Safety and Pharmacokinetics of IGSC 20% in Subjects With Primary Immunodeficiency
Condition: Primary Immunodeficiency
MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes
Intervention: IGIV-C 10%; IGSC 20%
Intervention description: IGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen; IGSC 20% weekly infusions with dose calculated based on previous IgG regimen
Intervention MeSH terms: Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin; Immunoglobulin G
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 2 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This study was designed to determine a dose of weekly subcutaneously administered Immune
      Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols) (IGSC 20%)
      that produces steady-state AUC of total IgG that was non-inferior to that of the regularly
      administered intravenous dose of Immune Globulin Injection (Human), 10%
      Caprylate/Chromatography Purified (Grifols) (IGIV-C 10%) in primary immunodeficiency
      subjects. This study was also designed to determine steady state trough total IgG levels
      after IGSC 20% infusion and after IGIV-C 10% infusion for comparison and to assess the safety
      and tolerability of IGSC 20%.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pre-existing diagnosis of primary immunodeficiency with features of
             hypogammaglobulinemia requiring IgG replacement therapy

          -  No serious bacterial infection within the last 3 months prior to or during Screening

          -  Currently on IgG replacement therapy (via IV or SC infusion) for ≥3 consecutive
             months. Subjects receiving IGIV must be receiving a dosage of 300 to 800 mg/kg per
             infusion

          -  Documented (at least once within previous 3 months) IgG trough level of ≥500 mg/dL on
             current IgG replacement therapy regimen

        Exclusion Criteria:

          -  Known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction
             to blood or any blood-derived product

          -  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

          -  Isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or
             transient hypogammaglobulinemia of infancy

          -  Nephrotic syndrome, and/or a history of acute renal failure and/or severe renal
             impairment, and/or on dialysis

          -  History (year prior to Screening or 2 episodes in lifetime ) of or current diagnosis
             of deep venous thrombosis or thromboembolism (eg, deep vein thrombosis, myocardial
             infarction, cerebrovascular accident or transient ischemic attack)

          -  Acquired medical condition known to cause secondary immune deficiency, such as chronic
             lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia
             (absolute neutrophil count less than 1000/μL [1.0 x 10^9/L]), or human
             immunodeficiency virus infection/acquired immune deficiency syndrome

          -  Known previous infection with or clinical signs and symptoms consistent with current
             hepatitis B virus or hepatitis C virus infection

          -  Non-controlled arterial hypertension (systolic blood pressure >160 mmHg and/or
             diastolic blood pressure >100 mmHg in adult subjects)

          -  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
             subject. Inhaled or topical corticosteroids are allowed.