Phase 2 Teriparatide for Tx of Idiopathic Osteoporosis in Premenopausal Women

描述（由申请人提供）： 绝经前女性的IOP定义为发生在年轻、其他方面健康、性腺功能完整且无继发性骨质丢失的女性中的骨质疏松症。 绝经前妇女的IOP是一种罕见的疾病。 在美国，根据记录的低创伤骨折或低股骨颈骨矿物质密度（BMD）的妇女，估计患病率约为113，000。 目前尚无FDA批准的用于绝经前IOP女性的治疗方法，其中许多人患有持续性多发性骨折或BMD极低。 该提案寻求对II期临床试验的支持，以研究特立帕鲁肽（人重组PTH（1-34））治疗绝经前女性IOP的疗效和安全性。 这是基于研究者以前的工作，他们定义了这种疾病的微结构异常：薄皮质，骨小梁丢失，骨小梁板减少，刚度或强度降低。 该研究将检验中心假设，即用特立帕肽（一种增加成骨细胞介导的骨形成的药物）进行合成代谢治疗，将安全地增加绝经前IOP女性的面积和体积BMD。 在这项随机化和安慰剂对照的2期临床试验中，研究者将描述特立哌酮对IOP女性的面积和体积BMD、微结构、重塑、硬度、矿化和胶原性质的影响。 研究人员将使用最先进的和新颖的方法来进行骨骼宏观和微观成像，这些方法从未应用于IOP治疗。 这些新方法将为绝经前妇女急需的IOP治疗方法提供合理的基础，并将对临床实践产生重大影响。 通过研究IOP的治疗和改善患有不明原因骨质疏松症的年轻女性的健康，该提案解决了FDA孤儿产品开发办公室OPD资助计划的关键目标，即支持用于罕见疾病或目前没有治疗方法的疾病的产品的临床开发。

DESCRIPTION (provided by applicant): IOP in premenopausal women is defined as osteoporosis that occurs in young, otherwise healthy women with intact gonadal function and no secondary cause of bone loss. IOP in premenopausal women is an uncommon disorder. The estimated prevalence in the United States, based on women with documented low trauma fractures or low femoral neck bone mineral density (BMD), is approximately 113,000. There is no FDA-approved therapy for premenopausal women with IOP, many of whom have sustained multiple fractures or have extremely low BMD. This proposal seeks support for a Phase 2 clinical trial to investigate the efficacy and safety of teriparatide, human recombinant PTH(1-34), for IOP in premenopausal women. It is based upon previous work of the investigators in which they defined microarchitectural abnormalities in this disorder: thin cortices, trabecular bone loss, fewer trabecular plates, and reduced stiffness or strength. The study will test the central hypothesis that anabolic therapy with teriparatide, a drug that increases osteoblast-mediated bone formation, will safely increase areal and volumetric BMD in premenopausal women with IOP. In this Phase 2 clinical trial, which is randomized and placebo-controlled, the investigators will characterize effects of teriparatide on areal and volumetric BMD, microarchitecture, remodeling, stiffness, mineralization and collagen properties in women with IOP. The investigators will use both state-of-the-art and novel approaches to skeletal macro- and micro-imaging that have never been applied to the therapy of IOP. These new approaches will provide a rational basis for a much needed therapeutic approach to IOP in premenopausal women and will have high impact upon clinical practice. By investigating the therapy of IOP and improving the health of young women with unexplained osteoporosis, this proposal addresses a key goal of the FDA's Office of Orphan Product Development OPD grant program, namely to support the clinical development of products for use in rare diseases or conditions where no current therapy exists.