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

Hangzhou Highlightll Pharmaceutical

Status and phase

Enrolling

Phase 3

Conditions

Rheumatoid Arthritis

Treatments

Drug: Tofacitinib

Drug: TLL-018

Study type

Interventional

Funder types

Industry

Identifiers

NCT06020144

TLL-018-301

Details and patient eligibility

About

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.

Full description

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.

Enrollment

450 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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);