CD24 Targeting for Multiple Sclerosis: a First-In-Human Phase I Study

描述（由申请人提供）：多发性硬化症（MS）是一种常见的慢性神经系统疾病，大约每1000名高加索人中就有1人患病，特别是居住在温带气候的北欧人。虽然目前还没有治愈多发性硬化症的方法，但一些药物可以延缓复发-缓解型多发性硬化症（RRMS）患者临床恶化的进展。然而，对于原发性和继发性进展性多发性硬化症（PPMS和SPMS）尚无治疗方法。十多年来，我们一直致力于研究CD24在多发性硬化症中的作用。我们在动物模型中的研究表明，CD24的主要功能是调节自身反应性T细胞到达中枢神经系统后的持久性。遗传研究表明，CD24的多态性控制着多发性硬化症的风险和/或进展。基于这些新的观察结果，我们投入了超过10年的时间来开发靶向CD24治疗多发性硬化症的疗法。我们已经完成了EAE动物模型和非人灵长类动物的制造、疗效和毒性研究。我们最近收到FDA批准我们的IND进行首次人体研究。在此，我们提出了一项随机、双盲、安慰剂对照、单次递增剂量的研究，以评估CD24Fc在健康成人中的安全性、耐受性、免疫原性和药代动力学。第一阶段的研究将由全国最受尊敬的cro之一进行，在临床药物测试方面有着良好的记录。本文提出的I期研究将为II期研究的决定提供关键的安全性信息。人体PK和免疫原性数据将对II期研究的设计有价值。

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a common chronic neurological disorder affecting approximately 1 in 1000 Caucasians, particularly persons of Northern European origin who reside in temperate climates. Although there is still no cure for MS, several drugs can delay the progression of clinical worsening of patients with relapsing-remitting MS (RRMS). However, no treatment is available for primary and secondary progressive MS (PPMS and SPMS). For more than 10 years, we have focused our research on the role of CD24 in MS. Our studies in animal models established that the primary function of CD24 is to regulate the persistence of autoreactive T cells after they have reached the CNS. The significance of this checkpoint for MS is supported by genetic studies that demonstrate that a polymorphism of CD24 controls risk and/or progression of MS. Based on these novel observations, we have devoted more than 10 years of effort to develop therapeutics that target CD24 for the treatment of MS. We have completed manufacture, efficacy, and toxicity studies in animal models of EAE and in non-human primates. We have recently received FDA approval of our IND for a first-in- human study. Here we propose a randomized, double-blind, placebo-controlled, single ascending dose study to assess the safety, tolerability, immunogenicity and pharmacokinetics of CD24Fc in healthy adult subjects. The phase I studies will be carried out by one of the most respected CROs in the nation with strong track record in clinical drug testing. The phase I studies proposed herein will provide crucial safety information for a go-no-go decision of the phase II studies. The human PK and immunogenicity data will be valuable for the design of phase II studies.