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Rheumatoid ArthritisPhase 2NCT05133297

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

A Phase 2 study testing TLL-018 and Tofacitinib in people with Rheumatoid Arthritis, run by Hangzhou Highlightll Pharmaceutical Co., Ltd at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
TLL-018 and Tofacitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
1 siteChina
Study dates
16 Feb 2022to 30 May 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100000

Other trials in China

About this study

Official title: A Phase 2A, Randomized, Double-blind, Double-dummy, Tofacitinib-parallel-group Study to Evaluate the Safety and Efficacy of TLL-018 in Active Rheumatoid Arthritis Who Had an Inadequate Response or Intolerance to Methotrexate.

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.

Being tested
TLL-018, Tofacitinib
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TLL-018Drug

    Also called Sequence 1

    Oral tablets administered at dose1 BID daily for 24 weeks.

  • TLL-018Drug

    Also called Sequence 2

    Oral tablets administered at dose2 BID daily for 24 weeks.

  • TLL-018Drug

    Also called Sequence 3

    Oral tablets administered at dose3 BID daily for 24 weeks.

  • TofacitinibDrug

    Also called Sequence 4

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

Study groups in NCT05133297
Study groupRoleWhat they receive
Sequence 1ExperimentalTLL018 tablets, 1piece,BID
Receives: Drug: TLL-018
Sequence 2ExperimentalTLL018 tablets, 2pieces, BID
Receives: Drug: TLL-018
Sequence 3ExperimentalTLL018 tablets, 3pieces, BID
Receives: Drug: TLL-018
Sequence 4Active comparatorTOFA tablets, 1pieces, BID
Receives: Drug: Tofacitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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:

    Measured: Week 12

Secondary outcomes (9)

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

    ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in painful and tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant 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.

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

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

    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: participant assessment of pain; participant 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.

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

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

    ACR70 response: greater than or equal to (>=) 70 percent (%) improvement in painful and tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant 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.

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

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

    Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014*participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Change = value at observation minus value at baseline.

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

  5. Change From Baseline in Clinical Disease Activity Index (CDAI)

    CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity as assessed by Multi-dimensional Health Assessment Questionnaire (MDHAQ) subscore, and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined. The range for the CDAI is 0 - 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity.

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

  6. Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score

    HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.

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

  7. Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score

    The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.

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

  8. Change From Baseline in Patient's Global Assessment of Arthritis

    Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm Visual Analog Scale where 0 = very well and 100 = very poorly. Change = score at observation minus score at baseline.

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

  9. Change From Baseline in Physician's Global Assessment of Arthritis

    Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity; very good and 100 mm = worst disease activity; very poor. Change = score at observation minus score at baseline.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2021
  2. Study start16 Feb 2022
  3. Primary completion19 Dec 2022
  4. Study completion30 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05133297
Sponsor's protocol ID
TLL-018-201
Status last verified
Sep 2023
First submitted
15 Nov 2021
Last updated
5 Sep 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TLL-018 and Tofacitinib in people with Rheumatoid Arthritis, run by Hangzhou Highlightll Pharmaceutical Co., Ltd at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants American College of Rheumatology 50% (ACR50) Response at Week 12 (time frame: Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05133297.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2023.

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