Safety and Tolerability of a New Intravenous Immunoglobulin (IVIg) 10% (KIg10) in Primary Immunodeficiency (PI) Adult Patients

Introduction Intravenous immunoglobulin (IVIg) therapy is commonly used in the treatment of primary immunodeficiency (PI) disorders. This open-label, prospective, single-arm, multicenter phase III study in adult PI patients (KIG10_US3_PID01; NCT01581593) investigated efficacy, safety and pharmacokinetics (PK) of a new 10% IVIg product (KIg10), given 200 to 800 mg/kg every 21 or 28 days for 48 weeks. Objective Safety and tolerability endpoints from this study are reported here and included treatment-emergent adverse events (TEAEs) from Day 1 to Week 51/52. Methods Forty-seven patients received study treatment and were analyzed for safety and efficacy. As per protocol, the 1st infusion was administered at an initial rate of 1 mg/kg/min for 30 minutes. If well tolerated, the rate was progressively increased to a maximum of 8 mg/kg/min. The rate of administration of subsequent infusions progressively increased to a maximum of 8 mg/kg/min at 15-min intervals. Results Among both dosing schedules, 22 (46.8%) subjects reported 75 TEAEs. Most frequently reported (≥5%) were headache (25.5%), infusion-related reaction (10.6%), nausea, fatigue, and positive Coombs direct test (8.5% each). The most frequently reported (≥5%) infusional adverse event (AE) (defined as occurring during or within 72 hours after an infusion) were headache (25.5%), fatigue (14.9%), infusion-related reaction (10.6%), nausea (10.6%), positive Coombs direct test (10.6%), diarrhea (6.4%), dizziness (6.4%), and sinusitis (6.4%). No hemolysis events were reported, and no laboratory findings were suggestive of hemolysis associated with positive Coombs tests. No safety signal or trend was observed. None of the reported TEAEs were serious; no significant or life-threatening TEAEs were reported. No AEs led to study discontinuation, and no subjects died during the study due to an AE. Conclusion In study KIG10_US3_PID01, KIg10 showed a favorable safety profile and was well tolerated in adult patients with PI at the dosing schedules and infusion rates used.