A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of R333 6% Ointment Administered Topically to Discoid Lupus Erythematosus (DLE) and Systemic Lupus Erythematosus (SLE) Patients With Active Cutaneous Discoid Lesions

The purpose of this study is to determine the safety, efficacy and tolerability of topical R333 ointment in Discoid Lupus Erythematosus (DLE) and Systemic Lupus Erythematosus (SLE) patients with active discoid lesions.

Start Date01 Aug 2012

Sponsor / Collaborator

Rigel Pharmaceuticals, Inc.

100 Clinical Results associated with R-333

100 Translational Medicine associated with R-333

100 Patents (Medical) associated with R-333

Literatures (Medical) associated with R-333

01 Dec 2020·Clinical Reviews in Allergy & ImmunologyQ2 · MEDICINE

JAK Inhibitors: Prospects in Connective Tissue Diseases

Q2 · MEDICINE

Review

Author: Zhao, Jiuliang ; Li, Jing ; You, Hanxiao ; Zeng, Xiaofeng ; Li, Mengtao ; Wang, Qian ; Tian, Xinping ; Xu, Dong

The dysregulation of the JAK-STAT pathway is associated with various immune disorders. Four JAK inhibitors have been approved for rheumatoid arthritis (RA), and numerous JAK inhibitors are currently being tested in phase II and III trials for the treatment of various autoimmune inflammatory diseases. In this narrative review, we elucidate the involvement of the JAK-STAT signaling pathway in the pathogenesis of connective tissue diseases (CTDs). We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, solcitinib, itacitinib, decernotinib, R333, and pf-06651600) for CTDs including RA, systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjögren's syndrome, and vasculitis, based on laboratory and clinical research findings. JAK inhibitors have great potential for the treatment of various CTDs by reducing multiple cytokine production and suppressing inflammation, with the advantages of rapid onset in an oral formulation and decreased corticosteroid dependence and the associated adverse events, especially in refractory cases. We also highlight the safety of novel JAK inhibitors, which can cause opportunistic infections, especially viral infections. Being a very recent therapeutic option, information regarding the safety of JAK inhibitors during pregnancy and for pediatric use is limited. However, it is recommended that JAK inhibitors should be avoided in pregnant and breastfeeding women. More clinical data, especially on highly selective inhibitors, are required to judge the efficacy and safety of JAK inhibition in CTDs.

01 Jun 2018·British Journal of Dermatology

Computerized planimetry to assess clinical responsiveness in a phase II randomized trial of topical R333 for discoid lupus erythematosus

Article

Author: Presto, J.K. ; Werth, V.P. ; Furie, R. ; Okon, L.G. ; Feng, R. ; Fiorentino, D. ; Wallace, D.J.

BACKGROUNDR333 is a topical janus kinase and spleen tyrosine kinase inhibitor being evaluated for discoid lupus erythematosus (DLE) treatment. There is no validated measure to assess the area of active DLE lesions.OBJECTIVESTo evaluate R333 efficacy and assess a technique to measure responsiveness.METHODSFifty-four patients with DLE were randomized in a double-blind design to R333 or placebo. Primary end point was the proportion of patients achieving ≥ 50% decrease in erythema and scale based on lesional Cutaneous Lupus Erythematosus Disease Area and Severity Index^TM for all treated lesions at week 4. Two-dimensional (2D) area measurements for each lesion were recorded at baseline and weeks 1-6. Eighty-eight photographs (44 pre- and 44 post-treatment) were obtained from the trial and change in size of active areas was analysed by computerized planimetry and physician-assessed area change (PAAC).RESULTSThirty-six patients were randomized to R333 and 18 patients were randomized to placebo. Primary end point was not achieved. There was a strong association between lesion activity and physician global assessment (P < 0·001). Photos of 42 patients assessed by computerized planimetry demonstrated excellent inter- and intra-rater reliability. Area change by computerized planimetry showed a strong correlation with PAAC (Spearman r = 0·72). Area change by 2D measurements showed a weak correlation with PAAC (Spearman r = 0·29).CONCLUSIONSFour weeks of R333 treatment did not result in significant improvement in lesion activity. Lesion activity and area change using computerized planimetry are better determinants of responsiveness than area change using 2D measurements.

01 Oct 2011·The Journal of ImmunologyQ2 · MEDICINE

IL-2 Regulates Expression of C-MAF in Human CD4 T Cells

Q2 · MEDICINE

Article

Author: Kanhere, Aditi S. ; Tewolde-Berhan, Lemlem ; Afzali, Behdad ; Kelly, Audrey ; Ragheb, Jack A. ; Cousins, David J. ; Lavender, Paul ; John, Susan ; Pedroza-Pacheco, Isabela ; Rani, Aradhana ; Jenner, Richard G. ; Hackett, Mark ; Jurcevic, Stipo ; Bowen, Holly

AbstractBlockade of IL-2R with humanized anti-CD25 Abs, such as daclizumab, inhibits Th2 responses in human T cells. Recent murine studies have shown that IL-2 also plays a significant role in regulating Th2 cell differentiation by activated STAT5. To explore the role of activated STAT5 in the Th2 differentiation of primary human T cells, we studied the mechanisms underlying IL-2 regulation of C-MAF expression. Chromatin immunoprecipitation studies revealed that IL-2 induced STAT5 binding to specific sites in the C-MAF promoter. These sites corresponded to regions enriched for markers of chromatin architectural features in both resting CD4 and differentiated Th2 cells. Unlike IL-6, IL-2 induced C-MAF expression in CD4 T cells with or without prior TCR stimulation. TCR-induced C-MAF expression was significantly inhibited by treatment with daclizumab or a JAK3 inhibitor, R333. Furthermore, IL-2 and IL-6 synergistically induced C-MAF expression in TCR-activated T cells, suggesting functional cooperation between these cytokines. Finally, both TCR-induced early IL4 mRNA expression and IL-4 cytokine expression in differentiated Th2 cells were significantly inhibited by IL-2R blockade. Thus, our findings demonstrate the importance of IL-2 in Th2 differentiation in human T cells and support the notion that IL-2R–directed therapies may have utility in the treatment of allergic disorders.

100 Deals associated with R-333

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Lupus Erythematosus, Discoid	Phase 2	US	Rigel Pharmaceuticals, Inc.	01 Aug 2012
Lupus Erythematosus, Discoid	Phase 2	CA	Rigel Pharmaceuticals, Inc.	01 Aug 2012
Nummular eczema	Phase 2	CA	Rigel Pharmaceuticals, Inc.	01 Aug 2012
Nummular eczema	Phase 2	US	Rigel Pharmaceuticals, Inc.	01 Aug 2012
Systemic Lupus Erythematosus	Phase 2	US	Rigel Pharmaceuticals, Inc.	01 Aug 2012
Systemic Lupus Erythematosus	Phase 2	CA	Rigel Pharmaceuticals, Inc.	01 Aug 2012
Vaccination	Phase 2	US	Rigel Pharmaceuticals, Inc.	01 Aug 2012
Vaccination	Phase 2	CA	Rigel Pharmaceuticals, Inc.	01 Aug 2012

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01597050 (SKINDLE, CTgov)	Phase 2	Nummular eczema \| Systemic Lupus Erythematosus \| Vaccination \| Lupus Erythematosus, Discoid	54	R932333 (Drug: R932333)	hxzgfwxsps(acrrywfhqd) = jrgsyrftle ekxukyqfvq (sgvujfiobd, ygiicuycds - aptkgcxouo) View more	-	08 Jun 2016
				Placebo (Placebo)	hxzgfwxsps(acrrywfhqd) = miqupdneqa ekxukyqfvq (sgvujfiobd, ihfwjacrou - leoehmqsfw) View more

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