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)

Hangzhou Highlightll Pharmaceutical Co., Ltd1 site in 1 country450 target enrollmentNovember 15, 2023

ConditionsRheumatoid Arthritis

InterventionsTLL-018 Tofacitinib

DrugsTLL-018 Tofacitinib

Overview

Phase: Phase 3
Intervention: TLL-018
Conditions: Rheumatoid Arthritis
Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd
Enrollment: 450
Locations: 1
Primary Endpoint: Proportion of subjects achieving American College of Rheumatology 50% (ACR50) Response
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 15, 2023

End Date

September 30, 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hangzhou Highlightll Pharmaceutical Co., Ltd

Responsible Party

Sponsor

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；

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;

Arms & Interventions

sequence A

TLL018 tablets, 2piece,BID

Intervention: TLL-018

sequence B

Tofacitinib tablets, 1piece,BID

Intervention: Tofacitinib

Outcomes

Primary Outcomes

Proportion of subjects achieving American College of Rheumatology 50% (ACR50) Response

Time Frame: Week 24

ACR50 response: greater than or equal to (\>=) 50 percent (%) improvement in painful and tender joint count; \>= 50% improvement in swollen joint count; and \>= 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP)at each visit.

Secondary Outcomes

Proportion of subjects achieving DAS28-hsCRP <2.6(Week 24)
Proportion of subjects achieving American College of Rheumatology 20% (ACR20) and 70% (ACR70) Response(Week 24)
Change From Baseline in Disease Activity Score Based on 28-Joints Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP)(Week 24)
Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score(Week 24)
Changes From Baseline in SF-36 Score(Week 24)
Proportion of subjects achieving DAS28-hsCRP <＝3.2(Week 24)
Proportion of subjects achieving CDAI <＝10(Week 24)