Session Information
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Effector memory T cells of both CD4 and CD8 lineages are key drivers of autoimmunity and are pathogenic in several autoimmune diseases including psoriasis, atopic dermatitis, lupus nephritis, and inflammatory bowel disease among others by both human clinical and animal experimental data. Kv1.3 is a potassium channel required for sustained intracellular calcium influx, proliferation and activation of effector memory T cells. Dalazatide (ShK-186) is a potent, highly specific, first-in-class peptide blocker of Kv1.3 and effector memory T cells. Here we report on the safety, tolerability, pharmacodynamics and immunomodulating proof-of-concept data for dalazatide from a phase Ib study in patients with active plaque psoriasis.
Methods: A double blind trial was conducted in patients with active mild to moderate plaque psoriasis. Cohorts received either 30 mcg (n=10), 60 mcg (n=10 or placebo (n=4) twice weekly subcutaneous injections for 4 weeks with 4 weeks of follow up. Skin lesion biopsies were collected at baseline and at week 4 post treatment for gene expression and immunohistological analyses. Plasma, serum and peripheral blood mononuclear cells were collected at baseline and at several times during the study. Target lesions were evaluated at baseline and at day 32.
Results: The treatment was well tolerated with all subjects completing the study and reporting only mild adverse events. 50% of subjects in 60 mcg group achieved clinical improvement in target lesion. Improvements were observed as early as day 15 and for up to 4 weeks following last dose (day 57, end-of-study). Ongoing improvement continued during follow-up period in some subjects. 90% of subjects in 60 mcg group had reduction in PASI score.
Conclusion: These results demonstrate that twice weekly subcutaneous dosing of Kv1.3 blocker dalazatide is safe and well tolerated in psoriasis patients. Improvement in clinical disease endpoints provides proof-of-concept data for the immunomodulating mechanism of action of dalazatide in a prototypical T cell mediated autoimmune disease
To cite this abstract in AMA style:
Munoz-Elias EJ, Peckham D, Norton K, Duculan J, Cueto I, Li X, Qin J, Lustig K, Tarcha E, Odegard J, Krueger JG, Iadonato SP. Dalazatide (ShK-186), a First-in-Class Blocker of Kv1.3 Potassium Channel on Effector Memory T Cells: Safety, Tolerability and Proof of Concept of Immunomodulation in Patients with Active Plaque Psoriasis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/dalazatide-shk-186-a-first-in-class-blocker-of-kv1-3-potassium-channel-on-effector-memory-t-cells-safety-tolerability-and-proof-of-concept-of-immunomodulation-in-patients-with-active-plaque-psori/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/dalazatide-shk-186-a-first-in-class-blocker-of-kv1-3-potassium-channel-on-effector-memory-t-cells-safety-tolerability-and-proof-of-concept-of-immunomodulation-in-patients-with-active-plaque-psori/