Clinical trial NCT06020144: A Phase 3 Study Comparing TLL-018 to Tofacitinib in RA Subjects With Inadequate Response or Intolerance to bDMARDs
Official title: A Phase 3, Randomized, Double-Blind, Positive-controlled, Head-to-Head Monotherapy Study Comparing TLL-018 to Tofacitinib in Subjects With Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-08-31
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

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);

Primary outcomes:
measure: Proportion of subjects achieving American College of Rheumatology 50% (ACR50) Response
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of subjects achieving DAS28-hsCRP <2.6
timeFrame: Week 24
measure: Proportion of subjects achieving American College of Rheumatology 20% (ACR20) and 70% (ACR70) Response
timeFrame: Week 24
measure: Change From Baseline in Disease Activity Score Based on 28-Joints Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP)
timeFrame: Week 24
measure: Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score
timeFrame: Week 24
measure: Changes From Baseline in SF-36 Score
timeFrame: Week 24
measure: Proportion of subjects achieving DAS28-hsCRP <＝3.2
timeFrame: Week 24
measure: Proportion of subjects achieving CDAI <＝10
timeFrame: Week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: