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

A Phase 3, Open-label, Non-controlled, Multi-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Subjects With Primary Immunodeficiency Diseases (PID)

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).

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.