a phase 3 study comparing tll-018 to tofacitinib in ra subjects with inadequate response or intolerance to bdmards

Conditions: Rheumatoid Arthritis

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.

this is a randomized, double-blind, double-dummy, tofacitinib-parallel-group, 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.

Eligibility 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);