Efficacy and Safety of Ivarmacitinib Monotherapy in the Treatment of csDMARDs-IR Rheumatoid Arthritis

NCT07452445 | Not Yet Recruiting Phase 4

• 1 other identifier: TJ-IRB202512226
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting small joints, with a global prevalence of 0.5%-1.0% and 0.42% in China (around 5 million patients, mostly female and over 55). By 2050, RA patients worldwide are estimated to reach 31.7 million, an 80.2% increase from 2020. RA causes high disability rates, economic burdens, and can affect internal organs, leading to complications. Current treatments include csDMARDs (e.g., methotrexate, first-line but ineffective in half to two-thirds of patients), bDMARDs, tsDMARDs, NSAIDs, glucocorticoids, and traditional Chinese medicine. Studies have explored bDMARDs' efficacy in csDMARDs-IR patients. Switching to or adding upadacitinib improves ACR20 response rates, with monotherapy showing higher safety. Filgotinib also showed superior efficacy over placebo in methotrexate-IR patients. Ivarmacitinib, a novel JAK1 inhibitor, blocks cytokine signaling to reduce inflammation. A Phase II study (SHR0302-201) in moderate-to-severe RA patients showed ivarmacitinib 8 mg group had the highest ACR20 response rate (77.8%) after 12 weeks, with a dose-response relationship observed for ACR50/70 and DAS28-CRP improvements. TEAEs occurred in 73.9% of ivarmacitinib-treated patients, mostly infections, with upper respiratory tract infection being the most common. A Phase III study (SHR0302-301) also in moderate-to-severe RA patients showed similar results after 24 weeks, with the ivarmacitinib 8 mg group again having the highest ACR20 response rate (75.1%). AEs were comparable between placebo and ivarmacitinib 4 mg groups but higher in the 8 mg group, with upper respiratory tract infection, anemia, and hyperlipidemia being common. This project aims to investigate ivarmacitinib's therapeutic efficacy and safety in csDMARDs-IR RA patients, providing evidence for its use as a second-line treatment and exploring its effects at the single-cell sequencing and RNA-seq levels, offering new treatment options.

Conditions

Rheumatoid Arthritis

Keywords

csDMARDs-IR; RA; Ivarmacitinib

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving a 20% improvement in the American College of Rheumatology criteria (ACR 20) at Week 12.

  Week 12

Secondary Outcomes (14)

• Proportion of subjects achieving ACR 50

  Week 12 and 24

• Proportion of subjects achieving ACR 70

  Week 12 and 24

• Proportion of subjects with a Disease Activity Score in 28 joints (DAS28)-C-reactive protein (CRP) < 2.6;

  Week 12 and 24

• Proportion of subjects with a DAS28-CRP ≤ 3.2

  Week 12 and 24

• Changes in Clinical Disease Activity Index (CDAI) scores relative to baseline;

  Week 12 and 24

Study Arms (1)

Ivarmacitinib Monotherapy

EXPERIMENTAL

4-week screening period 12-week core treatment period: Emmacitinib 4mg group, oral administration, once daily. 12-week extended treatment period: Emmacitinib 4mg group or 8mg group, oral administration, once daily. 4-week follow-up period period

Drug: Ivarmacitinib

Interventions

Ivarmacitinib DRUG

4-week screening period 12-week core treatment period: Emmacitinib 4mg group, oral administration, once daily. 12-week extended treatment period: Emmacitinib 4mg group or 8mg group, oral administration, once daily. 4-week follow-up period period

Ivarmacitinib Monotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 and 75 years (inclusive) at the time of signing the informed consent form, regardless of gender;
• Meeting the diagnostic criteria for rheumatoid arthritis (RA) as defined in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for RA;
• Having moderate to severe active RA, defined as having a tender joint count (TJC) ≥ 6 or a swollen joint count (SJC) ≥ 6 based on a 68/66-joint count at screening, or a Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28 ESR)/C-reactive protein (CRP) ≥ 3.2, and having an ESR \> 28 mm/h or CRP/high-sensitivity CRP (hsCRP) \> 5 mg/L at screening;
• Having an inadequate response to or intolerance of at least one or more conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Subjects must have received regular csDMARD therapy for at least 3 months and have been on a stable dose for at least 4 weeks prior to initiating study drug treatment. Allowable csDMARDs include methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide, among others.

You may not qualify if:

• Requiring continued combination therapy with methotrexate (MTX), hydroxychloroquine, and sulfasalazine, or any combination of three csDMARDs;
• Subjects who have previously received a standard course of JAK inhibitors (e.g., tofacitinib, upadacitinib, baricitinib, filgotinib, deucravacitinib, etc., including topical formulations) and have primary failure to biologic DMARDs (bDMARDs) treatment;
• Subjects judged by the investigator to have active symptoms of primary fibromyalgia or other conditions that may interfere with the assessment of RA symptoms;
• Lactating or pregnant women, or fertile subjects unwilling to take effective contraceptive measures throughout the trial period and for 1 month after the last administration of emmacitinib tablets;
• Subjects with uncontrolled infections, such as hepatitis B carriers with liver dysfunction (aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of the laboratory normal range, or bilirubin ≥ 1.5 times the upper limit of the laboratory normal range); subjects with a history of latent or active tuberculosis who have not completed an adequate course of anti-tuberculosis treatment; subjects with symptomatic herpes zoster infection;
• Subjects with an estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m² calculated by the Modified Diet in Renal Disease (MDRD) formula or other methods;
• Subjects with moderate to severe congestive heart failure (New York Heart Association Class III or IV), or those who have experienced a cardiovascular or cerebrovascular event requiring hospitalization within 6 months prior to enrollment, including but not limited to percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, cerebral hemorrhage, or subarachnoid hemorrhage;
• Subjects with a current or history of malignancy (except for adequately treated or excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ);
• Subjects who have received a live/attenuated vaccine within the previous 3 months or are expected to receive a live/attenuated vaccine during the study period or within 28 days after the end of the study;
• Subjects who have participated in another clinical trial within 30 days prior to the screening period;
• Subjects who refuse to sign the informed consent form or are unwilling or unable to cooperate with the collection of medical history and clinical photographs;
• Subjects considered by the investigator to have any other conditions that make them unsuitable for participation in this study.

Sponsors & Collaborators

• Tongji Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ivarmacitinib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Lingli Prof. Dong, Ph.D.

CONTACT

+86-83663435; tjhdongll@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor;professor of medicine

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: March 5, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share