Study to Evaluate Safety and Pharmacokinetics of BIVIGAM® in Primary Immune Deficiency Subjects Aged 2 to 16

• Bivigam (Biological)

Primary outcomes

• Temporally Associated Adverse Events [During each infusion (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)]: Incidence of adverse events (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)
• Number of Temporally Associated Adverse Events [Up to 72 hours of completion of an infusion]: Mean number of temporally associated per infusion
• Serious Adverse Events [Up to approximately 7 months]: Incidence of serious adverse events
• Related Serious Adverse Events [Up to approximately 7 months]: Incidence of related serious adverse events
• Treatment Emergent Adverse Events [Up to approximately 7 months]: Incidence of treatment emergent adverse events
• Related Treatment Emergent Averse Events [Within 72 hours of infusion]: Incidence of adverse events that first appear, or that worsen relative to the pre-treatment state, which occur during and within 72 hours of treatment administration
• Non-treatment Emergent Adverse Events [Up to approximately 7 months]: Incidence of adverse events which do not have a causal relationship with study treatment
• Temporally Associated Infusion Adverse Events [Up to approximately 7 months]: Incidence of adverse events which have a causal relationship with infusion treatment
• Adverse Reactions [Up to approximately 7 months]: Number and incidence of adverse reactions plus suspected adverse reactions combined
• Related Adverse Reactions [Up to approximately 7 months]: Incidence of adverse infusion related reactions
• Infusion Site Reactions [Up to approximately 7 months]: Incidence reactions occuring at the infusion site
• Vital Signs [Before and after each administration of study drug through study completion, up to approximately 7 months]: Change in vital signs
• Temporally Associated Adverse Events Following Infusions [Up to 72 hours after each infusion through study completion, up tp approximately 7 months]: Incidence of adverse events

Secondary outcomes

• Total IgG Trough [At each visit through study completion, up tp approximately 7 months]: Levels taken before any infusion
• IgG subclasses [Prior to first and last infusion, up tp approximately 7 months]: Levels of subclasses 1- 4 before infusion
• Total IgG Post [At each infusion through study completion, up tp approximately 7 months]: End of infusion level of Total IgG
• Cmax [At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months]: Pharmacokinetic measure at 5th or 7th infusion
• Tmax [At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months]: Pharmacokinetic measure at 5th or 7th infusion
• AUC(0-ʈ) [At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months]: Pharmacokinetic measure at 5th or 7th infusion
• AUC(0-∞) [At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after infusion]: Pharmacokinetic measure at 5th or 7th infusion
• Terminal phase elimination half-life (ʈ½) [At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months]: Pharmacokinetic measure at 5th or 7th infusion
• Antibodies [At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months]: Levels of specific antibodies (antipneumococcal capsular polysaccharide, antihaemophilus influenza B
• Infections [Up to approximately 7 months]: Number of infections of any kind, serious and non-serious
• First Serious Bacterial Infection [Up to approximately 7 months]: Time to first Serious Bacterial Infections in days
• Serious Bacterial Infections [Up to approximately 7 months]: Incidence of Serious Bacterial Infections
• Other Infections [Up to approximately 7 months]: Incidence of infections other than Serious Bacterial Infections
• Resolution of Infections [Up to approximately 7 months]: Time to resolution of Infections in days
• Fever [Up to approximately 7 months]: Episodes of Fever
• Missed Days [Up to approximately 7 months]: Number of days missed of school or work due to infections and treatment
• Hospitalizations [Up to approximately 7 months]: Number of hospitalizations due to infections
• Terminal phase elimination rate (λZ) [At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months]: Pharmacokinetic measure at 5th or 7th infusion

Sex: All, ages: 2 Years to 16 Years

Inclusion Criteria:

* Written informed consent/Assent
* Male or female between 2 and 16 years, inclusive, at time of Signing Informed Consent/Assent
* Have a confirmed and documented clinical diagnosis of Primary Immune Deficiency Disorder, including hypogammaglobulinemia or agammaglobulinemia.
* Have received IGIV therapy which was maintained at a steady dose (± 25% of the mean dose) for at least 3 months prior to study entry, and have maintained a trough IgG level at least 500mg/dL prior to receiving BIVIGAM®.
* Subjects and/or parents/legal guardians must be able to understand and adhere to the study visit schedule and all other protocol requirements.

Exclusion Criteria:

* Known intolerance to immunoglobulins or comparable substances (e.g. vaccination reaction).
* Known intolerance to proteins of human origin or known allergic reactions to components of the study product(s).
* Any previous randomization/participation in this clinical study must be discussed with and approved by the medical director (or designee).
* Inability or lacking motivation to participate in the study.
* Medical condition, laboratory finding, or physical exam finding (specify, e.g., vital signs outside of specific range that precludes participation. Per lab results at the Screening visit through Baseline.
* Confirmed Screening visit laboratory results ˃2.5 X ULN as defined for pediatric populations for any of the following: ALT (alanine aminotransferase/SGPT), AST (aspartate aminotransferase/SGOT), LDH (lactate dehydrogenase), BUN (blood urea nitrogen), Serum creatinine
* Has selective IgA deficiency or demonstrated antibodies to IgA.
* History of thrombotic complications of IGIV therapy or history of (deep vein thrombosis)DVT.
* Current use of daily corticosteroids (>10 mg of prednisone equivalent/day),immunosuppressants or immunomodulators are not allowed unless approved in advance by the medical monitor. Intermittent use of corticosteroids during the study is allowed if medically necessary.
* Positive diagnosis of hepatitis B or hepatitis C.
* Positive human immunodeficiency virus (HIV) test.
* Subject has had a serious bacterial infection (SBI) within the last 3 months.
* Subject has an active infection and is receiving antibiotic therapy for the treatment of this infection at the time of Screening. Note: if the subject is deemed a Screen Failure due to a nonserious active infection requiring antibiotic therapy, the subject may be rescreened 3 or 4 weeks (depending on drug administration schedule) after the initial screening.
* Subject has a history of thrombotic events (including deep vein thrombosis, myocardial infarction, cerebrovascular accident and pulmonary embolism) within 6 months before 1st IGIV dose or has preexisting risk factors for thrombotic events.
* Acquired medical condition known to cause secondary immune deficiency such as chronic lymphacitic leukemia, lymphoma or multiple lymphoma.
* Subjects with protein-losing enteropathies, hypoalbuminaemia.
* Females taking oral contraceptives.
* Pregnancy or unreliable contraceptive measures or lactation period (females of childbearing potential (female capable of becoming pregnant) only. Males capable of reproduction must agree to a double barrier method of contraception during their study participation.

• Results publication: Dumas T, Mehr S, Avila R, Doman A, Kestenberg K, Melamed I. Pharmacokinetic Model Based Sensitivity Analysis to Lower Recruitment Burden for Young Children Requiring Intravenous Immunoglobulin G Replacement. CPT Pharmacometrics Syst Pharmacol. 2026 Jun;15(6):e70275. doi: 10.1002/psp4.70275. PMID 42218742