A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis

Robert Bissonnette, Catherine Maari, Athanasios Tsianakas, DeAnne Reid, Sara McCutchan, Scott Baumgartner, James Mackay, Nihar Bhakta, Robert Bissonnette, Catherine Maari, Athanasios Tsianakas, DeAnne Reid, Sara McCutchan, Scott Baumgartner, James Mackay, Nihar Bhakta

Abstract

Introduction: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition with neutrophilic infiltration of the epidermis. RIST4721 antagonizes CXC chemokine receptor type 2, which is important in neutrophil recruitment and migration. In this study, the efficacy and safety of RIST4721 versus placebo were assessed in adult subjects with moderate to severe PPP.

Methods: This phase 2a, multicenter, randomized, double-blind, placebo-controlled study investigated RIST4721 versus placebo in subjects with moderate to severe PPP. Key eligibility criteria included: Palmoplantar Pustulosis Area and Severity Index (PPPASI) ≥ 8 and Palmoplantar Pustulosis Physician Global Assessment ≥ 3. Subjects were randomized 1:1 to RIST4721 300 mg or placebo once daily for 28 days. The primary efficacy endpoints were relative change from baseline in fresh and total pustule count at day 28.

Results: Fifteen subjects received RIST4721 and 19 subjects received placebo. Treatment with RIST4721 was found to be generally well tolerated. At day 28, the mean ± standard deviation (SD) relative change from baseline in fresh pustule count was 0.86 ± 0.692 and 0.53 ± 0.561 (P = 0.240) and in total pustule count was 0.99 ± 0.667 and 0.96 ± 0.672 (P = 0.804) for RIST4721 and placebo groups, respectively. Subgroup analysis of subjects with progressing disease demonstrated that subjects with a PPPASI-50 at day 28 was significantly higher for subjects treated with RIST4721 (71%) than placebo (15%) (P = 0.022).

Conclusion: Preliminary data suggest RIST4721 is well tolerated and may be a potential therapy for patients with PPP.

Trial registration: RIST4721-201 was registered in June 2019 at clinicaltrials.gov: NCT03988335.

Keywords: CXCR2; Neutrophils; Palmoplantar pustulosis; Pustules; RIST4721.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT diagram. mITT modified intent to treat
Fig. 2
Fig. 2
Absolute change in neutrophils. D day, f/u follow-up
Fig. 3
Fig. 3
Relative change from baseline in fresh pustule count by visit. LS means, two-sided 90% CIs, and P-values are from a MMRM analysis on relative change from baseline in fresh pustule count. The model includes treatment, visit (days 7, 14, 21, and 28), and treatment-by-visit interaction as fixed effects and the baseline value as covariate. CI confidence interval, LS least squares, MMRM mixed model for repeated measurements
Fig. 4
Fig. 4
Relative change from baseline in total pustule count by visit. LS means, two-sided 90% CIs, and P-values are from a MMRM analysis on relative change from baseline in total pustule count. The model includes treatment, visit (days 7, 14, 21, and 28), and treatment-by-visit interaction as fixed effects and the baseline value as covariate. CI confidence interval, LS least squares, MMRM mixed model for repeated measurements
Fig. 5
Fig. 5
Post hoc analysis of subgroup of subjects achieving PPPASI-50 at day 28. T-test analysis of subgroup of subjects with progressing disease who had an increase in total pustule count between screening and baseline. PPPASI Palmoplantar Pustulosis Psoriasis Area and Score Index, PPPASI-50 50% reduction in PPPASI
Fig. 6
Fig. 6
Proportion of subjects achieving PPPASI-50 at any time. T-test analysis of the proportion of subjects was conducted. PPPASI Palmoplantar Pustulosis Psoriasis Area and Score Index, PPPASI-50 50% reduction in PPPASI

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Source: PubMed

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