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

NCT05133297 | Completed Phase 2

• 1 other identifier: TLL-018-201
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants American College of Rheumatology 50% (ACR50) Response at Week 12

  A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥50% improvement in 68-tender joint count; * ≥50% improvement in 66-swollen joint count; and * ≥50% improvement in at least 3 of the 5 following parameters:

  Week 12

Secondary Outcomes (9)

• Number of Participants American College of Rheumatology 20% (ACR20) Response

  Week 4, 8, 12, 16, 20 and 24

• Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response

  Weeks 4, 8, 12, 16, 20 and 24

• Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response

  Weeks 4, 8, 12, 16, 20 and 24

• Change From Baseline in Disease Activity Score Based on 28-Joints Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP)

  Weeks 4, 8, 12, 16, 20 and 24

• Change From Baseline in Clinical Disease Activity Index (CDAI)

  Weeks 4, 8, 12, 16, 20 and 24

Study Arms (4)

Sequence 1

EXPERIMENTAL

TLL018 tablets, 1piece,BID

Drug: TLL-018

Sequence 2

EXPERIMENTAL

TLL018 tablets, 2pieces, BID

Drug: TLL-018

Sequence 3

EXPERIMENTAL

TLL018 tablets, 3pieces, BID

Drug: TLL-018

Sequence 4

ACTIVE COMPARATOR

TOFA tablets, 1pieces, BID

Drug: Tofacitinib

Interventions

TLL-018 DRUG

Oral tablets administered at dose1 BID daily for 24 weeks.

Also known as: Sequence 1

Sequence 1

Tofacitinib DRUG

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

Also known as: Sequence 4

Sequence 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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).
• 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.

You may not qualify if:

• History of Felty syndrome (Rheumatoid arthritis - Splenomegaly syndrome).
• A history of herpes zoster or disseminated herpes simplex.
• Treatment with any JAK inhibitor (tofacitinib, baricitinib, ruxolitinib) within 2 weeks prior to study start.
• Subjects have severe, progressive or uncontrollable symptoms of kidney, liver, blood, gastrointestinal, lung, cardiovascular, neurological or brain disease.
• 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.
• 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.
• Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody.
• Pregnant or breastfeeding female.

Sponsors & Collaborators

• Hangzhou Highlightll Pharmaceutical Co., Ltd: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100000, China

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: November 24, 2021
• Study Start: February 16, 2022
• Primary Completion: December 19, 2022
• Study Completion: May 30, 2023
• Last Updated: September 5, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)