Filgotinib or lanraplenib in moderate to severe cutaneous lupus erythematosus: a phase 2, randomized, double-blind, placebo-controlled study

Abstract

Objectives: To explore the safety and efficacy of filgotinib (FIL), a Janus kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in cutaneous lupus erythematosus (CLE).

Methods: This was a phase 2, randomized, double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or FIL for up to 36 additional weeks.

Results: Of 47 randomized patients, 45 were treated (PBO, n = 9; LANRA, n = 19; FIL, n = 17). The primary endpoint [change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A score change from baseline was -5.5 (s.e. 2.56) with PBO, -4.5 (1.91) with LANRA and -8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater in select subgroups. A ≥5-point improvement in the CLASI-A score at week 12 was achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. A numerically greater proportion of patients in the FIL arm (50%) also achieved ≥50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most adverse events (AEs) were mild or moderate in severity. Two serious AEs were reported with LANRA and one with FIL.

Conclusion: The primary endpoint was not met. Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated.

Trial registration: ClinicalTrials.gov identifier NCT03134222.

Keywords: clinical trials and methods; cytokines and inflammatory mediators; inflammation; skin; systemic lupus erythematosus and autoimmunity.

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1

CLASI-A score least squares mean change from baseline to week 12 Full analysis set includes patients who were randomized and received at least one dose of study drug. Baseline value was the last available value collected on or prior to the day of the first dose of study drug. The adjusted means were obtained from a mixed effects model for repeated measures with baseline CLASI-A score, stratification factors, visit and treatment*visit as fixed effects and patient as a random effect.

Fig. 2

Secondary and exploratory endpoints (change from baseline or meeting criteria at week 12) (A) Secondary endpoints: proportion of patients with a ≥5-point improvement in the CLASI-A score (left) and proportion with no worsening in the CLASI-A score (right). (B) Exploratory endpoints: percentage of patients with ≥50% improvement in the CLASI-A score and patient- and physician-reported QoL assessments. Full analysis set includes patients who were randomized and received at least one dose of study drug. Increase in TSQM indicates improvement. DLQI: Dermatology Life Quality Index; TSQM: Treatment Satisfaction Questionnaire for Medication; VAS: Visual Analog Scale.

Fig. 3

Change in the CLASI-A score from baseline to week 12 by subgroup (A) Mean (95% CI) change from baseline for PBO, LANRA and FIL groups for selected subgroups. (B) Forest plot showing the median (Q1, Q3) for the PBO, LANRA and FIL groups for all subgroups. Age (in years) was calculated from date of first study drug administration. Disease subtype as reported in the clinical database was used for subgroup derivation. csDMARD subgroups determined per systemic DMARD use as reported in the clinical database. The following routes of administration were considered for systemic corticosteroids: oral, intravenous, intramuscular and subcutaneous. The duration of CLE was calculated based on the reported date of CLE diagnosis and the date of enrolment in the study. For all treatment groups, the baseline value was the last available value on or prior to the first dose of the study drug. *IFN activity was not a prespecified subgroup analysis. IFN activity was classified into subgroups according to whether the value was below (low) or above (high) the median value at baseline.