BDMARDに対する反応が不十分または不耐性のRA被験者を対象にTLL-018とトファシチニブを比較する第3相試験 (TARA)
生物学的DMARD（bDMARD）に対する反応が不十分または不耐性の活動性関節リウマチ患者を対象に、TLL-018とトファシチニブを比較する第3相無作為化二重盲検陽性対照直接比較単剤療法試験
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Beijing Municipality
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Beijing、Beijing Municipality、中国
- Peking Union Medical College Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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；
- Subjects understand the informed consent form (ICF), volunteer for the study and sign the ICF;
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;
- Previous history of cardiovascular and cerebrovascular accidents;
- Previous history of thromboembolism or risk factors;
- Previous history of gastrointestinal perforation;
- Temporary usage of NSAIDs within 48 hours prior to the baseline visit;
- Have received anti-rheumatic herb within 4 weeks before randomization;
- Have received interferon therapy within 4 weeks before randomization;
- Have donated blood more than 400 ml or received blood transfusion within 3 months prior to the study;
- Have received any live vaccine within 2 months before randomization or plan to receive a live vaccine during the study;
- Have experienced major surgery within 4 weeks before randomization, or expected to receive major surgical treatment after enrollment;
- Laboratory test results are abnormal and may interfere the study judged by investigators;
- Use of potent opioids within 4 weeks before the baseline visit;
- Allergy to ingredients or excipients of tofacitinib or TLL-018;
- Unable to accomplish evaluation in study;
- Receiving any study drug within 4 weeks or less than 5 elimination of half-life period) before randomization (whichever is longer);
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：sequence A
TLL018 tablets, 2piece,BID |
Oral tablets administered 2pieces BID for 52 weeks.
他の名前：
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アクティブコンパレータ：sequence B
Tofacitinib tablets, 1piece,BID |
Oral tablets administered 1pieces BID for 52 weeks.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Proportion of subjects achieving American College of Rheumatology 50% (ACR50) Response
時間枠：Week 24
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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. |
Week 24
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Proportion of subjects achieving DAS28-hsCRP <2.6
時間枠：Week 24
|
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 patient'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. |
Week 24
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Proportion of subjects achieving American College of Rheumatology 20% (ACR20) and 70% (ACR70) Response
時間枠：Week 24
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ACR20/70 response: greater than or equal to (>=) 20/70 percent (%) improvement in painful and tender joint count; >= 20%/70% improvement in swollen joint count; and >= 20%/70% 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. |
Week 24
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Change From Baseline in Disease Activity Score Based on 28-Joints Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP)
時間枠：Week 24
|
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 patient'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. |
Week 24
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Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score
時間枠：Week 24
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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. |
Week 24
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Changes From Baseline in SF-36 Score
時間枠：Week 24
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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. |
Week 24
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Proportion of subjects achieving DAS28-hsCRP <＝3.2
時間枠：Week 24
|
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 patient'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. |
Week 24
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Proportion of subjects achieving CDAI <＝10
時間枠：Week 24
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Clinical Disease Activity Index equals the sum of score of following variables：Tender joint count (TJC28), Swollen joint count (SJC28), Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis |
Week 24
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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