A PHASE I II STUDY OF POLYMERIZED BOVINE HEMOGLOBIN IN ADULT PATIENTSWITH SICKLE-CELL DISEASE NOT IN CRISIS AT THE TIME OF STUDY/

Background: The painful episodes of sickle cell disease (SCD) involve vaso-occlusion and impaired oxygen delivery, HBOC-201, a hemoglobin-ba sed oxygen carrier, has been shown to support oxygen delivery in anima l studies and to be safe and well tolerated in normal human volunteers , Therefore, are speculated that it might have a therapeutic role in S CD, Methods: Eighteen adults with SCD who were asymptomatic at the tim e of study were enrolled in a Phase I/II single-blind, placebo-control led, dose-escalation study of HBOC-201, The primary purpose was to ass ess the safety of the material in this patient population, In addition , as a surrogate marker of efficacy, each subject underwent a variety of exercise tests before and after HBOC-201 was given, Results: All HB OC-201 infusions were well tolerated by the study subjects and no evid ence of toxicity was noted, In addition, there was a significant diffe rence in heart rate response to the identical aerobic exercise workloa d when the study subjects who received HBOC-201 were compared to the s ubjects who received placebo (p = 0.0061), Conclusions: HBOC-201 was s afely administered to patients with SCD who were not in crisis at the time of study, Furthermore, following infusion of the study material, subjects with SCD performed the identical aerobic exercise-induced wor kload with an increase in heart rate that was significantly less than the increase observed in the subjects who received an infusion of the saline placebo, These safety and surrogate efficacy data support the n otion that HBOC-201 could have efficacy as a treatment for the vaso-oc clusive episodes of SCD.