V-IMMUNE® for Primary Immunodeficiency: A Phase III Clinical Trial (VIP Study)
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.
• Patients aged 2 years or older;
• Primary immunoglobulin G deficiency, already receiving another intravenous immunoglobulin (IVIG). Primary IgG deficiency may be secondary (non-exhaustive list) to one of the following diagnoses:
• Agammaglobulinemia due to absence of B cells
• Hypogammaglobulinemia with reduced antibody function - variable common immunodeficiency complex
• Quantitative and functional deficiencies of immunoglobulin G
• Normal immunoglobulin with reduced capacity for antibody production after immunization (e.g., Wiskott-Aldrich syndrome, IgG subclass deficiency, antipolysaccharide antibody deficiency against Haemophilus or pneumococcus)
• Severe combined immunodeficiencies: DiGeorge syndrome presenting with immunoglobulin G deficiency
• Isotype-switching defects: hyperimmunoglobulinemia M syndromes
• Two trough IgG measurements ≥500 mg/dL within the past 90 days.
• Participants with through IgG measurements ≥700 mg/dL within the last 30 days before the first visit