6R-BH4 IN SUBJECTS WITH SICKLE CELL DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：本研究旨在评价每日一次口服给药的安全性和生物活性。 4次递增剂量的6R-BH4用于镰状细胞病患者。 受试者：多达40名受试者将在美国5-6个地点进行筛选和登记。 程序：筛选后，符合条件的研究参与者将在为期16周的剂量递增阶段接受每日一次的口服6R-BH4剂量，受试者体内的剂量水平每4周增加一次。在剂量升级之前，调查员将使用预定义的参数评估每个受试者S在上一剂量水平的安全概况。如果受试者不符合升级到下一个剂量水平的标准，或者剂量降低，他们将获得16周期间的最高耐受剂量。6R-BH4的整体安全状况将在赞助商和调查人员之间的定期安全审查会议上进行评估。在为期16周的剂量递增阶段之后，参与者可以在长达2年的延长阶段继续服用耐受性最高的研究药物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Purpose: This study is designed to assess the safety and biologic activity of once daily oral administration of 4 escalating doses of 6R-BH4 to subjects with sickle cell disease. Subjects: Up to 40 subjects will be screened and enrolled at 5-6 sites in the United States. Procedures: After screening, eligible study participants will receive oral, once-daily doses of 6R-BH4 during a 16-week dose-escalation phase, with dose levels increasing within subjects every 4 weeks. Prior to dose escalation, the Investigator will evaluate each subject s safety profile during the previous dose level, using predefined parameters. If a subject does not meet the criteria for escalation to the next dose level or is de-escalated in dose, they will receive their highest tolerated dose for the duration of the 16-week period. The overall safety profile of 6R-BH4 will be evaluated during periodic safety review meetings between the Sponsor and Investigators. Following the 16-week dose escalation phase,participants may continue on the highest tolerated study drug in an extension phase lasting up to 2 years.