BACKGROUND: The painful episodes of sickle cell disease (SCD) involve vaso-occlusion and impaired oxygen delivery. HBOC-201, a hemoglobin-based oxygen carrier, has been shown to support oxygen delivery in animal studies and to be safe and well tolerated in normal human volunteers. Therefore, we speculated that it might have a therapeutic role in SCD. METHODS:Eighteen adults with SCD who were asymptomatic at the time of study were enrolled in a Phase I/II single-blind, placebo-controlled, dose-escalation study of HBOC-201. The primary purpose was to assess 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 HBOC-201 infusions were well tolerated by the study subjects and no evidence of toxicity was noted. In addition, there was a significant difference in heart rate response to the identical aerobic exercise workload when the study subjects who received HBOC-201 were compared to the subjects who received placebo (p = 0.0061). CONCLUSIONS:HBOC-201 was safely 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 workload 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 notion that HBOC-201 could have efficacy as a treatment for the vasoocclusive episodes of SCD.
RCT Entities:
BACKGROUND: The painful episodes of sickle cell disease (SCD) involve vaso-occlusion and impaired oxygen delivery. HBOC-201, a hemoglobin-based oxygen carrier, has been shown to support oxygen delivery in animal studies and to be safe and well tolerated in normal human volunteers. Therefore, we speculated that it might have a therapeutic role in SCD. METHODS: Eighteen adults with SCD who were asymptomatic at the time of study were enrolled in a Phase I/II single-blind, placebo-controlled, dose-escalation study of HBOC-201. The primary purpose was to assess 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 HBOC-201 infusions were well tolerated by the study subjects and no evidence of toxicity was noted. In addition, there was a significant difference in heart rate response to the identical aerobic exercise workload when the study subjects who received HBOC-201 were compared to the subjects who received placebo (p = 0.0061). CONCLUSIONS: HBOC-201 was safely 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 workload 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 notion that HBOC-201 could have efficacy as a treatment for the vasoocclusive episodes of SCD.