A multi-center, open-label, single-arm trial has demonstrated the efficacy and safety of Immunoglobulin Subcutaneous (IGSC) 20% for the treatment of primary immunodeficiency (PI) in adults, adolescents, and children. The study, conducted across 22 centers in eight countries, evaluated the annualized rate of serious bacterial infections (SBIs) in subjects receiving weekly IGSC 20% infusions.
Study Design and Patient Population
The phase 3 study enrolled 61 subjects with PI, including 19 children (≤12 years), 10 adolescents (>12–16 years), and 32 adults. Participants had impaired antibody production, including combined immunodeficiency syndromes. Subjects received weekly IGSC 20% at the same dose as their previous IgG regimen (DAF 1:1), with a minimum dose of 100 mg/kg/week for 52 weeks. The primary endpoint was the rate of SBIs per person per year.
Efficacy Results
The study met its primary objective, demonstrating a low rate of SBIs per person per year of 0.017. The one-sided 99% upper confidence limit was 0.036 (< 1), leading to the rejection of the null hypothesis (SBI rate per person per year ≥ 1). This indicates that weekly IGSC 20% administration effectively reduces the risk of serious bacterial infections in PI patients.
Secondary Endpoints and IgG Levels
Secondary endpoints included the rate of any infection, antibiotic treatment, hospitalizations due to infection, and mean total IgG trough levels during steady state. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008–0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83–1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively.
Safety Profile
IGSC 20% demonstrated a favorable safety profile. Seven subjects experienced serious treatment-emergent adverse events (TEAEs), but none were drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate.
Clinical Implications
The findings support the use of IGSC 20% as a safe and effective IgG replacement therapy for patients with PI. Subcutaneous administration offers advantages such as convenience, ease of use, and greater independence for patients, potentially improving adherence and quality of life. The study confirms that IGSC 20% can maintain adequate IgG levels and reduce the risk of serious infections in this patient population.
