A Randomized, Double-blind, Parallel, Vehicle Controlled, Repeat Dose Comparative Phase 1b Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ORTD-1 in Rheumatoid Arthritis Patients With Mild Disease Managed With DMARDs

This is a randomized, vehicle controlled, double-blind, repeat dose comparative study in patients with rheumatoid arthritis (RA) under management with DMARDs and with persistent disease activity. The goal of this study is to evaluate the safety, tolerability and pharmacokinetics of 6 weekly repeat doses of ORTD-1.

开始日期2021-03-22

申办/合作机构

Oryn Therapeutics LLC

100 项与 ORTD-1 相关的临床结果

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100 项与 ORTD-1 相关的转化医学

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100 项与 ORTD-1 相关的专利（医药）

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项与 ORTD-1 相关的文献（医药）

2001-04-01·Biochemistry3区 · 生物学

Three-Dimensional Structure of RTD-1, a Cyclic Antimicrobial Defensin from Rhesus Macaque Leukocytes^,

3区 · 生物学

Article

作者: Trabi, Manuela ; Craik, David J. ; Schirra, Horst Joachim

Most mammalian defensins are cationic peptides of 29-42 amino acids long, stabilized by three disulfide bonds. However, recently Tang et al. (1999, Science 286, 498-502) reported the isolation of a new defensin type found in the leukocytes of rhesus macaques. In contrast to all the other defensins found so far, rhesus theta defensin-1 (RTD-1) is composed of just 18 amino acids with the backbone cyclized through peptide bonds. Antibacterial activities of both the native cyclic peptide and a linear form were examined, showing that the cyclic form was 3-fold more active than the open chain analogue [Tang et al. (1999) Science 286, 498-502]. To elucidate the three-dimensional structure of RTD-1 and its open chain analogue, both peptides were synthesized using solid-phase peptide synthesis and tert-butyloxycarbonyl chemistry. The structures of both peptides in aqueous solution were determined from two-dimensional (1)H NMR data recorded at 500 and 750 MHz. Structural constraints consisting of interproton distances and dihedral angles were used as input for simulated-annealing calculations and water refinement with the program CNS. RTD-1 and its open chain analogue oRTD-1 adopt very similar structures in water. Both comprise an extended beta-hairpin structure with turns at one or both ends. The turns are well defined within themselves and seem to be flexible with respect to the extended regions of the molecules. Although the two strands of the beta-sheet are connected by three disulfide bonds, this region displays a degree of flexibility. The structural similarity of RTD-1 and its open chain analogue oRTD-1, as well as their comparable degree of flexibility, support the theory that the additional charges at the termini of the open chain analogue rather than overall differences in structure or flexibility are the cause for oRTD-1's lower antimicrobial activity. In contrast to numerous other antimicrobial peptides, RTD-1 does not display any amphiphilic character, even though surface models of RTD-1 exhibit a certain clustering of positive charges. Some amide protons of RTD-1 that should be solvent-exposed in monomeric beta-sheet structures show low-temperature coefficients, suggesting the possible presence of weak intermolecular hydrogen bonds.

PLOS ONE3区 · 综合性期刊

Significance of overall concurrent chemoradiotherapy duration on survival outcomes of stage IIIB/C non-small-cell lung carcinoma patients: Analysis of 956 patients

3区 · 综合性期刊

ArticleOA

作者: Besen, Ali Ayberk ; Selek, Ugur ; Mertsoylu, Huseyin ; Ozdemir, Yurday ; Sezer, Ahmet ; Kucuk, Ahmet ; Topkan, Erkan

BACKGROUNDTo investigate the detrimental effects of prolonged overall radiotherapy duration (ORTD) on survival outcomes of stage IIIB/C NSCLC patients treated with concurrent chemoradiotherapy (C-CRT).METHODSThe study cohort consisted of 956 patients who underwent C-CRT for stage IIIB/C NSCLC. Primary endpoint was the association between the ORTD and overall survival (OS) with locoregional progression-free survival (LRPFS) and PFS comprising the secondary endpoints. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of the cut-off that interacts with survival outcomes. Multivariate Cox model was utilized to identify the independent associates of survival outcomes.RESULTSThe ROC curve analysis exhibited significance at 49 days of ORTD cut-off that dichotomized patients into ORTD<50 versus ORTD≥50 days groups for OS [area under the curve (AUC): 82.8%; sensitivity: 81.1%; specificity: 74.8%], LRPFS (AUC: 91.9%; sensitivity: 90.6%; specificity: 76.3%), and PFS (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%), respectively. Accordingly, ORTD≥50 days group had significantly shorter median OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001); and 10-year actuarial locoregional control (P<0.001) and distant metastases-free (P<0.011) rates than the ORTD<50 days group. The ORTD retained its significant association with survival outcomes at multivariate analyses independent of the other favorable covariates (p<0.001, for OS, LRPFS, and PFS): Stage IIIB disease (versus IIIC), lymph node bulk <2 cm (versus ≥2 cm), and 2-3 chemotherapy cycles (versus 1). The higher sensitivity for LRPFS (90.6%) than PFS (72.4%) on ROC curve analysis suggested the prolonged ORTD-induced decrements in locoregional control rates as the major cause of the poor survival outcomes.CONCLUSIONSLonger ORTD beyond ≥50 days was associated with significantly poorer OS, LRPFS and PFS outcomes, where reduced locoregional control rates appeared to be the main causative.

100 项与 ORTD-1 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
新型冠状病毒感染	临床2期	美国	Oryn Therapeutics LLC	2021-04-01
COVID-19 呼吸道感染	临床2期	美国	Oryn Therapeutics LLC	2021-04-01
类风湿关节炎	临床2期	美国	Oryn Therapeutics LLC	2021-03-22