Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10)

Inclusion Criteria:

1. Written informed consent/assent obtained from the patient and his/her parent(s) orlegally acceptable representative indicating that they understand the purpose of andprocedures required for the study and are willing to participate in it.

2. Confirmed clinical diagnosis of a PID as defined by 2017 International Union ofImmunological Societies (IUIS) Phenotypic Classification for PrimaryImmunodeficiencies (Bousfiha A, 2018 - and subsequent revisions) and The EuropeanSociety for Immunodeficiencies (ESID) Registry Working Definitions for the ClinicalDiagnosis of Inborn Errors of Immunity (Seidel MG et al., 2019 - and subsequentrevisions) and requiring treatment with IVIg. Documented agammaglobulinemia (definedas the total absence of one or more classes of antibodies) or hypogammaglobulinemia (defined as low levels of one or more classes [i.e., at least 2 standard deviationsunder the mean level per age]).

(NOTE: IVIg treatment is generally requested in the absence of IgG independentlyfrom whether other antibodies are absent).

3. Male or female, age from 2 up to < 16 years, at the time of screening.

4. Received 200 to 800 mg/kg of a commercially available IVIg therapy in the range of 21- or 28-day intervals (±3 or ±4 days, respectively) for at least 3 infusions priorto screening.

(NOTE: Other IVIgs will be prohibited after ICF signature and until study end, week 51/52).

5. At least 2 documented IgG trough levels while receiving an IVIg, of ≥ 6 g/L obtainedat 2 infusions within 12 months (1 must be within 6 months) prior to ICF signature.

6. Patient and his/her parent(s)/legal guardian(s) are willing to comply with allrequirements of the protocol.

7. Females of child-bearing potential with a negative pregnancy test (serum or urine)and who agree to employ adequate birth control measures during the study, such as:

8. sexual abstinence, to be evaluated in relation to the preferred and usuallifestyle of the subject;

9. male or female condom with or without spermicide;

10. cap, diaphragm or sponge with spermicide;

11. progestogen-only oral hormonal contraception, if already used in the past onmedical prescription. Adequate birth control measures should be maintained throughout the study underparental control.

12. Authorization to access personal health information.

13. Patients previously participating in a clinical trial with another experimental IVIgmay be enrolled if they have received stable commercially available IVIg therapy forat least 3 infusions (21 or 28 days) prior to screening.

14. Patients currently on treatment with any subcutaneous immunoglobulin (SCIG) can beenrolled if they are switched to stable commercially available IVIg therapy for atleast 3 infusions (21 or 28 days) prior to screening.

15. Males or females with a body weight greater than or equal to 15 kg (≥ 15 kg).

Exclusion Criteria:

1. Newly diagnosed PID and naïve to IgG replacement therapy.

2. Dysgammaglobulinemia (defined as a deficiency in one or more classes of antibodies,but not severe enough to require substitutive therapy) or isolated IgG subclassdeficiency, or profound primary T cell deficiency (defined as the absence or severereduction of T lymphocytes [CD3+ < 300 cell/mm3] and an absent or particularly lowproliferative response [10% of the lower normal range] to phytohaemagglutinin P [PHA]).

3. History of severe or serious reactions or hypersensitivity to IVIg or otherinjectable forms of IgG.

4. History of thrombotic events including deep vein thrombosis, cerebrovascularaccident, pulmonary embolism, transient ischemic attacks, or myocardial infarction,as defined by at least 1 event in patient's lifetime.

5. IgA deficiency with documented antibodies to IgA.

6. Received blood products that have not undergone viral inactivation measures within 12 months prior to ICF signature.

7. Significant protein losing enteropathy, nephrotic syndrome, or lymphangiectasia.

8. An acute infection as documented by culture or diagnostic imaging and/or a bodytemperature ≥38.5 °C (≥101.3 °F) within 7 days prior to screening.

9. Acquired immunodeficiency syndrome (AIDS) and/or hepatitis B/C active disease at ICFsignature.

10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times ofthe upper limit of normal for the laboratory designated for the study.

11. Using an implanted venous access device.

12. Moderate or severe anemia, defined according to patient's age as shown in thefollowing table (World Health Organization, 2011) or persistent severe neutropenia (≤ 500 neutrophils per mm3) or persistent lymphopenia of less than 500 cells permicroliter.

13. A severe chronic condition such as renal failure [defined as abnormalities in kidneystructure or function that are present for more than 3 months and have healthimplications. The disease is classified on the basis of cause and category ofglomerular filtration rate (GFR) (G1 to G5) and albuminuria (A1 to A3) (KIDIGO, 2017). See the following table], congestive heart failure (New York HeartAssociation III/IV), cardiomyopathy, cardiac arrhythmia associated withthromboembolic events (e.g., atrial fibrillation), unstable or advanced ischemicheart disease, hyperviscosity, or any other condition that the Investigator believesis likely to interfere with evaluation of the study drug or with satisfactoryconduct of the trial.

14. History of a malignant disease other than properly treated carcinoma in situ of thecervix or basal cell or squamous cell carcinoma of the skin within 24 months priorto ICF signature.

15. History of pharmacoresistant epilepsy or multiple episodes of migraine (defined asat least 1 episode within 6 months of ICF signature) not controlled by medication.

16. Patient must not be receiving the following medication from at least 30 days priorto ICF signature:

17. Steroids, inhaled, oral or parenteral, at a daily dosage of ≥ 0.15 mg/kg/day ofprednisone or equivalent).

18. Other immunosuppressive drugs (including monoclonal antibodies) orchemotherapy.

19. Females who are pregnant, breast feeding or planning a pregnancy during the courseof the study. Women who become pregnant during the study will be withdrawn from thestudy.

20. Participated in another clinical study within 30 days prior to ICF signature.

21. Active drug or alcohol abuse or history of drug or alcohol abuse within the 6 monthsbefore screening.

22. Direct relative of an employee of the CRO, the study site, or Kedrion.

23. Previously treated under this protocol.

24. Unable to provide informed consent.

25. Patients with any condition which, in the opinion of the Investigator, mightinterfere with the evaluation of the study objectives or the patient's participationin this trial.

26. Patients with Hypersensitivity to the active substance or to any of the excipients.