[Translation] A randomized, open-label, two-period, two-sequence crossover phase I clinical trial to evaluate the bioequivalence and food effect of KL130008 capsules in healthy subjects

主要目的：1）比较KL130008胶囊（新/旧处方）在健康受试者中给药后的药代动力学特征。 2）探索食物对KL130008胶囊（新处方）在健康受试者中药代动力学的影响。次要目的：评估KL130008胶囊（新/旧处方）在健康受试者中的安全性和耐受性。

[Translation]

Primary objectives: 1) Compare the pharmacokinetic characteristics of KL130008 capsules (new/old prescription) after administration in healthy subjects. 2) Explore the effect of food on the pharmacokinetics of KL130008 capsules (new prescription) in healthy subjects. Secondary objectives: Evaluate the safety and tolerability of KL130008 capsules (new/old prescription) in healthy subjects.

Start Date04 May 2023

Sponsor / Collaborator

Sichuan Kelun Botai Biomedicine Co., Ltd.

ChiCTR2300070146 / SuspendedPhase 1IIT

Evaluation of the randomized, open, two-week, cross-sequence bioequivalence and food effects of KL130008 capsule in healthy subjects

Start Date05 Apr 2023

Sponsor / Collaborator-

NCT05496426 / Not yet recruitingPhase 2

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Trial Evaluating the Safety and Efficacy of KL130008 Capsule in Patients With Severe Alopecia Areata

The purpose of this study is to assess KL130008 is safe and effective in adults with severe alopecia areata

Start Date31 Oct 2022

Sponsor / Collaborator

Sichuan Kelun Pharmacy Institute Co., Ltd.

100 Clinical Results associated with KL130008

100 Translational Medicine associated with KL130008

100 Patents (Medical) associated with KL130008

Literatures (Medical) associated with KL130008

01 Sep 2022·European Journal of Pharmaceutical Sciences

Randomized, double-blinded, placebo-controlled phase I study of the pharmacokinetics, pharmacodynamics, and safety of KL130008, a novel oral JAK inhibitor, in healthy subjects

Article

Author: Wang, Ying ; Li, Na ; Gong, Yimou ; Niu, Yuanyuan ; Lu, Huifang ; Men, Yuchun ; Cheng, Yezhe ; He, Miao ; Wang, Yongsheng ; Chen, Jing ; Shu, Shiqing ; Feng, Ping ; Zhu, Xiaohong ; Du, Shuangqing ; Gu, Liling ; He, Qiang ; Xu, Ying ; Fang, Fang

BACKGROUND AND OBJECTIVESKL130008 is a novel selective inhibitor of Janus kinase (JAK) 1/2 that may have therapeutic benefit against rheumatoid arthritis (RA) and other autoimmune diseases. Here, we developed a first-in-human trial of KL130008 to evaluate its pharmacokinetics (PK), pharmacodynamics (PD), and safety in healthy subjects.METHODSRandomized, double-blinded, placebo-controlled phase I study was designed. Healthy Chinese subjects received KL130008 in single-ascending doses (1-20 mg) or multiple-ascending doses (2-6 mg) once daily for seven days, and data on PK, PD, and safety data including QT interval were evaluated.RESULTSA total of 79 subjects were enrolled, of whom 77 completed the study. After oral administration following at least a 10-h fast, KL130008 was rapidly absorbed and reached a maximum concentration (C_max) in 0.6-1.5 h. KL130008 exposure was approximately linear and dose-proportional. The drug showed exponential elimination with t_1/2 = 14-18 h, and 8-20% of KL130008 was excreted in the urine. Dose-dependent inhibition of the phosphorylated signal transduction and transcriptional activator 3 (p-STAT3) was observed in subjects who received single KL130008 doses of 4-20 mg, while multiple dosing of KL130008 at 2, 4, or 6 mg once daily for seven consecutive days sustainably inhibited p-STAT3. The rates of treatment-emergent adverse events were 88.7% with KL130008 and 81.3% with placebo. All such events were grade 1 or 2 and disappeared or resolved by the end of the study. The most frequent such events were a decrease in neutrophil percentage, which occurred in 30.6% of subjects on KL130008; a decrease in neutrophil count, which occurred in 29.0% of subjects on KL130008; and an increase in lymphocyte percentage, which occurred in 25.8% of subjects on KL130008. None of these three events occurred while subjects were on placebo.CONCLUSIONOur results support that KL130008 is a safe and well-tolerated oral JAK1/2 inhibitor. The present study may help optimize the KL130008 dosing regimen for a phase II study.CLINICAL TRIAL REGISTRATION NUMBERChiCTR1800018743 (chictr.org); registered on October 7, 2018.

PLOS ONEQ3 · CROSS-FIELD

Reversal of MicroRNA Dysregulation in an Animal Model of Pulmonary Hypertension

Q3 · CROSS-FIELD

ArticleOA

Author: Johnson, Larry G ; Gubrij, Igor B ; Pang, Li ; Pangle, Amanda K

BACKGROUNDAnimals models have played an important role in enhancing our understanding of the pathogenesis of pulmonary arterial hypertension (PAH). Dysregulation of the profile of microRNAs (miRNAs) has been demonstrated in human tissues from PAH patients and in animal models. In this study, we measured miRNA levels in the monocrotaline (MCT) rat model of PAH and examined whether blocking a specific dysregulated miRNA not previously reported in this model, attenuated PAH. We also evaluated changes in miRNA expression in lung specimens from MCT PAH rats overexpressing human prostacyclin synthase, which has been shown to attenuate MCT PAH.METHODSExpression levels of a panel of miRNAs were measured in MCT-PAH rats as compared to naïve (saline) control rats. Subsequently, MCT PAH rats were injected with a specific inhibitor (antagomiR) for miR-223 (A223) or a nonspecific control oligonucleotide (A-control) 4 days after MCT administration, then weekly. Three weeks later, RV systolic pressure and RV mass were measured. Total RNA, isolated from the lungs, microdissected pulmonary arteries, and right ventricle, was reverse transcribed and real-time quantitative PCR was performed. MiRNA levels were also measured in RNA isolated from paraffin sections of MCT-PAH rats overexpressing prostacyclin synthase.RESULTSMiRs 17, 21, and 223 were consistently upregulated, whereas miRs 126, 145, 150, 204, 424, and 503 were downregulated in MCT PAH as compared to vehicle control. A223 significantly reduced levels of miR-223 in PA and lungs of MCT PAH rats as compared to levels measured in A-control or control MCT PAH rats, but A223 did not attenuate MCT PAH. Right ventricular mass and right ventricular systolic pressure in rats treated with A223 were not different from values in A-control or MCT PAH rats. In contrast, analysis of total RNA from lung specimens of MCT PAH rats overexpressing human prostacyclin synthase (hPGIS) demonstrated reversal of MCT-induced upregulation of miRs 17, 21, and 223 and an increase in levels of miR-424 and miR-503. Reduction in bone morphogenetic receptor 2 (BMPR2) messenger (m)RNA expression was not altered by A223, whereas human prostacyclin synthase overexpression restored BMPR2 mRNA to levels in MCT PAH to levels measured in naive controls.CONCLUSIONSInhibition of miR-223 did not attenuate MCT PAH, whereas human prostacyclin synthase overexpression restored miRNA levels in MCT PAH to levels detected in naïve rats. These data may establish a paradigm linking attenuation of PAH to restoration of BMPR2 signaling.

100 Deals associated with KL130008

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Alopecia Areata	Phase 2	CN	Sichuan Kelun Pharmacy Institute Co., Ltd.	31 Oct 2022
Rheumatoid Arthritis	Phase 2	CN	Sichuan Kelun Botai Biomedicine Co., Ltd.	12 Oct 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ChiCTR1800018743 (Pubmed) Manual	Phase 1	-	79	KL 130008	(ectjpfycmw) = sjxvrvxusc dskqxnbncr (lnccsrhqjg ) View more	Positive	09 Jul 2022
				Placebo	(ectjpfycmw) = hienspknpv dskqxnbncr (lnccsrhqjg )

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