Evaluation of proximod, a selective agonist of sphingosine-1-phosphate receptor-1, in healthy volunteers and patients with rheumatoid arthritis: a phase 1, double-blind, randomised, placebo-controlled, ascending dose trial

Zhang, H; Li, Q; Li, C; Wu, M; Chen, H; Li, Y; You, F; Zhao, Y; Jin, J; Chen, X; Ding, Y

doi:10.1016/s2665-9913(24)00199-1

Rheumatoid arthritis

Evaluation of proximod, a selective agonist of sphingosine-1-phosphate receptor-1, in healthy volunteers and patients with rheumatoid arthritis: a phase 1, double-blind, randomised, placebo-controlled, ascending dose trial

Lancet RheumatolPublished 22 Oct 2024Randomised controlled trial

Read the original article ↗PubMed

Cite

Authors' conclusion

Proximod exhibited good tolerability over the 28-day treatment period, demonstrating its potential in reducing blood lymphocyte count.

Study context

Population: Healthy volunteers (18–50 years, BMI 18–28 kg/m²) and patients with RA (18–70 years, BMI 18–30 kg/m²), single centre in Chinapart 1: 124

Comparison: Proximod vs placebo
Primary endpoint: Safety, tolerability and pharmacokinetic profile of proximod, in all treated participants
Follow-up: 72 days in healthy volunteers; 48 days in patients with RA

Methodological detailsphase 1, two part, double-blind, placebo-controlled, ascending dose, single-centre

Phase 1
Two part
Double-blind
Placebo-controlled
Ascending dose
Single-centre

Primary result

As reported in the abstract

Safety, tolerability and pharmacokinetics

Mean Ctrough proximod-phosphate day 28, 5 mg healthy volunteers

7.7 ng/mL

Mean Ctrough proximod-phosphate day 28, 5 mg RA

10.2 ng/mL

Mean Ctrough proximod-phosphate day 28, 10 mg RA

15.3 ng/mL

Further findings

Lymphocyte count, % decline from baseline at nadir (RA) · approximately day 28

Proximod 5 mg (RA, part 2)65.25%

Proximod 10 mg (RA, part 2)71.64%

Placebo20.57%

Safety

Adverse reactions, part 2

Healthy volunteers80%

RA patients92%

Adverse reactions, part 2 — Total adverse reactions reported: 74

Adverse reactions, part 2

Adverse events associated with proximod predominantly mild or moderate

Tolerability, part 1 (single ascending dose)

All doses well tolerated, with no dose-related adverse reactions or serious adverse events observed

Reference

Authors: Zhang H, Li Q, Li C, Wu M, Chen H, Li Y, et al.
All 11 authors
Zhang H, Li Q, Li C, Wu M, Chen H, Li Y, You F, Zhao Y, Jin J, Chen X, Ding Y
Journal: The Lancet Rheumatology
Published: 22 Oct 2024
DOI: 10.1016/s2665-9913(24)00199-1
PubMed: 39454617
Registration: NCT06361199, NCT06361186

Topic: Rheumatoid arthritis

Comparison

Proximod (single ascending doses in part 1; once-daily 5 mg or 10 mg for 28 days in part 2) vs placebo

Intervention details

Proximod single dose (part 1): single oral dose of proximod 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 1.5 mg, 2 mg, 3 mg, 5 mg, 10 mg, or 15 mg in cohorts 1-10, healthy volunteers

Key notes

Part 1: all doses well tolerated, no dose-related adverse reactions or serious adverse events
Part 2: EC50 of proximod-phosphate (6.1 ng/mL) reached on day 14 for both 5 mg groups, day 7 for 10 mg

Original publication

Evaluation of proximod, a selective agonist of sphingosine-1-phosphate receptor-1, in healthy volunteers and patients with rheumatoid arthritis: a phase 1, double-blind, randomised, placebo-controlled, ascending dose trial. Lancet Rheumatol. Published 22 October 2024. doi:10.1016/s2665-9913(24)00199-1

Read the original article ↗

Composed by AI from the published abstract and checked against it. How Briefs are made →