AB0609 DESIGN OF A PHASE 2, DOUBLE-BLIND, PLACEBO-CONTROLLED, GLOBAL TRIAL OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYROSINE KINASE 2 (TYK2) INHIBITOR, IN PATIENTS WITH ACTIVE DISCOID AND/OR SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUS

Background

Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis ^[1,2]. Deucravacitinib demonstrated efficacy across multiple outcome measures, including achievement of ≥50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score (CLASI-50), in a phase 2 trial in patients with systemic lupus erythematosus (SLE) ^[3] and is being investigated in two phase 3 trials (NCT05617677; NCT05620407). Patients with discoid and/or subacute cutaneous lupus erythematosus (DLE/SCLE) have elevated expression of Type I interferons (IFN) ^[4]. Deucravacitinib mediates signaling of Type I IFN, IL-12, and IL-23 and may be an effective treatment for patients with DLE/SCLE ^[5].

Objectives

Results of this ongoing phase 2 trial (NCT04857034) will characterize the efficacy and safety of deucravacitinib compared with placebo in patients with active DLE/SCLE with or without SLE.

Methods

This phase 2, global, randomized, double-blind, placebo-controlled trial is enrolling adults (aged 18-75) with biopsy-confirmed clinical diagnosis of DLE/SCLE. Key eligibility criteria and study design are depicted below (Figure 1). Eligible patients will be randomized (1:1:1) to treatment with placebo or deucravacitinib (dose 1 or 2) for 16 weeks. At week 16, all patients randomized to placebo will be rerandomized (1:1) to treatment with deucravacitinib dose 1 or 2 until week 52. Patients originally randomized to deucravacitinib will continue treatment until week 52. The primary and secondary endpoints are depicted below (Table 1). This trial will also assess the safety and tolerability of 2 doses of deucravacitinib, exploratory efficacy endpoints, patient-reported outcomes, and pharmacodynamics.

Results

Planned enrollment is 75 total patients (25 per double-blind treatment group) in 8 countries in North and South America, Europe, and Asia-Pacific regions.

Conclusion

This phase 2 trial will characterize the efficacy, safety, and tolerability of deucravacitinib in patients with active DLE/SCLE.

References

[1]Armstrong A, et al. J Am Acad Dermatol. 2023;88(1):29-39. [2]Strober B, et al. J Am Acad Dermatol. 2023;88(1):40-51. [3]Morand E, et al. Arthritis Rheumatol. 2022 Nov 11 (Epub ahead of print). [4]Braunstein I, et al. Br J Dermatol. 2012;166(5):971-975. [5]Burke JR, et al. Sci Transl Med. 2019;11(502):eaaw1736.

Acknowledgements

This study was sponsored by Bristol Myers Squibb.

Disclosure of Interests

Victoria P. Werth Consultant of: Celgene, Medimmune, Resolve, Genentech, Idera, Janssen, Lilly, Biogen, Bristol Myers Squibb, Gilead, Amgen, Medscape, Nektar, Incyte, EMD Serono, CSL Behring, Principia, Crisalis, Viela Bio, Argenx, Kirin, AstraZeneca, AbbVie, GSK, Cugene, UCB, Corcept, and Beacon Bioscience, Grant/research support from: Celgene, Janssen, Biogen, Gilead, AstraZeneca, Viela, Amgen, and Lupus Research Alliance/BMS, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB., Jörg Wenzel Consultant of: GSK, Incyte, Spirig, AstraZeneca, Bristol Myers Squibb, Medac, Biogen, Novartis, LEO, Kyowa Kirin, Janssen, Bayer, Merck/Serono, Roche, Pfizer, ArrayBio, and Amgen, Nikolay Delev Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Harini Kothari Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Richard Meier Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shalabh Singhal Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Malavi Madireddi Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shimon Korish Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb.