Development of an Anti-P-selectin Antibody for the Treatment of Sickle Cell Disea

开发用于治疗镰状细胞病的抗 P-选择素抗体

• 批准号: 8529596
• 负责人: SCOTT A ROLLINS
• 金额: $ 103.76万
• 依托单位: SELEXYS PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529596
• 关键词: Address; Affect; African American; Antibodies; Award; Biological Assay; Cell Adhesion; Cities; Clinical; Clinical Management; Clinical Protocols; Clinical Research; Clinical Trials; Contracts; Development; Doctor of Medicine; Dose; Double-Blind Method; Drug Evaluation; Enrollment; Evaluation Research; Event; Funding; Goals; Grant; Health Care Costs; Hematological Disease; Hematology; Individual; Inflammatory; Inherited; Intravenous infusion procedures; Lead; Macaca fascicularis; Manufacturer Name; Marketing; Mediating; Medical; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Oklahoma; Orphan Drugs; P-Selectin; Pain; Patient Recruitments; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Placebo Control; Play; Prevention; Process; Production; Randomized; Rare Diseases; Regulatory Pathway; Reporting; Role; Safety; Sickle Cell; Sickle Cell Anemia; Small Business Innovation Research Grant; Therapeutic; TimeLine; Work; arm; base; clinical efficacy; commercialization; design; effective therapy; efficacy trial; experience; humanized antibody; humanized monoclonal antibodies; mortality; novel; patient population; phase 1 study; phase 2 study; pre-clinical; preclinical study; prevent; programs; rat Piga protein; sickle cell crisis; volunteer

DESCRIPTION (provided by applicant): Selexys Pharmaceuticals is developing a humanized monoclonal antibody drug called SelG1 directed against P-selectin for the treatment of vasoocclusive crisis in patients with sickle cell disease. The ultimate goal of this Phase IIB proposal is to further advance SelG1 into Phase II/III safety and efficacy trials to support of regulatory filings for FDA approval and commercialization. Previous work funded in part by an NHLBI SBIR Fast Track award R44HL093893, and Selexys financing, resulted in the completion of studies to determine the pharmacology/toxicology of SelG1 in cynomolgus monkey, filing the SelG1 IND with the FDA and the completion of a Phase I safety and PK/PD normal volunteer study. The final audited Phase I study report will be submitted to the IND in Q1 2012. The aims of this proposal are directed to the conduct and analysis of a Phase II clinical efficacy and safet study to evaluate SelG1 as a therapeutic treatment for sickle cell patients. Sickle cell disease (SCD) affects over 90,000 individuals in the US and remains a debilitating condition with major unmet medical need leading to high morbidity and mortality. Selexys is developing SelG1 as a once monthly IV infusion for the prevention or reduction of vasoocclusive crisis and associated morbidities in sickle cell patients. The company has engaged in planning with key opinion leaders (KOLs) in the SCD field to develop a clinical protocol for SelG1 to be conducted in a Phase II safety and efficacy trial in approximately 120 SCD patients, powered to >88% for the validated primary endpoint of sickle cell crisis reduction. The planned study would be a 12- month double-blinded, randomized, placebo-controlled 3-arm study with two SelG1 dosing arms. The manufacturing plan is set to commence in Q1 2012 with GMP production of SelG1 at the 500-1000L scale at Cytovance Biologics in Oklahoma City. Patient recruitment and conduct of the study is projected to commence in Q2-Q3 of 2012 with an overall study duration of 18-24 months. The funds requested in this PhIIB renewal application are for support of conduct and management of the clinical program, bioanalytical assays, and analysis of the clinical trial results. It is anticipated that successful completion of the Phase II study will lead to a pivotal Phase III safety and efficacy trial with the goal of registration, FDA approval and launch of SelG1 for the treatment of vasoocclusive crisis in sickle cell patients.

描述（由申请人提供）：SELEXYS Pharmaceuticals正在开发一种人源化的单克隆抗体药物，称为针对P-选择蛋白的SELG1，用于治疗镰状细胞疾病患者的血管含量鉴定性危机。该阶段IIB提案的最终目标是将SELG1进一步发展为II/III期安全性和有效性试验，以支持监管申请以进行FDA批准和商业化。 Previous work funded in part by an NHLBI SBIR Fast Track award R44HL093893, and Selexys financing, resulted in the completion of studies to determine the pharmacology/toxicology of SelG1 in cynomolgus monkey, filing the SelG1 IND with the FDA and the completion of a Phase I safety and PK/PD normal volunteer study.最终审计的I期研究报告将在2012年第一季度提交IND。该提案的目的是针对II期临床疗效和SAFET研究的行为和分析，以评估SELG1作为镰状细胞患者的治疗方法。镰状细胞疾病（SCD）在美国影响90,000多人，并且仍然是令人衰弱的状况，其医疗需求很大，导致高发病和死亡率。 Selexys正在将SELG1作为曾经每月的IV输注，以预防或减少镰状细胞患者的血管占性危机和相关的病因。该公司已与SCD领域的主要意见领导者（KOLS）进行了计划，以在大约120名SCD患者的II期安全和效力试验中开发临床方案，以降低镰状细胞危机的验证主要终点。计划的研究将是一个12个月的双盲，随机，安慰剂对照的3臂研究，并有两个SELG1剂量臂。制造计划定于2012年第一季度开始，在俄克拉荷马城的Cytovance Biologics的500-1000L量表中GMP生产SELG1。该研究的患者招募和行为预计将于2012年第2 Q3 Q3开始，总体研究持续时间为18-24个月。在此PHIIB更新应用中要求的资金是为了支持临床计划的行为和管理，生物分析测定以及对临床试验结果的分析。预计，成功完成II期研究将导致III期关键性安全和功效试验，其目的是注册，FDA批准和SELG1的启动，以治疗镰状细胞患者的血管含量危机。