The primary objective of the study is to evaluate the long-term safety, tolerability, and efficacy of TLL-018 in patients with rheumatoid arthritis (RA) who have completed a preceding randomized controlled trial with TLL-018.
This is an open-label extension study to assess the long-term safety, tolerability, and efficacy of TLL-018 in adults with RA who have completed Study TLL-018-301(NCT06020144), a phase 3 randomized controlled trial with TLL-018. The study includes three parts: screening period, treatment period and follow-up period. All participants will be treated with TLL-018 20 mg twice daily (BID) for 78 weeks. Safety assessment will be conducted at 6, 12, 24, 36, 48, 60, 72, 78 weeks, including physical examination, collection of vital signs, laboratory tests, AEs, SAEs, etc. Efficacy evaluation will be performed at weeks 12, 24, 36, 48, 60, 72, and 78, including joint assessment, PGA, PtGA, VAS, HAQ-DI questionnaires, SF-36 scale, morning stiffness assessment, DAS28-hsCRP, CDAI, SDAI, ACR20/50/70 response assessment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
350
TLL-018 20 mg BID for 78 weeks
Peking Union Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
Number of occurrences and Percentage of Participants with AEs and SAEs
Evaluation includes vital signs, physical examination, ECG examination, laboratory tests, AE, SAE, etc.
Time frame: At Weeks 6, 12, 24, 36, 48, 60, 72, 78
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: \>=50% improvement in 68-tender joint count; \>=50% improvement in 66-swollen joint count; \>=50% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
Time frame: At Weeks 12, 24, 36, 48, 60, 72, 78
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: \>=20% improvement in 68-tender joint count; \>=20% improvement in 66-swollen joint count; \>=20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
Time frame: At Weeks 12, 24, 36, 48, 60, 72, 78
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria: \>=70% improvement in 68-tender joint count; \>=70% improvement in 66-swollen joint count; \>=70% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
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Time frame: At Weeks 12, 24, 36, 48, 60, 72, 78
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time
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.
Time frame: At Weeks 12, 24, 36, 48, 60, 72, 78
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time
The DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission is defined as a DAS28(CRP) score \< 2.6.
Time frame: At Weeks 12, 24, 36, 48, 60, 72, 78
Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time
The disease activity score-28-CRP (DAS28 \[CRP\]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores range from 0 to approximately 10 where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78
Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time
The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78
Change From Baseline in Simplified Disease Activity Index (SDAI) Over Time
The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78
Change From Baseline in Patient's Assessment of Pain Over Time
Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale from 0 to 100 mm. A score of 0 mm indicates "no pain" and a score of 100 mm indicates "worst possible pain."
Time frame: Baseline (of the preceding 301 study）and Weeks 12, 24, 36, 48, 60, 72, 78
Change From Baseline in Patient's Global Assessment of Disease Activity (PtGA) Over Time
The participant was asked to rate their current RA disease activity over the past 24 hours on a 100 mm VAS, where 0 mm indicates very low disease activity and 100 mm indicates very high disease activity.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78
Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Changes From Baseline in SF-36 Score
The physician rated the participant's current global RA disease activity (independently from the participant's assessment) on a visual analog scale (VAS) from 0 to 100 mm, where 0 mm indicates no disease activity and 100 mm indicates severe disease activity.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78
Changes From Baseline in SF-36 Score Over Time
SF-36 score was an evaluation of the functional status for a participant,taping eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Coded numeric values are recoded per the scoring key. All items are scored so that a high score defines a more favorable health state. Each item is scored on a o to 100 range. Items in the same scale are averaged together to create the 8 scale scores.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 24, 48, 78
Changes From Baseline in Morning Stiffness Over Time
The VAS is a 100 mm line ranging from 0 mm (no morning stiffness) on the left end and 100 mm (worst morning stiffness) on the right end. Subjects marked on the line to indicate their pain severity. The distance in mm was measured from the left end to the subject's marking. Duration of morning stiffness will be from wake-up time to time of resolution of morning stiffness.
Time frame: Baseline (of the preceding TLL-018-301 study）and Weeks 24, 48, 78