A 4-Week, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of the RXR Agonist Compound IRX4204 for the Treatment of Mild to Moderate Plaque Psoriasis

The goal of this clinical trial is to learn if IRX4204 works to treat plaque psoriasis in adults. It will also learn about the safety of IRX4204. The main questions it aims to answer are:
* Does IRX4204 treat plaque psoriasis symptoms?
* Does IRX4204 treat plaque psoriasis symptoms better than someone who is not being treated?
* What medical problems do participants have when taking IRX4204? Researchers will compare IRX4204 to a placebo (a look-alike substance that contains no drug) to see if the drug works to treat mild to moderate plaque psoriasis.
Participants will:
* Take IRX4204 every day for 28 days
* Visit the clinic once every week for checkups and tests
* Complete specific assessments about plaque psoriasis and changes to plaques

开始日期2025-03-01

申办/合作机构

Io Therapeutics, Inc.

NCT02991651 / Suspended临床1期

A Phase I Study of IRX4204 in Combination With Erlotinib in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer

Patient selection: a) Pathological confirmation of non-small cell lung cancer without activating EGFR mutations; b) Advanced stage disease (IV or IIIB with malignant effusion) with at least two prior chemotherapy regimens; c) No available curative therapy; d) Pregnant women are excluded; e) Informed consent.
Pretreatment evaluation: a) Medical history and physical examination; b) Hepatic and renal function (bilirubin, aspartate aminotransaminase, creatinine); c) Preoperative staging evaluation including CT-chest or PET/CT scan;
Treatment plan: Three dose levels of IRX4204 and erlotinib will be studied using intra-patient dose escalation for dose levels 1 and 2. These study agents will be administered orally until progression of disease, unacceptable toxicities, activation of a phase II study of the combination, or exhaustion of the IRX4204 drug supply.
Evaluation on study: Adverse events will be graded on a scale of 0 to 5, using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. Efficacy will be assessed using the RECIST v1.1 criteria based on CT-chest or PET/CT scan after 8 weeks of study treatment.

开始日期2016-05-01

申办/合作机构

Io Therapeutics, Inc.

[+1]

NCT02438215 / Completed临床1期

An Open-Label, Single Site Study Using [123I]β-CIT Single Photon Emission Tomography (SPECT) to Evaluate Dopamine Transporter Binding Following Treatment With IRX4204 in Early Parkinson's Disease Subjects

This is a single site, open-label study designed to examine dopamine transporter density using [123I]β-CIT SPECT imaging before and following treatment with IRX4204 for a 30-day period in early Parkinson's disease patients. In addition, clinical evaluations will be performed to evaluate the effect of IRX4204 treatment on the motor and cognitive symptoms of PD.

开始日期2014-08-01

申办/合作机构

Io Therapeutics, Inc.

100 项与 IRX-4204 相关的临床结果

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100 项与 IRX-4204 相关的转化医学

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100 项与 IRX-4204 相关的专利（医药）

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项与 IRX-4204 相关的文献（医药）

2024-06-03·Clinical cancer research : an official journal of the American Association for Cancer Research

IRX4204 Induces Senescence and Cell Death in HER2-positive Breast Cancer and Synergizes with Anti-HER2 Therapy

Article

作者: Vuligonda, Vidyasagar ; Coleman, Darian ; Brown, Powel H. ; Hill, Jamal ; Moyer, Cassandra L. ; Lanier, Amanda ; Mazumdar, Abhijit ; Sanders, Martin E. ; Qian, Jing

Abstract:

Purpose::

Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action.

Experimental Design::

IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models, and primary patient-derived xenograft (PDX) tumors. In vitro assays of cell cycle, apoptosis, senescence, and lipid metabolism were used to uncover a potential mechanism of action. Standard anti-HER2 therapies were screened in combination with IRX4204 on a panel of breast cancer cell lines to determine drug synergy.

Results::

IRX4204 significantly inhibits the growth of HER2-positive breast cancer cell lines, including trastuzumab and lapatinib–resistant JIMT-1 and HCC1954. Treatment with IRX4204 reduced tumor growth rate in the MMTV-ErbB2 mouse and HER2-positive PDX model by 49% and 44%, respectively. Mechanistic studies revealed IRX4204 modulates lipid metabolism and induces senescence of HER2-positive cells. In addition, IRX4204 demonstrates additivity and synergy with HER2-targeted mAbs, tyrosine kinase inhibitors, and antibody–drug conjugates.

Conclusions::

These findings identify HER2 as a biomarker for IRX4204 treatment response and demonstrate a novel use of RXR agonists to synergize with current anti-HER2 therapies. Furthermore, our results suggest that RXR agonists can be useful for the treatment of anti-HER2 resistant and metastatic HER2-positive breast cancer.

2023-08-03·Cells

RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.

Article

作者: Wang, Xiaobei ; Mathews, Parker ; Zhang, Min ; Kang, Yubin ; Wu, Jian

Retinoid X receptor (RXR) heterodimerizes with the PPAR nuclear hormone receptor and regulates its downstream events. We investigated the effects of RXR agonists (LG100754, bexarotene, AGN194204, and LG101506) on lenalidomide's anti-myeloma activity, T cell functions, and the level of glucose and lipids in vivo. Genetic overexpression and CRISPR/Cas9 knockout experiments were conducted in multiple myeloma (MM) cell lines and Jurkat T cell lines to determine the roles of CRBN in RXR-agonist mediated effects. A xenograft mouse model of MM was established to determine the combination effect of LG100754 and lenalidomide. The combination of RXR agonists and lenalidomide demonstrated synergistic activity in increasing CRBN expression and killing myeloma cells. Mechanistically, the RXR agonists reduced the binding of PPARs to the CRBN promoter, thereby relieving the repressor effect of PPARs on CRBN transcription. RXR agonists downregulated the exhaustion markers and increased the activation markers of Jurkat T cells and primary human T cells. Co-administration of LG100754 and lenalidomide showed enhanced anti-tumor activity in vivo. LG100754 retained its glucose- and lipid-lowering effects. RXR agonists demonstrate potential utility in enhancing drug sensitivity and T-cell function in the treatment of myeloma.

2018-08-01·Endocrinology

Retinoid X Receptor Activation During Adipogenesis of Female Mesenchymal Stem Cells Programs a Dysfunctional Adipocyte

Article

作者: Shoucri, Bassem M ; Hung, Victor T ; Chamorro-García, Raquel ; Shioda, Toshi ; Blumberg, Bruce

Abstract:

Early life exposure to endocrine-disrupting chemicals (EDCs) is an emerging risk factor for the development of obesity and diabetes later in life. We previously showed that prenatal exposure to the EDC tributyltin (TBT) results in increased adiposity in the offspring. These effects linger into adulthood and are propagated through successive generations. TBT activates two nuclear receptors, the peroxisome proliferator–activated receptor (PPAR) γ and its heterodimeric partner retinoid X receptor (RXR), that promote adipogenesis in vivo and in vitro. We recently employed a mesenchymal stem cell (MSC) model to show that TBT promotes adipose lineage commitment by activating RXR, not PPARγ. This led us to consider the functional consequences of PPARγ vs RXR activation in developing adipocytes. We used a transcriptomal approach to characterize genome-wide differences in MSCs differentiated with the PPARγ agonist rosiglitazone (ROSI) or TBT. Pathway analysis suggested functional deficits in TBT-treated cells. We then compared adipocytes differentiated with ROSI, TBT, or a pure RXR agonist IRX4204 (4204). Our data show that RXR activators (“rexinoids,” 4204 and TBT) attenuate glucose uptake, blunt expression of the antidiabetic hormone adiponectin, and fail to downregulate proinflammatory and profibrotic transcripts, as does ROSI. Finally, 4204 and TBT treatment results in an inability to induce markers of adipocyte browning, in part due to sustained interferon signaling. Taken together, these data implicate rexinoids in the development of dysfunctional white adipose tissue that could potentially exacerbate obesity and/or diabetes risk in vivo. These data warrant further screening and characterization of EDCs that activate RXR.

项与 IRX-4204 相关的新闻（医药）

2024-12-23

·GlobeNewswire-Health Care

Scientists report studies showing a novel drug repairs myelin and restores nervous system function in a model of multiple sclerosis

HALIFAX, Nova Scotia and SPRING, Texas, Dec. 23, 2024 (GLOBE NEWSWIRE) -- Scientists at Dalhousie University in Halifax, and Io Therapeutics, Inc. in Spring Texas, announced today collaborative publication of data from studies demonstrating effectiveness of the RXR agonist compound IRX4204 in reversing demyelination, and functionally restoring movement in the paralyzed legs of mice subjected to an autoimmune-mediated demyelinating model of human multiple sclerosis (MS). The research report titled: “Selective retinoid X receptor agonism promotes functional recovery and myelin repair in experimental autoimmune encephalomyelitis”, G.D.S Kasheke, et al; was published in the December 21, 2024 edition of Acta Neuropathologica Communications. IRX4204 selectively activates the retinoid X receptor (RXR). Given compelling links between RXR activation and increased myelin repair, the collaborating scientists employed IRX4204 to investigate the impact of RXR agonism on functional recovery in mice subjected to experimental autoimmune encephalomyelitis (EAE). EAE is a commonly used model of neuroinflammation in human MS. Machine learning was used to obtain highly sensitive and reliable measurements of hindleg movements for mice walking on a treadmill. IRX4204 not only blocked progressive loss of knee and ankle movements, but also reversed joint movement impairments in EAE mice. Biochemical, transcriptional and histological measurements in spinal cord supported that these gait improvements reflected increased axon survival, remyelination, and reduced inflammation. Using microglia, astrocytes and oligodendrocyte progenitor cells, additional data was obtained suggesting that IRX4204 acts on multiple glial subtypes to orchestrate myelin repair. George S. Robertson, Ph.D. is the lead scientist for these studies. He is a Professor in the Departments of Psychiatry and Pharmacology at Dalhousie University. His laboratory is located in the Brain Repair Centre at Dalhousie University. Dr. Robertson stated “These results inform the discovery of restorative neural therapeutics for MS by demonstrating that selective RXR agonism is sufficient for effective myelin repair. Moreover, our findings support the therapeutic potential of IRX4204 to promote functional neurologic recovery in MS, a long-sought therapeutic objective in the MS research community.” Martin E. Sanders, M.D., Chief Executive Officer of Io Therapeutics stated “The ability of IRX4204 to inhibit and functionally repair brain demyelination, while also inhibiting microglia-mediated brain inflammation in an MS model opens opportunities for potentially reparative treatment of brain damage in other types of neurologic conditions in which demyelination and microglial inflammation are demonstrated to play pathologic roles. Examples of such conditions include normal aging-related neurodegeneration, Alzheimer’s disease, Parkinson’s disease, traumatic injury, stroke, and schizophrenia. The company is planning to develop IRX4204 for multiple nervous system indications.” About Io Therapeutics: Io Therapeutics, Inc. is a privately held company headquartered in Spring, Texas. More information on Io Therapeutics and its product development programs is available on the company’s web site: www.io-therapeutics.com. Forward Looking Statements: This new release contains "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995.

2024-07-18

·药明康德

穿越血脑屏障小分子展现渐冻症治疗潜力！2期临床试验即将开展

Io Therapeutics今天公布其在研RXR核受体激动剂IRX4204的研究结果。分析显示，IRX4204能够恢复细胞抗自身免疫作用，促进髓鞘保护和修复，具穿越血脑屏障的能力，以及在人类中良好的安全性结果，支持其用于治疗肌萎缩侧索硬化症（ALS）的潜力。目前Io Therapeutics正在计划开展该药物用于ALS的相关2期试验。 ALS是一种逐渐衰弱并最终致命的神经退行性疾病，其病因和发病机制尚不完全清楚。过去研究发现，中枢神经系统（CNS）自身免疫失衡是是造成ALS患者的病理表征的原因之一，ALS患者体内的免疫抑制性Treg细胞过少，而促自身免疫性Th17细胞过多。此外，在部分ALS患者体内也观察到小胶质细胞介导的神经炎症和脱髓鞘（包围神经元的髓鞘丧失）现象。 Io Therapeutics所进行的临床前研究结果显示，在多种神经自身免疫动物模型中，IRX4204可促进人类Treg细胞生长并抑制人类Th17细胞生长，恢复其平衡，同时抑制神经退化，具有用于治疗ALS的潜力。在将自身免疫性Th17细胞转移至未患病小鼠的模型中，IRX4204在抑制神经自身免疫转移方面表现出100%的效果。在该模型中，受体小鼠的自身免疫神经炎症完全依赖于转移的自身免疫性Th17细胞的致病作用。实验结果显示，IRX4204抑制Th17细胞产生促炎细胞因子IL-17，并抑制CNS小胶质细胞产生的另一个重要促炎细胞因子IL-6。IRX4204还可促进少突胶质前体细胞成熟，并促进其生长为产生髓鞘的少突胶质细胞，从而修复受损的髓鞘。IRX4204在脱髓鞘小鼠模型中具有神经与髓鞘保护和髓鞘修复的作用。功能和组织病理学分析显示，IRX4204在多发性硬化症、帕金森病（PD）和阿尔茨海默病的动物模型中对多巴胺能和皮质神经元具有保护作用。目前IRX4204已经在1期和2期临床试验中对85名各种癌症患者和15名PD患者进行了长达20个月的持续治疗，并显示出口服给药的安全性和耐受性。在PD患者中，IRX4204显示能够穿越血脑屏障，并在开放标签评估中改善了患者的运动功能。基于IRX4204在Treg和Th17细胞上的平衡恢复抗自身免疫作用，促进少突胶质细胞成熟、髓鞘保护和修复作用，以及在人类中良好的安全性结果，Io Therapeutics决定开展IRX4204在ALS患者中的2期临床试验。参考资料： [1] Io Therapeutics, Inc., presented today results from studies of IRX4204, the company’s phase II clinical development stage, highly selective RXR nuclear receptor agonist compound, supporting its potential use for treatment of amyotrophic lateral sclerosis (ALS). Retrieved July 16, 2024 from https://www.globenewswire.com/news-release/2024/07/16/2913870/0/en/Io-Therapeutics-Inc-presented-today-results-from-studies-of-IRX4204-the-company-s-phase-II-clinical-development-stage-highly-selective-RXR-nuclear-receptor-agonist-compound-support.html 内容来源于网络，如有侵权，请联系删除。

临床2期临床结果

100 项与 IRX-4204 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11806

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
斑块状银屑病	临床2期	美国	Io Therapeutics, Inc.	2025-03-01
去势抵抗性前列腺癌	临床2期	美国	Io Therapeutics, Inc.	2011-08-01
非小细胞肺癌	临床2期	美国	Io Therapeutics, Inc.	-
晚期非小细胞肺癌	临床1期	美国	Io Therapeutics, Inc.	2016-05-01
帕金森病（青年型、早发型）	临床1期	美国	Io Therapeutics, Inc.	2014-08-01
HER2阳性乳腺癌	临床1期	美国	Io Therapeutics, Inc.	-
肌萎缩侧索硬化	临床前	美国	Io Therapeutics, Inc.	2024-12-01
关节炎	临床前	美国	Io Therapeutics, Inc.	2023-08-15
神经变性	临床前	美国	Io Therapeutics, Inc.	2023-08-15
阿尔茨海默症	临床前	美国	Io Therapeutics, Inc.	-

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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


NCT01540071 (CTgov)	临床2期	去势抵抗性前列腺癌	38	NRX 194204	範築壓鬱壓範簾積鹹獵(繭製網鹹蓋餘艱繭壓窪) = 構夢製獵窪憲範糧鹽膚鹽窪艱鹽獵簾餘遞築遞 (願顧壓顧壓觸簾廠糧遞, 鏇衊構獵顧積選壓廠網 ~ 簾繭廠鏇觸壓顧廠淵餘) 更多	-	2021-05-14
NCT01540071 (ASCO2014)	临床2期	转移性去势抵抗性前列腺癌	23	IRX4204 (20 mg/orally daily)	築簾築廠繭構獵艱淵壓(獵壓範觸築艱膚衊鬱願) = 齋糧壓廠鑰網鑰鏇蓋醖餘淵餘糧餘鏇鬱願膚壓 (構積糧夢鬱鬱構構觸獵 )	积极	2014-05-20
WPC2013	N/A	帕金森病	-	IRX4204	觸壓憲遞鹽膚顧壓繭繭(鏇醖鏇鏇廠窪選齋糧齋) = significant attenuation of PD-type motor impairments 衊襯齋築獵憲遞簾憲齋 (選鹽範醖觸鑰淵齋糧獵 ) 更多	-	2013-10-01
WPC2013	N/A	帕金森病	-	Placebo		-	2013-10-01