Safety, Tolerability, Efficacy, and Pharmacokinetic Study of ProMetic BioTherapeutics Immune Globulin Intravenous (Human) 10%

This is a pivotal Phase 3, open-label, single-arm, multicenter study to assess the
tolerability, safety, efficacy, and PK of the IMP in adults and children with PIDD. A total
of approximately 75 subjects aged 2-80 years will be enrolled in the study. Subjects who
switch from an investigational immune globulin or subcutaneous immune globulin (IGSC) are
required to receive a stable dose of commercial product (CP), which is a licensed
commercially available immune globulin intravenous (IGIV) product for at least 3 cycles
before they can be given the IMP. This study schema will result in the CP Treatment Period
and IMP Treatment Period. All subjects will be treated on an outpatient basis with the IMP
for approximately 1 year, with the dose and schedule based on their previous IGIV treatment
regimen (21-day or 28-day dosing interval). A subset of subjects will participate in a PK
sub-study.

The primary objective of the study is to examine the rate of clinically documented serious
bacterial infections (SBIs) in subjects treated with the IMP to achieve a rate of less than
one SBI per year.

Inclusion Criteria:

1. Subject is male or female between the ages of 2 and 80 years at Screening.

2. Female subjects of childbearing potential must agree to employ adequate birth control
measures, as determined by their IRB/IEC, for the duration of the study.

3. The subject must have one of the following three diagnoses (isolated PIDD of other
types will be excluded):

- Common variable immunodeficiency

- X-linked agammaglobulinemia

- Hyper-IgM syndrome and documented low IgG levels (<4.5 mg/mL [450 mg/dL]).

4. Subjects must have been treated with a stable dose of immune globulin administered
intravenously (IGIV) or subcutaneously (IGSC) and has documented trough or steady
state IgG levels of ≥ 5 mg/mL.

Exclusion Criteria:

1. Subject has secondary immunodeficiency or has been diagnosed with dysgammaglobulinemia
or isolated IgG subclass deficiency; has known hypoalbuminemia (<3 gm/dL),
protein-losing enteropathy, or nephrotic syndrome.

2. Subject has ever had a history of severe anaphylactic or anaphylactoid reaction to
immunoglobulins or other blood products.

3. Subject has a known history of immunoglobulin A (IgA) deficiency and known anti-IgA
antibodies, thrombotic event, such as deep vein thrombosis, myocardial infarction,
cerebrovascular accident, pulmonary embolism, at any time.

4. Subject has received blood products except IGIV, IGSC, or albumin within the previous
12 months or has participated in another study (except for IGIV, IGSC studies) within
the previous 4 weeks.

5. Subject has had cancer in the past 5 years, except for basal cell or squamous cell
cancers of the skin.

6. Subject has had a documented active infection within 7 days prior to Screening, or
subject is on continuous prophylactic antibiotics.

7. Subject is positive for human immunodeficiency virus (HIV)-1 or HIV-2, a positive
hepatitis C virus (HCV) or hepatitis B virus (HBV).

8. Subject has levels of alanine aminotransferase (ALT) or aspartate aminotransferase
(AST) >2.5 times the upper limit of normal (ULN).

9. Subject has serum creatinine >1.5 times the ULN or a severe chronic condition such as
renal failure with proteinuria.

10. Subject has anemia with a hemoglobin level ≤8 g/dL.

11. Subject has severe neutropenia with neutrophil count ≤1000 per mmᴧ3 or has lymphopenia
with <500 per/ mmᴧ3.

12. Subject is taking prednisone at a dose ≥0.15 mg/kg/day and receiving other
immunosuppressive drugs or chemotherapy.

13. Subject has known atrial fibrillation requiring anticoagulant therapy; congestive
heart failure (New York Heart Association Class III/IV); cardiomyopathy; or cardiac
arrhythmia associated with thromboembolic events, unstable or advanced ischemic heart
disease, or hyperviscosity.

14. Subject has known decreased Protein C and/or Protein S levels.

15. Subject is positive for antibodies to β2GPI and/or β2GPI DI at Screening.

16. Female subject who is pregnant, breast-feeding, or planning a pregnancy during the
course of the study.

17. A history of epilepsy or multiple episodes of migraine (defined as at least one
episode within 6 months of enrolment) not completely controlled by medication, or any
condition that is likely to interfere with evaluation of the IMP or satisfactory
conduct of the study in the Investigator's opinion.