Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
Condition: Primary Immunodeficiency
MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes
Intervention: IgPro20
Intervention description: A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject's physician prior to study entry.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No

Summary:

      This multicenter, open-label, parallel-arm, non-randomized study is designed to evaluate
      safety and tolerability of higher infusion parameters of IgPro20 in subjects with primary
      immunodeficiency (PID). A total of 45 subjects (including at least 14 [30%] pediatric
      subjects ≤ 17 years of age and at least 9 [20%] obese subjects with body mass index [BMI] of
      ≥30 kg/m2) with confirmed PID will be evaluated in the study. The study will include three
      cohorts of 15 subjects each as follows: i) Pump-Assisted Volume Cohort (weekly infusions),
      volume per injection site of 25 mL up to 50 mL, ii) Pump Assisted Flow Rate Cohort (weekly
      infusions), flow rate per injection site of 25 mL/hour up to 100 mL/hour, iii) Manual Push
      Flow Rate Cohort (2 to 7 infusions per week), flow rate per injection site of 25 to 30
      mL/hour up to 120 mL/hour (equivalent of approximately 0.5 mL/minute up to 2 mL/minute). Each
      cohort will test 3 infusion parameter levels (4 for the pump-assisted flow rate cohort),
      repeated at least 4 times over a duration of 12 weeks (16 weeks for the flow rate cohort).
      After 4 infusion weeks at each level, qualifying subjects (responders) will switch to the
      next infusion parameter level (eg, from 25 to 50 mL/h). During the study, the weekly dose
      will remain unchanged (as prescribed by treating physician, usually within 100-200 mg/kg per
      week range); only the respective infusion parameter under evaluation will change.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female on stable dose of IgPro20 (Hizentra) therapy.

          -  Women of childbearing potential must be using and agree to continue using medically
             approved contraception (which must be discussed with the study doctor) and must have a
             negative pregnancy test at screening.

          -  Subjects with PID, eg, with a diagnosis of common variable immunodeficiency or
             X-linked agammaglobulinemia, as defined by the Pan American Group for Immune
             Deficiency and the European Society of Immune Deficiencies.

          -  With infusion parameters as specified below:

        Pump-Assisted Flow Rate Cohort subjects only

          -  Experience with pump-assisted infusions of IgPro20 at the tolerated flow rate of 25
             mL/h per injection site for at least 1 month prior to Day 1.

        Pump-Assisted Volume Cohort subjects only

          -  Total weekly IgPro20 dose of ≥ 50 mL (≥ 10 g).

          -  Experience with pump-assisted infusions of IgPro20 at tolerated volumes of 25
             mL/injection site for at least 1 month prior to Day 1.

        Manual Push Flow Rate Cohort subjects only

          -  Experience with frequent (2-7 times per week) infusions of IgPro20 at the tolerated
             flow rate of approximately 0.5 mL/min (equivalent of 25-30 mL/h) per injection site
             for at least 1 month prior to Day 1. The dose (volume) per injection site should not
             exceed 25 mL.

        Exclusion Criteria:

          -  Ongoing serious bacterial infections at the time of screening.

          -  Other significant medical conditions that could increase the risk to the subject.

          -  Females who are pregnant, breast feeding, or planning a pregnancy during the course
             study.

          -  Participation in a study with an Investigational Medicinal Product (IMP) other than
             IgPro20 within three months prior to enrollment.