Objectives: The INTERCEPTTM Blood System for Red Blood Cells (RBC) (Cerus Corporation, CA) uses amustaline (S-303) and glutathione (GSH) to inactivate a broad spectrum of viruses, bacteria, protozoa and T-cells. Phase 3 clinical trials were conducted in two populations: cardiovascular surgery (CVS) and transfusion dependent thalassemia (TDT) patients.  

Methods: CVS patients were randomized to receive S-303/GSH (Test) or conventional (Control) RBC during a 7-day transfusion period during and after surgery.  The primary endpoint was the mean hemoglobin (Hb) content per RBC component analysed by non-inferiority.  Secondary endpoints included: all adverse events (AE) and treatment emergent antibodies to RBC.  In the TDT study, patients underwent 6 transfusion episodes with both Test and Control RBC in a two-treatment period, crossover design. The primary efficacy endpoint analysed for non-inferiority was Hb consumption during each treatment period as a measure of the iron burden of transfusion. The primary safety endpoint was antibodies to S-303/GSH RBC.
Results: 51 CVS patients (Test 25, Control 26) were evaluable in the acute anemia study1. The mean Hb content met the criteria for equivalence (Test  53.1 g versus Control 55.8 g) based on a non- inferiority margin of 5 g.  There were no statistical differences in the overall incidence of AE rates. 81 subjects were transfused in the TDT study2. Mean Hb consumption was 0.113 ± 0.04 g/kg/day for S-303/GSH RBC and 0.111 ± 0.04 g/kg/day for Control RBC (difference 0.002 g/kg/day with a non-inferiority margin <0.017g/kg/day). No treatment-emergent S-303 RBC-specific antibodies were detected. Adverse events were balanced between Test and Control periods. 
Conclusion: S-303/GSH-RBCs were non-inferior to Control RBC in both CVS and TDT patients. The safety profile was not different from Control RBC and no antibodies were detected to S-303 RBC. 
1 V Brixner et al. Transfusion 2018; 58: 905-16
2 Y Aydinok et al Transfusion 2018; 58 Supplement S2

Phase III clinical trials with Amustaline/Glutathione (S-303/GSH) Pathogen-Inactivated RBC