The Safety and Efficacy of TLL-018 in Active Rheumatoid Arthritis

NCT ID: NCT05133297

Last Updated: 2023-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-16
• Study Completion Date: 2023-05-30

Brief Summary

This is a randomized, double-blind, double-dummy, tofacitinib-parallel-group, phase 2A study to assess the safety and efficacy of TLL-018 in active rheumatoid arthritis subject who had an inadequate response or intolerance to methotrexate.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sequence 1

TLL018 tablets, 1piece,BID

Group Type: EXPERIMENTAL

TLL-018

Intervention Type: DRUG

Oral tablets administered at dose1 BID daily for 24 weeks.

Sequence 2

TLL018 tablets, 2pieces, BID

Group Type: EXPERIMENTAL

TLL-018

Intervention Type: DRUG

Oral tablets administered at dose2 BID daily for 24 weeks.

Sequence 3

TLL018 tablets, 3pieces, BID

Group Type: EXPERIMENTAL

TLL-018

Intervention Type: DRUG

Oral tablets administered at dose3 BID daily for 24 weeks.

Sequence 4

TOFA tablets, 1pieces, BID

Group Type: ACTIVE_COMPARATOR

Tofacitinib

Intervention Type: DRUG

Oral tablets administered at 5 mg BID daily for 24 weeks.

Interventions

TLL-018

Oral tablets administered at dose1 BID daily for 24 weeks.

Intervention Type: DRUG

TLL-018

Oral tablets administered at dose2 BID daily for 24 weeks.

Intervention Type: DRUG

TLL-018

Oral tablets administered at dose3 BID daily for 24 weeks.

Intervention Type: DRUG

Tofacitinib

Oral tablets administered at 5 mg BID daily for 24 weeks.

Intervention Type: DRUG

Other Intervention Names

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Eligibility Criteria

Inclusion Criteria

1. Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European League against Rheumatism (EULAR) criteria and have an inadequate response or intolerance to methotrexate.

2. Subjects must have been receiving oral or parenteral methotrexate therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit.

3. Have active RA as defined by the following minimum disease activity criteria:

• ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits;
• ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits;
• high-sensitivity C-reactive protein (hsCRP) > upper limit of normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (CCP) at Screening.

4. For subjects with inadequate response to methotrexate, subjects must have discontinued all oral disease-modifying anti-rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer:

• ≥4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide;
• ≥12 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal).

5. The organ function level must meet the following requirements:

Bone marrow: Blood routine results showed hemoglobin ≥90g/L, platelet ≥100×109/L, neutrophil absolute count ≥1.5×109/L; Liver: serum bilirubin ≤1.5 times the upper limit of normal value, aspartate aminotransferase (AST) ≤1.5 times the upper limit of normal value, alanine aminotransferase (ALT) ≤1.5 times the upper limit of normal value; Serum creatinine <1.5 times the upper limit of normal value; Urine protein ≤1+, if urine protein >1+, urine protein should be collected for 24 hours, the total amount should be ≤1 g. Female subjects of childbearing potential must test negative for pregnancy.

Exclusion Criteria

1. History of Felty syndrome (Rheumatoid arthritis - Splenomegaly syndrome).

2. A history of herpes zoster or disseminated herpes simplex.

3. Treatment with any JAK inhibitor (tofacitinib, baricitinib, ruxolitinib) within 2 weeks prior to study start.

4. Subjects have severe, progressive or uncontrollable symptoms of kidney, liver, blood, gastrointestinal, lung, cardiovascular, neurological or brain disease.

5. Current treatment or treatment within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study medication with another investigational medication or current enrollment in another investigational drug protocol.

6. If the laboratory T-Spot test (or other TB diagnostic test) is positive, the investigator will determine the activity based on the history and clinical manifestations, and the patients diagnosed as active TB should be excluded.

7. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody.

8. Pregnant or breastfeeding female.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hangzhou Highlightll Pharmaceutical Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

TLL-018-201

Identifier Type: -

Identifier Source: org_study_id