TLL-018 in Patients With Moderate to Severe Active Rheumatoid Arthritis With Inadequate Response or Intolerance to csDMARDs

NCT07748728 | Not Yet Recruiting Phase 2

• 1 other identifier: TLL-018-208
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled parallel-group Phase II study. The study aims to evaluate the efficacy and safety of TLL-018 in adult patients with moderate to severe active rheumatoid arthritis who have inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Conditions

Rheumatoid Arthritis (RA)

Keywords

TLL-018 tablet; Arthritis, Rheumatoid; Janus Kinase Inhibitors; Antirheumatic Agents; Drug Resistance; Treatment Failure

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

  Participants who met all of the following 3 conditions for improvement from baseline were classified as achieving the ACR20 response criteria: 1. ≥ 20% improvement in tender joint count (68 joints); 2. ≥ 20% improvement in swollen joint count (66 joints); and 3. ≥ 20% improvement in at least 3 of the following 5 parameters: 1. Physician's Global Assessment of Disease Activity (PGA); 2. Patient's Global Assessment of Disease Activity (PtGA); 3. Patient self-assessed pain (VAS); 4. Health Assessment Questionnaire Disability Index (HAQ-DI); 5. High-sensitivity C-reactive protein (hsCRP); C-reactive protein (CRP) is also acceptable.

  Week 12

Secondary Outcomes (13)

• Percentage of Participants With an American College of Rheumatology 20/50/70% (ACR20/50/70) Response

  Week 2 to Week 24 (ACR20, excluding Week 12)

• Change From Baseline in Disease Activity Score 28 (DAS28) (hsCRP)

  Baseline to Week 24

• Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(hsCRP)

  Week 2 to Week 24

• Percentage of Participants Achieving Clinical Remission Based on DAS28 (hsCRP)

  Week 2 to Week 24

• Change From Baseline in CDAI Scores

  Baseline to Week 24

Study Arms (2)

TLL-018 20mg

EXPERIMENTAL

TLL-018 20 mg, administered orally twice daily (BID) for 12 weeks during the double-blind treatment period. Eligible participants completing the double-blind phase may continue to receive TLL-018 in the subsequent 12-week open-label extension period.

Drug: TLL-018

Placebo

PLACEBO COMPARATOR

Matching placebo for TLL-018, administered orally twice daily (BID) for 12 weeks during the double-blind treatment period. Eligible participants completing the double-blind phase may transition to receive TLL-018 in the subsequent 12-week open-label extension period.

Drug: Placebo

Interventions

TLL-018 DRUG

Treatment group: TLL-018 20 mg BID in Period 1 → TLL-018 20 mg BID in Period 2

TLL-018 20mg

Placebo DRUG

Placebo group: Placebo BID in Period 1 → TLL-018 20 mg BID in Period 2

Placebo

Eligibility Criteria

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

You may qualify if:

• Aged 18 to 70 years inclusive, any sex; body mass index \[BMI = weight (kg)/height² (m²)\] ≤ 35 kg/m².
• "Meets the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for active rheumatoid arthritis (RA), with a disease duration of at least 3 months at the screening visit： Has received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for ≥ 3 months prior to screening, with a stable dose for at least 4 weeks before randomization； Active rheumatoid arthritis meeting all of the following criteria: ≥6 swollen joints (SJC, 66-joint count) and ≥6 tender joints (TJC, 68-joint count) at screening and baseline visits. Joints that have undergone major surgery or received intra-articular injection within 4 weeks before randomization will be excluded from SJC and TJC counts. High-sensitivity C-reactive protein (hsCRP) \> upper limit of normal (ULN) or ≥5 mg/L at baseline (CRP testing is acceptable; hsCRP is preferred)." 3 Functional Class I, II, or III according to the 1991 American College of Rheumatology (ACR) rheumatoid arthritis functional classification criteria.
• "Organ function must satisfy the following laboratory criteria: Bone marrow: hemoglobin ≥90 g/L; platelets ≥100 ×10⁹/L; absolute neutrophil count ≥1.5 ×10⁹/L; lymphocyte count ≥0.8 ×10⁹/L; white blood cell count ≥2.5 ×10⁹/L.
• Hepatic function: total bilirubin ≤1.5 × ULN; aspartate aminotransferase (AST) OR alanine aminotransferase (ALT) ≤1.5 × ULN.
• Renal function: serum creatinine \<1.2 × ULN. Urinalysis: urine protein ≤1+. If urine protein \>1+, a 24-hour urine protein collection is required, with total urinary protein ≤1 g." 5 Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding. A pregnancy test (e.g., β-HCG assay) must be performed prior to study entry (last menstrual period will be documented). All participants and their partners must agree to use effective contraception (as judged by the Investigator) from the first dose of investigational product until at least 90 days after the last dose (see Appendix 12). Participants must have no plans to donate sperm or ova from screening through at least 6 months after the last study drug administration.
• The participant understands the informed consent form, voluntarily agrees to participate in the study, and provides written informed consent. Informed consent must be obtained prior to performance of any study-related procedures.

You may not qualify if:

• Evidence or diagnosis of other rheumatic diseases prior to screening (secondary Sjögren's syndrome excluded), including systemic lupus erythematosus, psoriatic arthritis, mixed connective tissue disease, primary Sjögren's syndrome, dermatomyositis, polymyositis, systemic sclerosis, and ankylosing spondylitis.
• Presence of active fibromyalgia that, in the Investigator's judgment, may interfere with the evaluation of rheumatoid arthritis disease activity.
• Prior diagnosis of other systemic inflammatory diseases, including but not limited to juvenile chronic arthritis, inflammatory bowel disease, active vasculitis (excluding venous rheumatoid nodules), spondyloarthropathy, and psoriatic arthritis.
• Diagnosis of Felty's syndrome (rheumatoid arthritis with splenomegaly). 5 Presence of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, or cerebral diseases that, in the Investigator's opinion, would place the participant at unacceptable risk.
• A history of lymphoproliferative disorders (including but not limited to EBV-associated lymphoproliferative diseases, lymphoma, and leukemia), or presence of any current signs or symptoms suggestive of active lymphoproliferative disease.
• A previous history of severe hematological diseases such as aplastic anemia and myelodysplastic syndrome, or any disease condition that may cause hemolysis or erythrocyte instability, including malaria and hemolytic anemia.
• Current or previous history of thrombocytopenia, coagulation disorders, or platelet function disorders.
• History of cardiovascular or cerebrovascular events or surgeries within 12 months prior to screening, including but not limited to myocardial infarction, unstable angina, acute coronary syndrome, cerebral hemorrhage, cerebral infarction, coronary stent implantation, percutaneous transluminal coronary angioplasty, and coronary artery bypass grafting.
• History of thromboembolic events within 12 months prior to screening (e.g., pulmonary thromboembolism, deep vein thrombosis, mesenteric arterial embolism), or presence of current high thromboembolic risk factors, such as immobilization within 12 weeks before screening, congenital or hereditary thrombophilia, or antiphospholipid antibody syndrome.
• History of gastrointestinal perforation prior to screening (perforation caused by appendicitis or trauma is excluded).

Sponsors & Collaborators

• Hangzhou Highlightll Pharmaceutical Co., Ltd: lead

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 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

• Zeng Xiaofeng Zeng, PhD

  Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 6, 2026
• Study Start (Estimated): August 14, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 6, 2026

Record last verified: 2026-08

Locations

CN (1)