Safety, PK/PD, and Efficacy of NOX-H94 in Dialysis Patients With ESA-hyporesponsive Anemia: A Randomized, Double Blind, Placebo Controlled Parallel Group Study With a Single Blind Cross-over Group

Dialysis patients regularly suffer from anemia which may be caused by various contributing factors, alone or in combination, including blood loss, low erythropoietin and iron sequestration. In most patients, the anemia is responsive to treatment with erythropoietin or other erythropoiesis stimulating agents (ESA) alone or in combination with intravenous (i.v.) iron. In about 10% of patients however, the anaemia does not respond appropriately to this standard treatment and high to very high doses of ESA and i.v. iron are used to maintain acceptable hemoglobin concentrations. In these patients, hepcidin was identified as a causative factor leading to anemia of chronic disease with functional iron deficiency and ESA-hyporesponsiveness.
The Spiegelmer lexaptepid pegol (NOX-H94) offers a hepcidin-specific approach to the treatment of anemia of chronic disease. The safety and the activity of lexaptepid pegol are supported by data from healthy subjects and patients with multiple myeloma or lymphoma. The present study in dialysis patients with functional iron deficiency and ESA-hyporesponsiveness is conducted to demonstrate the safety of lexaptepid pegol in this population, to investigate its pharmacokinetic (PK) and pharmacodynamic (PD) profiles and its efficacy in increasing haemoglobin (Hb) in dialysis patients.

开始日期2014-05-01

申办/合作机构

TME Pharma NV

NCT01691040 / Completed临床2期

Phase IIa Study to Characterize the Effects of the Spiegelmer® NOX H94 on Anemia of Chronic Disease in Patients With Cancer

This study is conducted to determine the safety, tolerability, and efficacy of NOX-H94 in patients with anemia of chronic disease (ACD). Furthermore, this study is intended to provide data needed to correlate plasma concentrations of NOX-H94 with its efficacy and to choose the appropriate dose and dose schedule of subsequent efficacy studies.
Some chronic diseases, e.g. tumors, inflammation, renal disease, are associated with high hepcidin concentrations in the blood. These hepcidin concentrations cause a reduction in iron concentrations in the blood and subsequently impair formation of red blood cells. Treatment with NOX-H94 is expected to inhibit this patho-mechanism by binding and inactivating hepcidin.

开始日期2012-09-01

申办/合作机构

TME Pharma NV

DRKS00003478 / Completed临床1期

Randomized double blind placebo controlled PK/PD study on the effects of a single intravenous dose of NOX H94 on serum iron during experimental human endotoxemia

开始日期2012-01-30

申办/合作机构

NOXXON Pharma AG

100 项与 Lexaptepid pegol 相关的临床结果

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100 项与 Lexaptepid pegol 相关的转化医学

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100 项与 Lexaptepid pegol 相关的专利（医药）

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项与 Lexaptepid pegol 相关的文献（医药）

2016-05-01·British journal of pharmacology2区 · 医学

Safety, pharmacokinetics and pharmacodynamics of the anti‐hepcidin Spiegelmer lexaptepid pegol in healthy subjects

2区 · 医学

Article

作者: Riecke, K ; Schwoebel, F ; Warrington, S ; Boyce, M ; Vauléon, S ; Summo, L ; Zöllner, S ; Cortezi, B ; Swinkels, D W

Background and Purpose:

Anaemia of chronic disease is characterized by impaired erythropoiesis due to functional iron deficiency, often caused by excessive hepcidin. Lexaptepid pegol, a pegylated structured l‐oligoribonucleotide, binds and inactivates hepcidin.

Experimental Approach:

We conducted a placebo‐controlled study on the safety, pharmacokinetics and pharmacodynamics of lexaptepid after single and repeated i.v. and s.c. administration to 64 healthy subjects at doses from 0.3 to 4.8 mg·kg−1.

Key Results:

After treatment with lexaptepid, serum iron concentration and transferrin increased dose‐dependently. Iron increased from approximately 20 μmol·L−1 at baseline by 67% at 8 h after i.v. infusion of 1.2 mg·kg−1 lexaptepid. The pharmacokinetics showed dose‐proportional increases in peak plasma concentrations and moderately over‐proportional increases in systemic exposure. Lexaptepid had no effect on hepcidin production or anti‐drug antibodies. Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses ≥2.4 mg·kg−1 and with local injection site reactions after s.c. but not after i.v. administration.

Conclusions and Implications:

Lexaptepid pegol inhibited hepcidin and dose‐dependently raised serum iron and transferrin saturation. The compound is being further developed to treat anaemia of chronic disease.

2015-01-01·Drug discovery today2区 · 医学

Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer® therapeutics

2区 · 医学

Review

作者: Vater, Axel ; Klussmann, Sven

Spiegelmers are synthetic target-binding oligonucleotides built from non-natural l-nucleotides. Like aptamers, Spiegelmers fold into distinct shapes that bind the targets with high affinity and selectivity. Furthermore, the mirror-image configuration confers plasma stability and immunological passivity. Various Spiegelmers against pharmacologically attractive targets were shown to be efficacious in animal models. Three Spiegelmer candidates: emapticap pegol (NOX-E36; anti-CCL2), olaptesed pegol (NOX-A12; anti-CXCL12) and lexaptepid pegol (NOX-H94; anti-hepcidin), underwent regulatory safety studies, demonstrated good safety profiles in healthy volunteers and were taken into Phase IIa studies in patients. Proof-of-concept for emapticap pegol has recently been demonstrated in diabetic nephropathy patients. Furthermore, promising interim Phase IIa data of olaptesed pegol and lexapteptid pegol also suggest efficacy in the respective patient populations.

100 项与 Lexaptepid pegol 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12578

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
终末期肾脏病	临床2期	德国	TME Pharma NV	2014-05-01
终末期肾脏病	临床2期	意大利	TME Pharma NV	2014-05-01
终末期肾脏病	临床2期	英国	TME Pharma NV	2014-05-01
贫血	临床2期	奥地利	TME Pharma NV	2012-09-01
贫血	临床2期	保加利亚	TME Pharma NV	2012-09-01
贫血	临床2期	罗马尼亚	TME Pharma NV	2012-09-01
肿瘤	临床2期	奥地利	TME Pharma NV	2012-09-01
肿瘤	临床2期	保加利亚	TME Pharma NV	2012-09-01
肿瘤	临床2期	罗马尼亚	TME Pharma NV	2012-09-01
内毒素血症	临床1期	荷兰	TME Pharma NV	2012-01-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01372137 (Pubmed \| Br J Pharmacol) 人工标引	临床1期	贫血	64	lexaptepid pegol	繭淵鏇網廠鬱衊艱獵選(簾廠鑰遞齋齋壓築鹹製) = Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses ≥2.4 mg·kg(-1) and with local injection site reactions after s.c. but not after i.v. administration. 鏇艱蓋鏇壓網繭範衊窪 (獵選鏇艱淵顧選齋鏇鏇 )	积极	2016-05-01
NCT01372137 (Pubmed \| Br J Pharmacol) 人工标引	临床1期	贫血	64	Placebo		积极	2016-05-01
NCT01522794 (Pubmed \| Circulation)	临床1期	炎症	24	Lexaptepid	廠蓋簾齋鹹膚遞構壓壓(糧遞淵積淵夢顧艱襯鹹) = 簾蓋夢艱鬱簾艱夢繭衊蓋糧鏇蓋夢築選鏇鬱選 (齋壓齋鬱餘構網壓鏇繭 )	-	2014-10-23
NCT01691040 (AACR2014)	临床2期	慢性淋巴细胞白血病 \| 多发性骨髓瘤 \| 伴随慢性肾病的贫血	12	Lexaptepid pegol (LP)	顧鏇鹽淵鑰獵夢築鑰窪(鹽遞鑰廠齋餘獵遞衊蓋) = 構範憲憲簾遞憲夢窪夢選觸襯範餘淵窪廠觸餘 (製顧獵餘鹹醖餘鬱餘顧 ) 更多	积极	2014-10-01