Proximod, a Selective Sphingosine-1-phosphate Receptor 1 Modulator in Patients With Moderate-to-severe Active Rheumatoid Arthritis: a Double-blind, Randomised, Placebo-controlled, Phase 2 Trial.

NCT07335952 | Completed Phase 2 DMC

• 1 other identifier: 2024PHA083
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 20

Brief Summary

The goal of this multicenter, randomized, double-blind, placebo-controlled phase 2 clinical trial is to evaluate the efficacy and safety of proximod in active rheumatoid arthritis patients with inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The main questions it aims to answer are: Evaluate the efficacy of different doses of proximod in active RA patients who have inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and provide a basis for dose selection in the confirmatory phase III clinical study. Explore the changes of S1P and SPHK before and after treatment of proximod. Participants will take proximod 5mg/10mg daily or placebo for three months and will be followed up for 1 month.

Conditions

Rheumatoid Arthritis

Keywords

proximod; conventional synthetic disease-modifying antirheumatic drugs

Outcome Measures

Primary Outcomes (1)

• The proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12.

  The primary efficacy outcome

  Twelve weeks

Study Arms (3)

placebo

NO INTERVENTION

Patients will take placebo daily for three month

proximod 5mg daily

EXPERIMENTAL

Patients will take proximod 5mg daily for three months

Drug: proximod 5mg daily

proximod 10mg daily

EXPERIMENTAL

Patients will receive proximod 10mg daily

Drug: proximod 10mg daily

Interventions

proximod 5mg daily DRUG

Patients will take proximod 5mg daily

proximod 5mg daily

proximod 10mg daily DRUG

Patients will take proximod 10mg daily

proximod 10mg daily

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-70 years
• Diagnosed rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology- European League against Rheumatism classification criteria at least 3 months before screening.
• Have active RA as defined by ≥ 6 swollen joints (based on 66 joint counts) and ≥6 tender joints (based on 68 joint counts) at screening and baseline.
• High-sensitivity CRP concentrations equal to or exceeding the upper limit of normal value (ULN) or erythrocyte sedimentation rate (ESR) \> ULN
• Have an inadequate response to ≥ 1 csDMARDs, defined by moderate to high disease activity (DAS28 \>3.2, CDAI\>2.8, SDAI\>3.3).
• (1) Patients who received MTX treatment for at least 12 weeks before baseline, with no change in MTX dose (10-25 mg/week) for at least 4 weeks before baseline. For those who cannot tolerate a dose of ≥10 mg/week, a dose of ≥7.5 mg/week can be used.
• (2) Patients must discontinue all csDMARDs (excluding MTX) and must not use them during the study period. ① Minocycline, penicillamine, sulfasalazine,hydroxychloroquine, chloroquine, azathioprine, gold preparations, cyclophosphamide, tacrolimus, cyclosporine, Tripterygium wilfordii, etc., taken ≥4 weeks before the first administration of the investigational drug. ② For leflunomide used ≥12 weeks before the first administration of the study drug, cholestyramine (8 g, three times daily for 11 days) or activated charcoal (50 g every 6 hours for 24 hours) can be used for drug elimination. Moreover, the elimination drugs should be discontinued at least 2 weeks before the first administration of the study drug. ③ Other medications must be stopped at least 5 drug half - lives or ≥ 4 weeks before the first dose (whichever is longer).
• (3) Patients who have used MTX, discontinued MTX for at least 4 weeks. 6. For biological agents, such as: infliximab: Stop the drug for 8 weeks before the first dose; etanercept and tocilizumab: stop the drug for 4 weeks before the first dose; adalimumab, certolizumab, golimumab and abatacept: stop the drug for 10 weeks; rituximab: stop the drug for 6 month before the first dose.
• \. Female patients of childbearing potential and male patients must agree to use an effective method of contraception until at least 6 months after the last dose of Proximod.
• \. Sign an informed consent for the clinical study, willingness to comply with the study follow-up schedule and other requirements of the study protocol.

You may not qualify if:

• \. Allergic to any component of proximod. 2. Class IV according to the Classification of Global Functional Status in Rheumatoid Arthritis or wheelchair/bed-bound.
• \. Patients who are using one of the following treatment or medicine.
• An intra-articular or other injectable corticosteroid within 4 weeks prior to Screening
• Those who are using non-steroidal anti-inflammatory drugs (except paracetamol) and whose dosage has not been stable within 4 weeks before the first administration of the study drug, or those who cannot continue to take the drug at the original stable dosage during the trial. If they have stopped taking the drug, they need to stop taking the drug for at least 2 days or 5 half-lives (whichever is longer) before the first administration of the study drug.
• Patients who have received treatment with Iguratimod, interferon (such as Roferon, Intron A, Rebetron, etc.), drugs known to have strong immunosuppressive or immunomodulatory effects (including total Glucosides of Paeony, Tripterygium wilfordii Hook.f, mycophenolate mofetil, cyclosporine, tacrolimus, azathioprine, 6 - mercaptopurine, etc.), or technetium \[99Tc\] methylene diphosphonate injection within 4 weeks before the first administration of the study drug.
• Use of opioids within 4 weeks before the first administration of the study drug.
• Oral traditional Chinese medicines for the treatment of RA and other inflammatory diseases within 4 weeks before the first administration of the study drug.
• Subjects who have received integrin Alpha V antibodies or cell depletion therapy within 3 months before the first administration of the study drug or within 5 half - lives (whichever is longer).
• Received JAK inhibitors and/or S1P agonists within 5 half - lives or within 2 weeks (whichever is longer).
• Use of medications that interact with the study drug within 4 weeks or within 5 half - lives (whichever is longer).
• The subject has received live vaccines or live- attenuated vaccines within 4 weeks.
• Alcohol abuse or drug abuse, or there is a history of alcohol or drug abuse within 6 months before randomization.
• Patients who have participated in any interventional clinical trials of drugs or medical devices within the past three months.
• \. History or evidence of any of the following diseases:
• Those with any systemic inflammatory diseases/medical history other than RA (except secondary Sjögren's syndrome), including but not limited to inflammatory bowel disease (including Crohn's disease and ulcerative colitis), psoriatic arthritis, vasculitis, gout, systemic lupus erythematosus, axial spondyloarthritis (including ankylosing spondylitis and non-radiographic axial spondyloarthritis), reactive arthritis, scleroderma, polymyositis, dermatomyositis, fibromyalgia (with currently active symptoms), Felty syndrome.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (20)

Chun Li

Beijing, Beijing Municipality, 100044, China

Location

Guixiu Shi

Xiamen, Fujian, 361003, China

Location

Yi He

Guangzhou, Guangdong, 510630, China

Location

Mingwei Deng

Guangzhou, Guangdong, China

Location

Qingwen Wang

Shenzhen, Guangdong, 518036, China

Location

Ling Lei

Nanning, Guangxi, 530021, China

Location

Jiashun Zeng

Guiyang, Guizhou, 550004, China

Location

Mei Tian

Zunyi, Guizhou, 563099, China

Location

Xiaofei Shi

Luoyang, Henan, 471000, China

Location

Lingli Dong

Wuhan, Hubei, 430030, China

Location

Shulin Song

Yichang, Hubei, 43003, China

Location

Jian Wu

Suzhou, Jiangsu, 215006, China

Location

Senhua Dai

Pingxiang, Jiangxi, 337055, China

Location

Yanmei Wu

Panjin, Liaoning, 124000, China

Location

Xuebinwang

Binzhou, Shandong, 256603, China

Location

Weiqi Min

Heze, Shandong, 274006, China

Location

Hua Zhang

Zaozhuang, Shandong, 277100, China

Location

Zili Fu

Taiyuan, Shanxi, 030001, China

Location

Wubin Long

Chengdu, Sichuan, 610072, China

Location

Huaxiang Wu

Hangzhou, Zhejiang, 310009, China

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Zhanguo Li

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Rheumatology and Immunology

Model Details: Participants will be randomized in a 1:1:1 ratio to administer proximod 5mg daily, proximod 10mg daily or placebo.

Study Record Dates

• First Submitted: January 2, 2026
• First Posted: January 13, 2026
• Study Start: September 2, 2024
• Primary Completion: October 9, 2025
• Study Completion: October 9, 2025
• Last Updated: January 13, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning 1 year after publication with no end date

Locations

CN (20)