Pharmacokinetics (PK) and Safety of Subgam®VF in Primary Immunodeficiency Diseases (SCIG03)

Inclusion criteria:

1. Aged between 2 and 75 years.
2. Diagnosed with primary immunodeficiency disease e.g. common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinaemia, hyper-IgM syndrome.

3. Currently receiving a licensed IGIV at a dose that has not changed by ± 50% of the mean dose for at least three months before study entry (Visit 1) and

   1. Dose is between 300 and 800 mg/kg/infusion.
   2. The infusion interval is between 21 and 28 days inclusive for IGIV.
   3. Has maintained a trough level of ≥ 5 g/L (500 mg/dL) for the last three months before Visit 1.
4. Female subjects who are (or become) sexually active must practice contraception by using a method of proven reliability for the duration of the study.
5. Females of child-bearing potential must have a negative result on an human chorionic gonadotropin (HCG)-based pregnancy test.
6. Willing to comply with all aspects of the protocol for the duration of the study.
7. Signed an informed consent form. In the case of subjects under the legal age the parent/guardian will sign an informed consent form and where appropriate the subject will sign an assent form.

Exclusion Criteria:

1. Is currently using subcutaneous IgG (SCIG).
2. Has a history of any severe anaphylactic reaction to blood or any blood-derived product.
3. Has selective IgA deficiency, history of reaction to products containing IgA, or has a history of antibodies to immunoglobulin A (IgA).
4. Has impaired cellular or innate immunity (i.e. only subjects with impaired humoral immunity to be included)
5. Has evidence of an active infection at the time of enrolment.
6. Has previously completed or withdrawn from this study.
7. Is currently receiving, or has received, any investigational agent within the prior three months.
8. Is pregnant (confirmed by a positive result on an HCG-based pregnancy test) or is nursing.

9. Is positive for any of the following at screening:

   • Serological test for Human Immunodeficiency Virus (HIV) 1&2, hepatitis C virus (HCV), or Hepatitis B Surface Antigen (HBsAg)
   • Nucleic acid Amplification Test [Polymerase Chain Reaction - PCR] (NAT) for HCV
   • NAT for HIV

10. Has levels at screening greater than 2.5 times the upper limit of normal as defined at the central laboratory of any of the following:

    • Alanine transaminase (ALT)
    • Aspartate transaminase (AST)
11. Has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or blood urea nitrogen (BUN) greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; or has a history of acute renal failure.
12. Is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
13. Has a history of deep vein thrombosis (DVT), or thrombotic complications of IGIV therapy.
14. 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, proteinuria) that the investigator feels may interfere with the conduct of the study.
15. Has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (ANC < 1000 x 109/L).

16. Is receiving the following medication:

    • Steroids (long-term daily, > 0.15 mg of prednisone equivalent/kg/day). Requirement for short or intermittent courses would not exclude a subject.
    • Immunosuppressive drugs
    • Immunomodulatory drugs
17. Has non-controlled arterial hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg).
18. Has anemia (hemoglobin < 10 g/dL) at screening.
19. Has severe dermatitis that would preclude sites for safe product administration.