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

描述(申请人提供)：多发性硬化症(MS)是一种常见的慢性神经疾病，大约每1000名高加索人中就有1人受到影响，特别是居住在温带气候的北欧血统的人。虽然目前MS尚无治愈方法，但有几种药物可延缓复发缓解型MS(RRMS)患者的临床恶化。然而，对于原发性和继发性进展性多发性硬化症(PPMS和SPMS)，没有可用的治疗方法。10多年来，我们的研究主要集中在CD24在多发性硬化中的作用。我们在动物模型上的研究证实，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。这个检查点对MS的意义得到了遗传学研究的支持，这些研究表明CD24基因的多态性控制着MS的风险和/或进展。基于这些新的观察，我们投入了10多年的努力来开发针对CD24的治疗MS的疗法。我们已经完成了在EAE动物模型和非人类灵长类动物中的制造、疗效和毒性研究。我们最近获得了FDA批准我们的IND进行第一次人体研究。在这里，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在健康成人受试者中的安全性、耐受性、免疫原性和药代动力学。第一阶段的研究将由美国最受尊敬的CRO之一进行，该CRO在临床药物测试方面有着良好的记录。本文建议的第一阶段研究将为第二阶段研究的决定提供关键的安全信息。人的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.