Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: Lessons learned from the midpoint analysis

•We are evaluating a single 400 mg/kg dose of IVIG (Gamunex) in an ongoing phase II clinical study in SCD patients that are hospitalized for VOC. Here we report the results of a pre-specified, age stratified midpoint biomarker and safety analysis of this study, lessons learned and future plans.•A total of 37 acute pain crises were randomized at a ratio of 1 IVIG:1 equivalent-volume normal saline control at a dosing level of 400 mg/kg IVIG. A single dose was administered.•Baseline traits were not statistically different and the 2 groups were well matched.•The Gamunex was very well tolerated with no thrombosis, immune hemolysis or worsening renal function and no statistically significant differences for additional safety outcomes reported in either cohort.•Evaluation of neutrophil activation biomarkers showed significant improvement in the IVIG cohorts 24 h after IVIG administration, whereas in the placebo arm these values continued to increase as the VOC progressed – this includes percentage and absolute aged neutrophil counts as well as mean fluorescent intensity of activated Mac-1.•There was a non-significant trend towards a benefit for the intervention group in the