A Randomized, Double-Blind, Placebo-Controlled, Phase Ib Study to Evaluate the Safety, Tolerability, And Pharmacokinetics of Gusacitinib in Subjects With Systemic Lupus Erythematosus (SLE)

Background:
Systemic lupus erythematosus (SLE), also called lupus, is a disease that causes the body s immune system to attack healthy tissue. Lupus causes swelling and inflammation in the skin, skin, joints, kidneys, brain, blood vessels, and other organs. There is no cure for lupus. Current treatments do not help everyone and may have adverse effects. Better treatments are needed.
Objective:
To test a study drug (Gusacitinib) in people with lupus.
Eligibility:
People aged 18 years and older with lupus.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests and a test of their heart function. They will have a chest X-ray. They will have tests that use blood pressure cuffs to measure blood flow and pressure throughout the body.
Participants will have 9 clinic visits and 6 phone visits over about 7 months.
The study has 3 parts.
Part 1: Gusacitinib is a tablet taken by mouth. Participants will be divided into 3 groups. One group will receive the study drug, and a second group will get a placebo. The placebo looks like the study drug but does not contain any medicine. Both of these groups will take their tablets once a day for 12 weeks. The third group will continue to take their usual medications for lupus throughout the study.
Part 2: All participants who took the study drug or placebo in part 1 will take the study drug once a day for 12 weeks.
Part 3: All participants who took the study drug will stop taking it for 4 weeks.

Start Date22 Jan 2025

Sponsor / Collaborator-

NCT04021082

/ WithdrawnPhase 2/3

CELTIC-1 (Clinical Evaluation of T-cell NHL With Cerdulatinib): A Phase 2b, Open Label, Multidose, Multinational Study of Cerdulatinib (PRT062070) in Patients With Relapsed/Refractory Peripheral T-cell Lymphoma (PTCL)

This is an open-label, multinational study of cerdulatinib in patients with relapsed/refractory PTCL dosed with cerdulatinb, designed to (1) Evaluate tumor response, (2) Assess the safety and tolerability of cerdulatinib, (3) Evaluate duration of response (DUR), progression free survival (PFS) and overall survival(OS), (4) Determine the PK properties of cerdulatinib, (5) Evaluate the efficacy endpoints based on Lugano criteria per IRC and (6)To assess the relationship between target expression (e.g., spleen tyrosine kinase [SYK], Janus kinase [JAK]) and relevant anomalies (e.g., SYK-ITK translocation, mutations in the JAK/STAT pathway) with clinical response.

Start Date15 Nov 2019

Sponsor / Collaborator

Portola Pharmaceuticals LLC

NCT04103060

/ CompletedPhase 2

A Phase 2a, Randomized, Double-Blind, Vehicle-Controlled Study to Assess the Safety, Tolerability, and Systemic Exposure of Cerdulatinib Gel, 0.37% in Adults With Vitiligo

This is a phase 2a, randomized, double-blind, vehicle-controlled study to assess the safety, tolerability, and systemic exposure of cerdulatinib gel, 0.37% in adults with vitiligo

Start Date27 Sep 2019

Sponsor / Collaborator

Dermavant Sciences GmbH

100 Clinical Results associated with JAK1 x Syk x JAK3

100 Translational Medicine associated with JAK1 x Syk x JAK3

0 Patents (Medical) associated with JAK1 x Syk x JAK3

Literatures (Medical) associated with JAK1 x Syk x JAK3

01 Sep 2022·European Journal of Medicinal Chemistry

Dual-target Janus kinase (JAK) inhibitors: Comprehensive review on the JAK-based strategies for treating solid or hematological malignancies and immune-related diseases

Review

Author: Wang, Yezhi ; Qin, Lian ; Jia, Xiangxiang ; Shen, Pei ; Li, Zhiyu ; Feng, Xi ; Qiu, Zhixia ; Xu, Pengfei

Janus kinases (JAKs) are the non-receptor tyrosine kinases covering JAK1, JAK2, JAK3, and TYK2 which regulate signal transductions of hematopoietic cytokines and growth factors to play essential roles in cell growth, survival, and development. Dysregulated JAK activity leading to a constitutively activated signal transducers and activators of transcription (STAT) is strongly associated with immune-related diseases and cancers. Targeting JAK to interfere the signaling of JAK/STAT pathway has achieved quite success in the treatment of these diseases. However, inadequate clinical response and serious adverse events come along by the treatment of monotherapy of JAK inhibitors. With better and deeper understanding of JAK/STAT pathway in the pathogenesis of diseases, researchers start to show huge interest in combining inhibition of JAK and other oncogenic targets to realize a broader regulation on pathological processes to block disease development and progression, which has hastened extensive research of dual JAK inhibitors over the past decades. Until now, studies of dual JAK inhibitors have added BTK, SYK, FLT3, HDAC, Src, and Aurora kinases to the overall inhibitory profile and demonstrated significant advantage and superiority over single-target inhibitors. In this review, we elucidated the possible mechanism of synergic effects caused by dual JAK inhibitors and briefly describe the development of these agents.

01 Jan 2021·Journal of Molecular ModelingQ4 · CHEMISTRY

Investigation of Alpinia calcarata constituent interactions with molecular targets of rheumatoid arthritis: docking, molecular dynamics, and network approach

Q4 · CHEMISTRY

Article

Author: Ekambaram, Sanmuga Priya ; Coumar, Mohane Selvaraj ; Erusappan, Thamizharasi ; Kondapuram, Sree Karani

Rheumatoid arthritis (RA) is a systemic autoimmune disorder that commonly affects multiple joints of the body. Currently, there is no permanent cure to the disease, but it can be managed with several potent drugs that cause serious side effects on prolonged use. Traditional remedies are considered promising for the treatment of several diseases, particularly chronic conditions, because they have lower side effects compared to synthetic drugs. In folklore, the rhizome of Alpinia calcarata Roscoe (Zingiberaceae) is used as a major ingredient of herbal formulations to treat RA. Phytoconstituents reported in A. calcarata rhizomes are diterpenoids, sesquiterpenoid, flavonoids, phytosterol, and volatile oils. The present study is intended to understand the molecular-level interaction of phytoconstituents present in A. calcarata rhizomes with RA molecular targets using computational approaches. A total of 30 phytoconstituents reported from the plant were used to carry out docking with 36 known targets of RA. Based on the docking results, 4 flavonoids were found to be strongly interacting with the RA targets. Further, molecular dynamics simulation confirmed stable interaction of quercetin with 6 targets (JAK3, SYK, MMP2, TLR8, IRAK1, and JAK1), galangin with 2 targets (IRAK1 and JAK1), and kaempferol (IRAK1) with one target of RA. Moreover, the presence of these three flavonoids was confirmed in the A. calcarata rhizome extract using LC-MS analysis. The computational study suggests that flavonoids present in A. calcarata rhizome may be responsible for RA modulatory activity. Particularly, quercetin and galangin could be potential development candidates for the treatment of RA. Investigation of Alpinia calcarata constituent interactions with molecular targets of rheumatoid arthritis: docking, molecular dynamics, and network approach.

01 Oct 2020·Inflammation ResearchQ3 · MEDICINE

Transcriptomic analysis of hidradenitis suppurativa skin suggests roles for multiple inflammatory pathways in disease pathogenesis

Q3 · MEDICINE

Article

Author: Howell, Michael D ; Rumberger, Beth E ; Boarder, Erika L ; Owens, Sherry L

OBJECTIVEHidradenitis suppurativa (HS) is a chronic inflammatory disease with limited treatment options; therefore, the current study investigated the downstream signaling pathways that are differentially expressed in HS subjects and may drive disease pathogenesis.METHODSThe expression of 144 genes was evaluated in the skin of 16 healthy subjects and 34 subjects with mild to severe HS using QuantiGene Plex assay.RESULTSOne hundred and twenty-nine genes were significantly elevated in lesional HS skin as compared to the skin of healthy controls including pro-inflammatory cytokines (IL-1α, IL-6, TNF-α), IL-17-associated cytokines (IL-17A, IL-17F, IL-23A), the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, IL-24), and IFN family members (IFNA1, IFNB1, IFNG, IL-12B). This corresponded with increased expression of tyrosine kinases (JAK1, JAK3, BTK, SYK) and their downstream signaling partners (STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6).CONCLUSIONThese data illustrate the diverse immune activation in lesional HS skin and suggest that deeper interrogation of the disease heterogeneity may reveal unique opportunities for targeted therapies in designated subpopulations.

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