A Phase 3 Study Comparing TLL-018 to Tofacitinib in RA Subjects With Inadequate Response or Intolerance to bDMARDs

• Status: Recruiting
• Trial end date: 2025-09-30
• Target enrollment: 0
• Participant gender: All

Summary

A randomized, double-blind, double-dummy, positive-controlled, phase 3 study to assess the safety and efficacy of TLL-018 in active rheumatoid arthritis subjects who had an inadequate response or intolerance to Biologic DMARDs.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd
• Treatments: Tofacitinib

Criteria

Inclusion Criteria:

• Aged between 18 and 65;

• Meet the diagnostic criteria of rheumatoid arthritis of the American College of Rheumatology/European Alliance against Rheumatism (ACR/EULAR,2010) with duration of at least 3 months;

• Meet the criteria for active rheumatoid arthritis；

• Have received at least one kind of bDMARDs for three months or longer and show inadequate response or intolerance to at least one kind of bDMARDs；

• Meet the ACR (1991) grading criteria of grade I, II or III；

• Discontinuation of bDMARDs or JAK inhibitors for more than four weeks；

• To sustain a stable status, oral administration of stable doses of glucocorticoids (≤ prednisone 10 mg/day or equivalent corticosteroids) and stable doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are allowed to use, provided that stable doses are maintained for at least one week prior to the study；

• BMI index is less than 35 kg/m2;

• Women of Child Bearing Potential (WOCBP) should not be pregnant or breastfeeding and the pregnancy test should be negative before randomization;

• Subjects (whether male or female) should have adequate barrier contraception during the whole treatment period and at least 90 days after treatment; subjects should avoid the sperm or ovum donation for at least six months after treatment；

• Subjects understand the informed consent form (ICF), volunteer for the study and sign the ICF;

Exclusion Criteria:

• With other rheumatic diseases;

• With other systemic inflammatory diseases;

• With progressive or uncontrolled symptoms of renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiovascular, neurologic, psychiatric, or cerebral disease;

• Previous history of severe hematologic diseases;

• Previous history of malignancy within five years, with exception of cured basal cell carcinoma or cutaneous squamous cell carcinoma or cervical carcinoma in situ.

• With active infection before randomization;

• Herpes zoster occurred within 1 year prior to randomization; disseminated or recurrent herpes zoster prior to randomization; disseminated herpes simplex before randomization;

• Previous history of active tuberculosis (TB) and no evidence of clinical cure or imaging evidence of active TB; or T-spot or PPD positive at screening but have received TB preventive therapy less than one month;

• HBsAg positive (or HBsAg negative but anti-HBc positive and HBV-DNA quantitative test positive), HCV antibody and HCV-RNA positive, or HIV antibody positive;

• Previous history of thrombocytopenia, coagulopathy, or platelet dysfunction;

• Previous history of cardiovascular and cerebrovascular accidents;

• Previous history of thromboembolism or risk factors;

• Previous history of gastrointestinal perforation;

• Temporary usage of NSAIDs within 24 hours prior to the baseline visit;

• Have received anti-rheumatic herb within 4 weeks before randomization;

• Have received interferon therapy within 4 weeks before randomization;

• Have donated blood more than 400 ml or received blood transfusion within 3 months prior to the study;

• Have received any live vaccine within 2 months before randomization or plan to receive a live vaccine during the study;

• Have experienced major surgery within 4 weeks before randomization, or expected to receive major surgical treatment after enrollment;

• Laboratory test results are abnormal and may interfere the study judged by investigators;

• Use of potent opioids within 4 weeks before the baseline visit;

• Allergy to ingredients or excipients of tofacitinib or TLL-018;

• Unable to accomplish evaluation in study;

• Receiving any study drug within 4 weeks or less than 5 elimination of half-life period) before randomization (whichever is longer);