A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
Condition: Primary Immunodeficiency
MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes
Intervention: IGSC 20%
Intervention description: SC infusion pump.
Intervention MeSH terms: Immunoglobulins; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: Single sequence crossover design
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 6 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Immunologic Deficiency Syndromes; Immune System Diseases; Immunoglobulins

Summary:

      The purpose of the study is to determine whether biweekly (every 2 weeks) administration of
      Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%)
      produces a steady-state area under the concentration versus time curve (AUC) of total
      Immunoglobulin G (IgG) that is non-inferior to that produced by weekly administration of IGSC
      20% in treatment-experienced participants with primary immunodeficiency (PI).
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion Criteria only for Treatment-Experienced Participants

          -  Participants 18 years to 75 years (inclusive) at screening

          -  Participants with documented and confirmed pre-existing diagnosis of Primary
             Immunodeficiency (PI) with features of hypogammaglobulinemia requiring Immunoglobulin
             G (IgG) replacement therapy including but not limited to the following humoral-based
             immunodeficiency syndromes (example, X-linked agammaglobulinemia, common variable
             immunodeficiency), and combined immunodeficiency syndromes without lymphocytopenia
             (example, hyper immunoglobulin M immunodeficiency syndrome).

          -  Participants have not had an Serious bacterial infection (SBI) or been hospitalized
             for infection of any etiology (example, viral, fungal, parasitic) within the last 3
             months prior to screening or during screening.

          -  Participants currently receiving IgG replacement therapy for ≥3 months via Intravenous
             (IV) or SC infusion. Participants receiving IVIG prior to study must receive a dosage
             of at least 200 mg/kg per infusion.

          -  Participants whose screening IgG trough levels must be ≥500 milligram per deciliter
             (mg/dL).

          -  Participants have signed an informed consent form.

        Inclusion Criteria only for Treatment-Naïve Participants

          -  Participants 6 years to 75 years (inclusive) at screening.

          -  Participants with documented and confirmed diagnosis of PI with features of
             hypogammaglobulinemia requiring IgG replacement therapy including but not limited to
             the following humoral-based immunodeficiency syndromes (example, X-linked
             agammaglobulinemia, common variable immunodeficiency), and combined immunodeficiency
             syndromes without lymphocytopenia (example, hyper immunoglobulin M immunodeficiency
             syndrome).

          -  Participants have never received IgG replacement treatment (ie, no prior immune
             globulin replacement therapy).

          -  Participants whose screening IgG level must be ≤400 mg/dL.

          -  Participants do not have an SBI nor requires hospitalization for infection of any
             etiology (example, viral, fungal, parasitic) during screening or at baseline.

          -  Participants have signed an informed consent.

        Exclusion Criteria:

          -  Participants with clinical evidence of any significant acute or chronic disease that,
             in the opinion of the investigator, may interfere with successful completion of the
             trial or place the participant at undue medical risk.

          -  Participants have had a known serious adverse reaction (AR) to immunoglobulin or any
             anaphylactic reaction to blood or any blood-derived product.

          -  Participants who have a history of blistering skin disease, clinically significant
             thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections, or other
             disorders where SC therapy would be contraindicated during the study.

          -  Participants have known isolated IgG subclass deficiency; isolated specific antibody
             deficiency (SAD) or selective IgG deficiency; or transient hypogammaglobulinemia of
             infancy.

          -  Participants have known Selective Immunoglobulin A (IgA) Deficiency (with or without
             antibodies to IgA).

          -  Participants have significant proteinuria (≥3+ or known urinary protein loss >1 gram
             g/24 hours or nephrotic syndrome), has acute renal failure, is on dialysis, and/or has
             severe renal impairment on Screening laboratory testing (blood urea nitrogen [BUN] or
             creatinine more than 2.5 times the upper limit of normal [ULN]).

          -  Participants have screening values of aspartate aminotransferase (AST) or alanine
             aminotransferase (ALT) levels exceeding more than 2.5 times the ULN for the expected
             normal range for the testing laboratory.

          -  Participants have hemoglobin <9 gram per deciliter (g/dL) at screening.

          -  Participants have a history (either 1 episode within the year prior to the Screening
             Visit or 2 previous episodes over a lifetime) of or current diagnosis of
             thromboembolism (example, myocardial infarction, cerebrovascular accident or transient
             ischemic attack) or deep venous thrombosis.

          -  Participants are currently receiving anti-coagulation therapy which would make SC
             administration inadvisable (vitamin K antagonists, nonvitamin K antagonist oral
             anticoagulants [example, dabigatran etexilate targeting Factor IIa, rivaroxaban,
             edoxaban, and apixaban targeting Factor Xa], and parenteral anticoagulants [example,
             fondaparinux]).

          -  Participants currently have a known hyperviscosity syndrome.

          -  Participants have an acquired medical condition that is known to cause secondary
             immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma,
             chronic or recurrent neutropenia (absolute neutrophil count less than 1000/microliter
             (μL) [1.0 x10^9/L]), or human immunodeficiency virus infection/acquired immune
             deficiency syndrome.

          -  Participants have a known previous infection with or clinical signs and symptoms
             consistent with current hepatitis B virus or hepatitis C virus infection.

          -  Participants are receiving any of the following medications: (a) immunosuppressants
             including chemotherapeutic agents; (b) immunomodulators; (c) long-term systemic
             corticosteroids defined as daily dose >1 mg of prednisone equivalent/kg/day for >30
             days. Note: Intermittent courses of corticosteroids of not more than 10 days would not
             exclude a participant. Inhaled or topical corticosteroids are allowed.

          -  Participants (if <18 years of age) have non-controlled arterial hypertension at a
             level of greater than or equal to the 90th percentile blood pressure (either systolic
             or diastolic) for their age and height or the adult participant has non-controlled
             arterial hypertension (systolic blood pressure [SBP] >160 millimeter per mercury
             (mmHg) and/or diastolic blood pressure [DBP] >100 mmHg).