About this trial
This is a phase III, non-randomized clinical trial (VIP Study) designed to assess the safety and efficacy of V-IMMUNE®, a 5% human normal immunoglobulin preparation, in approximately 50 patients with primary immunodeficiency (PID). Participants, all aged ≥2 years and already receiving IVIG therapy, will be switched to V-IMMUNE® at a dose of 600 mg/kg every three weeks via intravenous infusion. The study will use historical data as a control and extend over 12 months, with scheduled visits at each infusion (an estimated 17 infusions per participant).
Objectives and Outcomes Primary Efficacy Endpoint: Rate of serious bacterial infections over 12 months. Primary Safety Endpoint: Proportion of infusions with one or more temporally associated adverse events (AEs).
Secondary Endpoints: Additional safety outcomes (e.g., average number of AEs within 72 hours per infusion), efficacy measures (non-serious bacterial infections, time to resolution, antibiotic use, hospitalizations), and quality of life (SF-36) at 6 and 12 months. A pharmacokinetic (PK) sub-study will be conducted in 20 participants aged ≥16 years to evaluate total IgG levels, half-life, AUC, Cmax, and other PK parameters.
Study Design and Intervention V-IMMUNE® is given at an initial infusion rate of 0.01 mL/kg/min for 30 minutes, increasing stepwise up to 0.06 mL/kg/min if well tolerated. Pre-medication, including rapid IV saline, diphenhydramine, and hydrocortisone, will be administered for the first three months to reduce the risk of infusion-related AEs. Patients at elevated thromboembolic risk will receive the lowest feasible infusion rate.
Sample Size and Analysis Fifty patients total will be enrolled to ensure adequate power to demonstrate a severe infection rate below one event per person-year (with a one-sided 1% significance level). Safety endpoints will be met if the upper bound of the 95% confidence interval for the proportion of temporally associated infusion-related AEs remains below 40%, assuming a true rate under 20%. An interim analysis is planned at six months or upon reaching 50% enrollment.
20 patients at total including adults and \<16 years old, 6 children from 2 to 12 years old and 6 children from 12 to 16 years old.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients aged 2 years or older;
Agammaglobulinemia due to absence of B cells
Hypogammaglobulinemia with reduced antibody function - variable common immunodeficiency complex
Quantitative and functional deficiencies of immunoglobulin G
Disqualifiers
Acute infection under treatment within 2 weeks prior to screening
Pregnancy
History of hypersensitivity reaction to blood or blood products
Previous anaphylactic reaction to IgG
Trial design
Single group
Treatments tested in this trial
Intravenous immunoglobulin (IVIG)
Biological/VaccineThe investigational product is V-IMMUNE®, a 5% human normal immunoglobulin I.P. (5 g/100 mL) manufactured from qualified human plasma for intravenous use. Each vial contains human immunoglobulin at 50 g/L, maltose at 100 g/L, and water for injection. The 5% Human Immunoglobulin Solution for Intravenous Administration (I.P.) is a sterile and pyrogen-free preparation of human normal immunoglobulin in a single-dose form for intravenous administration. Each 10 mL, 50 mL, or 100 mL vial contains 0.5 g, 2.5 g, or 5 g of human normal immunoglobulin, respectively, and is produced from qualified human plasma using membrane filtration and a combination of chromatographic steps and viral inactivation procedures. The IgA content does not exceed 2 mg/mL. This manufacturing process uses plasma collected from donors who undergo screening according to guidelines set by regulatory authorities. In case of thromboembolic risk: use the lowest feasible dose
Treatment groups
Trial outcomes
Primary outcomes
Efficacy primary outcome
The primary efficacy endpoint is the rate of serious bacterial infections per person-year. These serious bacterial infection are: bacteremia/sepsis, bacterial meningitis, osteomielitis/septic arthritis, bacterial pneumonia, visceral abscess Definition of each serious bacterial infection are stated accordinly in the protocol.
Safety outcome
Proportion of infusions with one or more temporally associated adverse events (AEs)
Secondary outcomes
Severe and non-severe bacterial infections
Relationship of severe and non-severe bacterial infections to: The product dose Which infusion they occurred after (e.g., 1st, 2nd, 3rd, etc.) The nadir of total IgG levels Antibody levels against pneumococcal capsular polysaccharide and Haemophilus influenzae
Number of patients with 0, 1, 2, etc., severe infections
Proportion of patients with 0, 1, 2, etc., severe infections
Number of adverse events by body systems
Number of adverse events by cardiovascular, gastrointestinal, neurological, renal, hepatic, motor, and respiratory systems
Time to first infection
Time in days to first infection
Other outcomes
Cmax
Maximum plasma concentration achieved, based on experimental data, obtained directly from the plasma concentration versus time curve.
ASC0-t
Area under the plasma concentration versus time curve, from time 0 to the time of the last concentration observed above the lower limit of quantification (calculated using the trapezoidal method)
Tmax
Time at which Cmax occurs
Kel
Elimination rate constant, estimated from the slope of the regression line calculated by the least squares method using the natural logarithm of concentration versus time for the last values (at least three) above the lower limit of quantification
Sponsors and contacts
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On Pharma Importadora, Exportadora e Distribuidora de Medicamentos LTDA.
Lead sponsor
Hospital do Coracao
Collaborator