Amiselimod, a sphingosine 1-phosphate receptor-1 modulator, for systemic lupus erythematosus: A multicenter, open-label exploratory study.

Abstract

OBJECTIVE:

To evaluate the safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy of amiselimod, an oral selective sphingosine 1-phosphate receptor-1 modulator, in patients with systemic lupus erythematosus (SLE).

METHODS:

A multicenter, open-label phase Ib trial was conducted in Japan. Patients in Part 1 and Part 2-B received 0.2 mg amiselimod while those in Part 2-A received 0.4 mg amiselimod for 24 weeks.

RESULTS:

Seventeen subjects received 0.2 or 0.4 mg amiselimod. Amiselimod and amiselimod-P plasma concentrations increased dose-dependently. Peripheral blood lymphocyte count decreased in all patients after amiselimod treatment, with no clear dose response. There were no serious/severe adverse events (AEs) or clinically meaningful cardiac effects. Five subjects were withdrawn from amiselimod treatment following a decrease in lymphocyte count to <200/μl. Anti-double stranded-DNA antibody decreased from baseline to Week 24/end of treatment (EOT), with those in 2 subjects (22.2%) decreasing to within the normal range. Total SLE disease activity index 2000 score decreased by ≥4 at EOT in 7 of 17 subjects.

CONCLUSIONS:

Amiselimod was generally well tolerated. While no serious AEs or infectious AEs led to discontinuation, low lymphocyte counts of <200/μl were observed as a laboratory abnormality. Our findings suggest the potential efficacy of amiselimod for patients with SLE.Trial registration: ClinicalTrials.gov identifier: NCT02307643.

• Authors: Yoshiya Tanaka, Kazuoki Kondo, Ayako Ichibori, Yoshiari Yanai, Yutaka Susuta, Shinsuke Inoue, Tsutomu Takeuchi
• Journal: Lupus (Lupus) Vol. 29 Issue 14 Pg. 1902-1913 (Dec 2020) ISSN: 1477-0962 [Electronic] England
• PMID: 33115374 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)

Chemical References

• Autoantibodies
• Propanolamines
• Sphingosine-1-Phosphate Receptors
• amiselimod

Topics

• Adult
• Autoantibodies (drug effects)
• Double-Blind Method
• Female
• Humans
• Lupus Erythematosus, Systemic (drug therapy)
• Lymphocytes (drug effects)
• Male
• Middle Aged
• Non-Randomized Controlled Trials as Topic
• Propanolamines (administration & dosage, adverse effects, pharmacokinetics, pharmacology)
• Sphingosine-1-Phosphate Receptors (administration & dosage)