Gammagard Liquid and rHuPH20 in PID
Condition: Primary Immunodeficiency Diseases (PID)
MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes
Intervention: Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV); Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)
Intervention description: Comprises subjects previously participating in Study 160601, who now only complete Study Epoch 2 (subcutaneous [SC] infusions) as bioavailability/exposure for intravenous (IV) treatment was already obtained in Study 160601.
Study Epoch 2: Dose (calculated) of rHuPH20 followed by dose (calculated) of IGIV, 10% by SC infusion. Treatment intervals and doses are to be increased as defined, until treatment interval is the same as the pre-study treatment interval for IV treatment (ramp-up).; Comprises all other subjects.
Study Epoch 1: IV infusion of IGIV, 10% (same dose and frequency as pre-study) to determine pharmacokinetics.
Study Epoch 2: Dose (calculated) of rHuPH20 followed by dose (calculated) of IGIV, 10% by SC infusion. Treatment intervals and doses are to be increased as defined, until treatment interval is the same as the pre-study treatment interval for IV treatment (ramp-up).
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: Parallel Assignment
Masking: None (Open Label)
Enrollment: 89.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to develop a subcutaneous treatment option for participants with
      Primary Immunodeficiency Diseases (PID) that allows an administration of Immune Globulin
      Intravenous (Human), 10% at the same frequency as IV administration.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is 2 years or older at the time of screening

          -  Written informed consent obtained from either the participant or the participant's
             legally acceptable representative prior to any study-related procedures and study
             product administration

          -  Participant has been diagnosed with a PID disorder requiring antibody replacement as
             defined by WHO criteria

          -  Participant has completed or is about to complete Baxter Clinical Study Protocol No.
             160601 or has been receiving a regular IGIV-treatment at mean intervals of 21 ± 3 days
             or 28 ± 3 days, or SC at mean intervals of 5 to 16 days, over a period of at least 3
             months prior to enrollment at a minimum dose of 300 mg/kg BW/4 weeks

          -  Participant has a serum trough level of IgG > 4.5 g/L at the last documented
             determination

          -  If female of childbearing potential, participant presents with a negative urine
             pregnancy test and agrees to employ adequate birth control measures for the duration
             of the study

          -  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 enrollment or 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

          -  Participant has levels of alanine aminotransferase (ALT) or aspartate amino
             transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory

          -  Participant has persistent severe neutropenia (defined as an absolute neutrophil count
             [ANC] <= 500/mm3)

          -  Participant has creatinine clearance (CLcr) values, calculated according to the
             formula below, which are < 60% of normal for age and gender for males: CLcr = [(140 -
             Age(years)) * (body weight (kg))] / [72 * (serum creatinine (mg/dL))] for females:
             CLcr = [(140 - Age(years)) * (body weight(kg)) * 0.85] / [72 * (serum creatinine
             (mg/dL))]

          -  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) within the last 12 months prior to enrollment; participants treated with
             immunosuppressive chemotherapeutic agents during this period are excluded

          -  Participant has a history of thrombotic episodes (including deep vein thrombosis,
             myocardial infarction, cerebrovascular accident, pulmonary embolism) within the last
             12 months

          -  Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome)

          -  Participant has anemia that would preclude phlebotomy for laboratory studies

          -  Participant has received any blood or blood product other than an IGIV, SC
             immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6
             months prior to enrollment

          -  Participant has an ongoing history of hypersensitivity or persistent reactions
             (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV,
             SC immunoglobulin, and/or ISG infusions

          -  Participant has immunoglobulin A (IgA) deficiency and known anti IgA antibodies

          -  Participant is on preventative (prophylactic) antibiotics and cannot stop antibiotics
             at the time of enrollment

          -  Participant has active infection who started on antibiotic therapy for the treatment
             of infection within 7 days prior to screening

          -  Participant has a bleeding disorder or is on anti-coagulation therapy that results in
             a platelet count less than 20,000/μL or International Normalized Ration (INR) > 2X
             control, or who, in the opinion of the investigator would be at significant risk of
             increased bleeding or bruising as a result of SC therapy

          -  Participant has total protein > 9 g/dL and participants with myeloma,
             macroglobulinemia (IgM) and paraproteinemia

          -  Participant has a known allergy to hyaluronidase

          -  If female, participant is pregnant or lactating at the time of study enrollment

          -  Participant has participated in another clinical study involving an investigational
             product (IP) or device within 30 days prior to study enrollment or is scheduled to
             participate in another clinical study involving an IP or device during the course of
             this study; exception: Baxter Study No. 160601

          -  Severe dermatitis that would preclude adequate sites for safe product administration