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EADV 2020 | Results From RIST4721-201, a Randomized, Double-Blind, Placebo Controlled Exploratory Phase 2a Study in Subjects with Palmoplantar Pustulosis

Presented by Robert Bissonnette MD, FRCPC

A report from the 29th Congress of the European Academy of Dermatology and Venereology 

 
Intro and design: RIST4721 is an oral small molecule CXC chemokine receptor 2 (CXCR2) antagonist. This study assessed RIST4721 300mg daily vs placebo in palmoplantar psoriasis, with primary endpoint of change from baseline in fresh pustules and total pustules at week 4.

Results: Primary endpoint was not significant, but post-HOC analysis in subgroup with progressing disease showed statistically significant results (p < 0.05) as follows:

  • PPPASI 50% reduction: achieved by 71% in RIST (n = 5/7) vs 15% in placebo (n = 2/13)
  • Target palm or sole pustule count; -29.0 in RIST (n = 7) vs -3.5 in placebo (n= 13)
  • Significant pharmacodynamic results in RIST arm included: decrease in circulating neutrophils, decrease in T-cell activation markers, and increase in IL-8 levels.
Adverse effects: More treatment emergent AEs in RIST than placebo (86.7% vs 36.8%); most were mild (mainly gastrointestinal or musculoskeletal), with no severe AEs or deaths

Conclusion: RIST is a potent small molecule CXCR2 antagonist with potential as novel oral treatment for neutrophil diseases; further studies are needed to assess its potential efficacy.

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