Efficacy and Safety and Pharmacokinetics of Boya IVIG

Study Overview
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Brief Summary
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To evaluate the safety, efficacy and pharmacokinetic properties of Boya's IVIG preparation in participants with PID aged less than 60 years and more than 6 years.

Detailed Description
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This is a phase 3, open-label, prospective, single-group, multicenter study to evaluate the efficacy of IVIG in keeping the average number of serious bacterial infections to less than one per year. The safety and pharmacokinetics (PK) of the investigational product will also be assessed. Fifty male or female participants aged up to 60 years will be selected, with at least 20 participants aged between 06 and 17 years. During the study, at least 20 adult participants will be invited to make up the subgroups evaluating the pharmacokinetic parameters. The main benefit of IVIG is to help the immune system respond to a wide range of infections, which are often correlated with high morbidity and mortality rates in individuals with PID, particularly in cases of CVID and XLA. In addition, a reduction in the use of medication and hospitalizations is expected, promoting an improvement in the quality of life of these patients. IVIG therapy is generally safe, although unwanted effects are reported in a proportion ranging from 1% to 81% of patients or infusions, with an average incidence of 30% to 40% among patients and 5% to 15% among infusions. These effects can manifest themselves in varying degrees of intensity, ranging from mild to severe. They can occur immediately, during or shortly after the infusion, as well as late, appearing hours or even days after the procedure. Most adverse events are mild and immediate, occurring in the first few infusions, related to the infusion rate and quickly reversible. Headache, fever, general malaise, flu-like symptoms, nausea, chills, fatigue, myalgia, low back pain, tachycardia, changes in blood pressure and erythroderma are the most common events. Serious reactions occur in less than 1% of applications and usually with the use of higher doses, indicated in autoimmune and inflammatory diseases. Special care is needed in patients with comorbidities such as heart disease, nephropathy, liver disease, coagulation disorders (thrombophilia) and diabetes mellitus. In these patients, certain characteristics of IVIG should be assessed, such as the presence of sugars, osmolality, sodium, among others.

Official Title
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Efficacy, Safety and Pharmacokinetics of Boya Intravenous Immunoglobulin (IVIG) in Participants With Primary Immunodeficiency

Conditions
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Primary Immunodeficiency Disease

Intervention / Treatment
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* Biological: Boya IVIG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signature of written informed consent. Men or women. Age ≤ 60 years. Diagnosis of PID disease (PID) with a reduction in antibody production due to: Common variable immunodeficiency (CVID) as defined ESID/PAGID, OR X-linked agammaglobulinemia (XLA) as defined by ESID/PAGID. Receiving intravenous immunoglobulin replacement therapy at 21- or 28-day intervals at 300 to 600 mg/kg/month for a minimum of 2 months prior to study entry. Absence of episodes of serious bacterial infections with prior use of IV immunoglobulin for at least 3 months prior to screening. Negative pregnancy test (in female participants of childbearing potential); readiness to use reliable contraceptive methods throughout the study period. Patients who have participated in a clinical study with another investigational IVIG may be included if they have a potential benefit in accordance with CNS Res. 251/1997. Participants undergoing treatment with any subcutaneous or intramuscular immunoglobulin may be included by switching to IVIG therapy at the discretion of the investigator, considering the possible benefit to the participant. Exclusion Criteria: Known intolerance or hypersensitivity to immunoglobulins or components of the test article; Any contraindications to the use of immunoglobulins; Secondary immunodeficiency or conditions potentially causing secondary immunodeficiency such as chronic lymphoid leukemia, lymphoma, multiple myeloma, protein-losing enteropathies or nephropathies, and hypoalbuminemia; Clinically relevant changes in the safety exams are defined as: Blood count Hb < 10.5 g/dL Leukocytes < 3,000 / mm3 or >10,000 cells / mm3 Absolute neutrophil count < 1,000 cells/mm3; Coagulation TP and aPTT > 2.5 x ULN Biochemistry glycated hemoglobin > 6.5% total bilirubin and fractions, alkaline phosphatase, ALT, AST, GGT > 2.5 x ULN creatinine above 3mg/dl or creatinine clearance < 30mL/min Urine I. Leukocyturia > 10,000 cells/mL Any cancer either active or resolved within the last 12 months before screening; Receiving any blood products (except intravenous immunoglobulins) during the last 3 months before screening; Any febrile illness within 14 days before enrollment; Note: The patient may be rescreened after recovery. History of thrombotic events (including myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis) within 6 months before enrollment; Previous use of live attenuated virus vaccines; Selective deficiency of immunoglobulin A (IgA) or known antibodies to IgA; Known drug or alcohol abuse; The need to use other investigational drugs, systemic immunosuppressants, and any other immunoglobulins; Pregnancy or lactation; Inability to comply with the protocol activities; PIDs other than CVID or X-linked agammaglobulinemia Patients infected with HIV, HBV or HCV Patients with AIDS, cystic fibrosis, or active hepatitis B or C. Any other condition that, in the Investigator's opinion may increase the risk of participation in this study.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients with primary immunodeficiency will switch to Boya IVIG and optimize the posology in a run-in period of 2 to 6 administrations. In the one-year test period, the patients will receive the test IVIG at 21- or 28-day intervals and be followed. IgG trough levels will be collected from all participants, at all visits. The remaining pharmacokinetic parameters will be measured between visits 4 and 5 in 20 adult participants, collecting additional blood samples.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boya IVIG<br>Patients with primary immunodeficiency will switch to Boya IVIG and optimize the posology in a run-in period of 2 to 6 administrations. In the one-year test period, the patients will receive the test IVIG at 21- or 28-day intervals and be followed. The minimum IgG concentration will be measured in all participants at all visits. The other pharmacokinetic parameters will be measured between visits 4 and 5 in 20 adult participants by taking additional blood samples. An independent Safety Data Monitoring Committee (SDMC) will periodically monitor adverse events. | Biological: Boya IVIG<br>* The initial dose and other dose changes will be determined by the investigator on a case-by-case basis aiming to prevent infection and minimum serum IgG levels of 5 g/L. The total number of doses administered will depend on the treatment regimen and run-in period: Between 16 and 20 intravenous injections for participants receiving infusions every 28 days, or; Between 21 and 25 intravenous injections for participants receiving infusions every 21 days<br>* Other names: BOYA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Objective (average of acute serious bacterial infections) | The incidence of serious bacterial infections (septicemia, meningitis, visceral abscess, osteomyelitis, and pneumonia) within the 1-year follow-up is less than 1.0 per patient/year in the average of the population. | Between Visit 0 and Final Visit (through study completion, an average of 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the rate of non-serious infections within one year | The incidence of all acute infections except the serious acute bacterial infections within the 1-year follow-up (simple descriptive statistics). | Average incidence of non-serious infections per patient between Visit 0 and Final Visit (through study completion, an average of 1 year), as documented as treatment emergent adverse events (TEAEs). | 
| Length of infections | Assessment of the duration of treatment for infections per year | Average number of days for treating infections per patient between visit 0 and final visit (through study completion, an average of 1 year), as documented as treatment emergent adverse events (TEAEs) | 
| Missing time from school/work | Assessment of time lost at school/work due to infections per month | Average number of days off from school/work per patient/month, as documented in the patient's diary (through study completion, an average of 1 year) | 
| Hospitalization episodes | Assessment of hospitalization episodes and length | Number of days hospitalized per month overall and due to infection, as documented as treatment emergent adverse events - TEAEs (through study completion, an average of 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PID, BOYA, IVIG