L) at screening. * Participant has not had a serious bacterial infection within the 3 months prior to screening. * Participant is willing and able to comply with the requirements of the protocol. Exclusion Criteria: * Participant 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 (ULN) for the testing laboratory * Persistent severe neutropenia (defined as an absolute neutrophil count \[ANC\] \<= 500/milli cubic meter \[mm\^3\]). * Participant has presence of renal function impairment defined by estimated glomerular filtration rate (eGFR) is \<60 milliliter per minute/ 1.73 square meter (mL/min/1.73m\^2). * Participant 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. * Participant 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. * Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome). * Participant has anemia that would preclude phlebotomy for laboratory studies according to standard practice at the site. * Participant 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. * Participant has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L), known anti IgA antibodies, and a history of hypersensitivity. * Participant 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. * Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening. * Participant has a bleeding disorder, or a platelet count less than 20,000/ microliter (mcL), or, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of subcutaneous therapy. * Participant has total protein \> 9 gram per deciliter (g/dL) or myeloma, or macroglobulinemia (IgM) or paraproteinemia. * 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. * Participant has participated in another clinical study and has been exposed to an IP or device within 30 days prior to study enrollment. * Participant is scheduled to participate in another non-observational (interventional) clinical study involving an IP or device during the course of the study. * Participant has severe dermatitis that would preclude adequate sites for safe product administration.

Locations (8)

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Kyushu University Hospital

Fukuoka, Fukuoka, Japan

Kurume University Hospital

Kurume-shi, Fukuoka, Japan

Gifu University Hospital

Gifu, Gifu, Japan

Hiroshima University Hospital

Hiroshima, Hiroshima, Japan

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

National Defense Medical College Hospital

Tokorozawa-shi, Saitama, Japan

Tokyo Medical Dental University Hospital

Bunkyo-ku, Tokyo, Japan

Outcomes

Primary Outcomes

Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2

Total serum trough levels of IgG antibodies measured during period 2 of Epoch 2 were assessed.

Time frame: Epoch 2 (period 2): Up to 24 weeks

Epoch 3: Total Serum Trough Levels of IgG Antibodies

Total serum trough levels of IgG antibodies measured during Epoch 3 were assessed.

Time frame: Epoch 3: Up to Week 12

Secondary Outcomes

Epoch 1: Total Serum Trough Levels of IgG Antibodies

Total serum trough levels of IgG antibodies measured during Epoch 1 were assessed.

Time frame: Epoch 1: Up to Week 13

Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG

Time frame: Epoch 2: Week 21

Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses

Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.

Time frame: Epoch 2: Week 21

Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG

Time frame: Epoch 2: Week 21

Epoch 2: CL/F for Total Serum Levels of IgG Subclasses

Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.

Time frame: Epoch 2: Week 21

Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG

Time frame: Epoch 2: Week 21

Epoch 2: Cmax for Total Serum Levels of IgG Subclasses

Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.

Time frame: Epoch 2: Week 21

Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG

Time frame: Epoch 2: Week 21

Epoch 2: Cmin for Total Serum Levels of IgG Subclasses

Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.

Time frame: Epoch 2: Week 21

Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG

Time frame: Epoch 2: Week 21

Epoch 2: Tmax for Total Serum Levels of IgG Subclasses

Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.

Time frame: Epoch 2: Week 21

Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)

Trough levels of specific antibodies to clinically relevant pathogen (Clostridium tetani toxoid and HBV) were assessed in Epoch 1, Epoch 2 and Epoch 3. Data was analyzed per interval in each Epoch for this outcome measure.

Time frame: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)

Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)

Trough levels of specific antibodies to clinically relevant pathogens (HIB) were assessed in Epoch 1, Epoch 2, and Epoch 3. Data was analyzed per interval in each Epoch for this outcome measure.

Time frame: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)

Health Related Quality of Life: Treatment Preference

Treatment preference questionnaire is a self-administered questionnaire developed to assess participants' preference towards the administration of new IGSC therapy. There are 4-items on the questionnaire, which investigate a participant's preference on the clinic/hospital/home setting of receiving the immunoglobulin therapy, the participant's rating on the frequency and method of administration, and the participant's preference to continue receiving the IGSC treatment. The questionnaire included following categories: Where do you prefer to receive your immunoglobulin therapy, The frequency of administration, as pre-specified in protocol, data is reported as per age (2-13 years and \>=14 years).

Time frame: Up to approximately 1.5 years

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

TEAEs was defined as adverse events (AEs) with onset after date-time of first dose of study drug, or medical conditions present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Any TEAE that is recorded by the investigator as "possibly related" or "probably related" to IP was considered as IGSC, 20%-related AE, and any AE recorded as "unlikely related" or "not related" was considered as unrelated AE. AEs included vital signs, clinical laboratory measurements.