Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
Condition: Primary Immune Deficiency Disorders; Common Variable Immunodeficiency; X-linked Agammaglobulinaemia; Hyper-IgM Syndrome
MeSH terms: Agammaglobulinemia; Hyper-IgM Immunodeficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency
Intervention: Gammaplex (5%); Gammaplex 10
Intervention MeSH terms: gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 2 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      The primary objective is to demonstrate the bioequivalence of Gammaplex® 10 intravenous
      immunoglobulin (IGIV) and Gammaplex® 5% IGIV with respect to area under the curve within a
      28-day dosing interval (AUC0-28) in a cohort of adult subjects.

      The secondary objectives are to demonstrate the bioequivalence of Gammaplex® 10 IGIV and
      Gammaplex® 5% IGIV with respect to area under the curve within a 21-day dosing interval
      (AUC0-21) in adult subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV and
      Gammaplex 5% IGIV including Immunoglobulin G (IgG) trough levels and to investigate the
      safety and tolerability of Gammaplex 10 IGIV and Gammaplex 5% IGIV in adults subjects; to
      assess the pharmacokinetics of Gammaplex 10 IGIV including IgG trough levels and to
      investigate the safety and tolerability of Gammaplex 10 IGIV in pediatric subjects.
    

Eligibility criteria:

        Inclusion criteria:

          1. Adult cohort: The subject is aged 16 to 55 years inclusive, is of either sex, and
             belongs to any ethnic group.

             Pediatric cohort: The subject is aged 2 to 15 years inclusive, is of either sex,
             weighs at least 10 kg, and belongs to any ethnic group.

          2. The subject has primary immunodeficiency disease, e.g. common variable
             immunodeficiency, X linked and autosomal forms of agammaglobulinemia, hyper IgM
             (Immunoglobulin M) syndrome. Isolated deficiency of a single IgG subclass or of
             specific antibodies without hypogammaglobulinemia per se, does not qualify for
             inclusion.

          3. The subject is currently receiving a licensed IGIV (or investigational stage III, IIIb
             IGIV) at a dose that has not changed by ± 50% of the mean dose for at least three
             months before study entry and is between 300 and 800 mg/kg/infusion. The infusion
             interval must be either every 21 or every 28 days.

          4. The subject must have a trough level ≥ 6 g/L (600 mg/dL). At least one documented
             trough level must be available from the three months before Screening.

          5. The subject must have documentation from the last three consecutive routine IGIV
             infusions for the following, before the first infusion in this study: dose of IGIV,
             treatment intervals, and trade name (or identity) of the IGIV treatment.

          6. Female subjects of childbearing potential must have a negative result on an HCG (human
             chorionic gonadotropin) based pregnancy test at Screening.

          7. Females who are or become sexually active must practice contraception using a method
             of proven reliability for the study duration.

          8. The subject is willing to comply with all aspects of the protocol for the duration of
             the study.

          9. The subject has signed an informed consent form and assent form (if applicable).

        Exclusion criteria:

          1. The subject has a history of any severe anaphylactic reaction to blood or any blood
             derived product.

          2. The subject has selective IgA deficiency, history of reaction to products containing
             IgA (Immunoglobulin A), or has a history of antibodies to IgA.

          3. The subject has cellular or innate impaired immunity (i.e. only subjects with humoral
             impaired immunity may be included).

          4. The subject has evidence of an active infection at the time of enrolment.

          5. The subject has previously completed or withdrawn from this study.

          6. The subject is currently receiving, or has received, any investigational agent other
             than an IGIV within the prior three months.

          7. The subject is pregnant or is nursing.

          8. The subject has positive results for any of the following at Screening:

               -  Serological test for HIV 1 and 2, HCV, or HBsAg

               -  NAT (Nucleic acid amplification technique)for HCV

               -  NAT for HIV

          9. The subject has levels > 2.5 times the upper limit of normal, as defined at the
             central laboratory, of any of the following at Screening:

               -  Alanine amino transaminase

               -  Aspartate amino transaminase

         10. The subject has severe renal impairment (defined as serum creatinine greater than two
             times the upper limit of normal or blood urea nitrogen greater than 2.5 times the
             upper limit of normal for the range of the laboratory doing the analysis); the subject
             is on dialysis; the subject has a history of acute renal failure.

         11. The subject is known to abuse alcohol, opiates, psychotropic agents, or other
             chemicals or drugs, or has done so within the past 12 months.

         12. The subject has a history of deep vein thrombosis or thrombotic complications of IGIV
             therapy.

         13. The subject suffers from any acute or chronic* medical condition (e.g. renal disease
             or predisposing conditions for renal disease, coronary artery disease, or protein
             losing state) that the Investigator feels may interfere with the conduct of the study.

         14. The subject has an acquired immunodeficiency condition such as chronic* lymphocytic
             leukemia, lymphoma, multiple myeloma, or chronic or recurrent neutropenia (absolute
             neutrophil count < 1 × 109/L).

         15. The subject is receiving the following medication:

               -  Steroids (long term daily, ≥ 0.15 mg of prednisone equivalent/kg/day).
                  Requirement for short or intermittent courses of steroids would not exclude a
                  subject.

               -  Immunosuppressive drugs

               -  Immunomodulatory drugs

         16. The subject has uncontrolled arterial hypertension (systolic blood pressure > 160 mm
             Hg and/or diastolic blood pressure > 100 mm Hg).

         17. The subject has anemia (hemoglobin < 10 g/dL) at Screening.

         18. The subject is known to be intolerant to any component of Gammaplex, such as sorbitol
             (i.e. hereditary intolerance to fructose) or glycine.

               -  Chronic conditions would be as per the Investigator's opinion however for this
                  study the guidance is that the condition has been present for at least 6 months.