Phase IIb Clinical Study to Assess the Safety and Efficacy of CN128 Tablets in the Treatment of Iron Overload in Transfusion Dependent Thalassemia With Sever Liver Iron Overloaded Patients Aged 16 and Above

The safety and efficacy of CN128 is studied in thalassaemia with sever liver iron overloaded patients.

开始日期2022-06-02

申办/合作机构

杭州泽德医药科技有限公司

CTR20201051 / Completed临床2期

CN128片治疗16周岁及以上输血依赖型地中海贫血患者的铁过载的安全性和有效性的IIa期临床研究

（1）评价研究期间不良事件、不良反应、严重不良事件、严重不良反应等，考察其安全性；（2）评价16周岁及以上输血依赖型地中海贫血患者口服CN128片后，随时间推移血清铁蛋白的含量变化，考察其有效性；（3）评价16周岁及以上输血依赖型地中海贫血患者口服CN128片12、24周后对肝脏铁的排铁效果，考察其有效性；（4）评价16周岁及以上输血依赖型地中海贫血患者口服CN128片12、24周后对心脏铁的排铁效果，考察其有效性；（5）评价口服CN128片12、24周后，肝脏铁下降或不变的16周岁及以上输血依赖型地中海贫血患者比例，考察其有效性；（6）评价16周岁及以上输血依赖型地中海贫血患者长期口服CN128片（延长治疗随访期）的安全性和有效性。

开始日期2020-09-30

申办/合作机构

杭州泽德医药科技有限公司

100 项与 CN-128 相关的临床结果

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100 项与 CN-128 相关的转化医学

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100 项与 CN-128 相关的专利（医药）

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项与 CN-128 相关的文献（医药）

2020-11-04·ACS Chemical Neuroscience3区 · 医学

Effectiveness of the Iron Chelator CN128 in Mitigating the Formation of Dopamine Oxidation Products Associated with the Progression of Parkinson’s Disease

3区 · 医学

Article

作者: Sun, Yingying ; Zheng, Haolin ; Waite, T. David ; Hider, Robert C. ; Pham, A. Ninh

The occurrence and progression of Parkinson's disease (PD) has been associated with the observation of elevated iron concentrations in the substantia nigra pars compacta (SNpc). While the reasons for the impact of elevated iron concentrations remain unclear, one hypothesis is that the presence of labile iron induces the oxidation of dopamine (DA) to toxic quinones such as aminochrome (DAC) and reactive oxygen species (ROS). As such, one of the proposed therapeutic strategies has been the use of iron chelators such as deferiprone (DFP) (which is recognized to have limitations related to its rapid degradation in the liver) to reduce the concentration of labile iron. In this study, a detailed investigation regarding the novel iron chelator, CN128, was conducted and a kinetic model developed to elucidate the fundamental behavior of this chelator. The results in this work reveal that CN128 is effective in alleviating the toxicity induced by iron and DA to neurons when DA is present at moderate concentrations. When all the iron is chelated by CN128, the formation of DAC and the oxidation of DA can be reduced to levels identical to that in the absence of iron. The production of H₂O₂ is lower than that generated via the autoxidation of the same amount of DA. However, when severe leakage of DA occurs, the application of CN128 is insufficient to alleviate the associated toxicity. This is attibuted to the less important role of iron in the production of toxic intermediates at high concentrations of DA. CN128 is superior to DFP with regard to the reduction in formation of DAC and elevation in DA concentration. In summary, the results of this study suggest that prodromal application of the chelator CN128 could be effective in preventing the onset and slowing the early stage development of PD symptoms associated with oxidants and toxic intermediates resulting from the iron-mediated oxidation of the neurotransmitter dopamine with CN128 likely to be superior to DFP in view of its greater in vivo availability and less problematic side effects.

2020-04-23·Journal of Medicinal Chemistry1区 · 医学

CN128: A New Orally Active Hydroxypyridinone Iron Chelator

1区 · 医学

Article

作者: Liu, Zudong ; Yuan, Xin ; Yu, Yongping ; Hider, Robert C. ; Jiang, Huidi ; Lu, Zidong ; Brown, Kathryn ; Du, Houbing ; Pan, Xiuhong ; Kong, Sisi ; Zhang, Guolin ; Kong, Xiaole ; Nandi, Manasi ; Chen, Wenteng ; Li, Zhi

Deferoxamine, deferiprone, and deferasirox are used for the treatment of systemic iron overload, although they possess limitations due to lack of oral activity, lower efficacy, and side effects. These limitations led to a search for an orally active iron chelator with an improved therapeutic index. The lower efficacy of deferiprone is due to rapid glucuronidation, leading to the formation of a nonchelating metabolite. Here, we demonstrate that the influence of metabolism can be reduced by introducing a sacrificial site for glucuronidation. A log P-guided investigation of 20 hydroxpyridinones led to the identification of CN128. The Fe(III) affinity and metal selectivity of CN128 are similar to those of deferiprone, the log P value is more lipophilic, and its iron scavenging ability is superior. Overall, CN128 was demonstrated to be safe in a range of toxicity assessments and is now in clinical trials for the treatment of β-thalassemia after regular blood transfusion.

100 项与 CN-128 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
铁过剩	临床2期	中国	杭州泽德医药科技有限公司	2020-09-30
地中海贫血	临床2期	中国	杭州泽德医药科技有限公司	2020-09-30
输血依赖性地中海贫血	临床2期	中国	杭州泽德医药科技有限公司	2020-09-30
再生障碍性贫血	临床1期	中国	杭州泽德医药科技有限公司	2020-11-24
骨髓增生异常综合征	临床1期	中国	杭州泽德医药科技有限公司	2020-11-02