Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis (986)
A 24-week Phase IIb, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Tregalizumab (BT061) in Combination With Methotrexate in the Treatment of Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Alone, Followed by a 24-week Extension Phase: T Cell REgulating Arthritis Trial 2b (TREAT 2b)
The purpose of this study is to determine the efficacy and safety of three different Tregalizumab doses in combination with Methotrexate (MTX) in subjects who have active rheumatoid arthritis and an inadequate response to MTX alone.
The overall study duration is 24 weeks followed by a 24 week extension phase.
調査の概要
詳細な説明
The planned clinical study 986 (TREAT 2b) is a 24-week study in patients with Active rheumatoid arthritis (RA) who have had an inadequate response to Methotrexate (MTX) alone. The main phase of this study is followed by a 24-week extension phase for subjects meeting the respective entry criteria. Patients will be randomized to one of three different Active treatment groups or Placebo. The primary efficacy variable is the proportion of subjects with an ACR20 response after 12 weeks of double blinded treatment with the study medication based on observed cases in the FAS.
At Week 12, all subjects who had a minimum improvement of at least 20% (from baseline) in their tender joint count (TJC) and swollen joint count (SJC) continued on the same treatment. Subjects who had not demonstrated an improvement of at least 20% of TJC and SJC were assessed as non-responders. Non-responders who received placebo were randomized to an active treatment dose in a blinded manner. Non-responders who received active treatment were rolled up to the next highest dose in a blinded manner, apart from those already on the highest dose. These subjects remained on the highest dose.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Arizona
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Paradise Valley、Arizona、アメリカ、85253
- Study Site 07
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Illinois
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Springfield、Illinois、アメリカ、62704
- Study site 01
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Nebraska
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Lincoln、Nebraska、アメリカ、68516
- Study site 03
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New Jersey
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Clifton、New Jersey、アメリカ、07012
- Study site 02
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South Carolina
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North Charleston、South Carolina、アメリカ、29406
- Study site 04
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Tennessee
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Jackson、Tennessee、アメリカ、38305
- Study site 05
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Texas
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Houston、Texas、アメリカ、77004
- Study site 09
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Katy、Texas、アメリカ、77450
- Study site 10
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Donetsk、ウクライナ
- Study Site 08
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Kharkiv、ウクライナ
- Study site 01
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Kharkiv、ウクライナ
- Study site 02
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Kyiv、ウクライナ
- Study site 03
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Kyiv、ウクライナ
- Study site 04
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Vinnytsia、ウクライナ
- Study site 05
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Vinnytsia、ウクライナ
- Study site 06
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Vinnytsia、ウクライナ
- Study Site 07
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Zaporizhzhia、ウクライナ
- Study site 09
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Tallinn、エストニア
- Study site 01
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Quebec
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Rimouski、Quebec、カナダ
- Study site 02
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St-Jérôme、Quebec、カナダ
- Study site 01
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Bratislava、スロバキア
- Study site 03
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Kosice - Saca、スロバキア
- Study site 04
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Lucenec、スロバキア
- Study site 05
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Povazska Bystrica、スロバキア
- Study site 02
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Rimavska Sobota、スロバキア
- Study site 01
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Belgrade、セルビア
- Study site 01
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Belgrade、セルビア
- Study site 02
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Belgrade、セルビア
- Study site 04
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Niska Banja、セルビア
- Study site 03
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Bruntal、チェコ
- Study site 03
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Ostrava、チェコ
- Study site 05
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Praha、チェコ
- Study site 01
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Praha、チェコ
- Study site 04
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Praha、チェコ
- Study Site 08
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Praha、チェコ
- Study site 09
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Uherske Hradiste、チェコ
- Study site 02
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Uherske Hradiste、チェコ
- Study Site 07
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Zlin、チェコ
- Study site 06
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Berlin、ドイツ
- Study site 03
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Frankfurt、ドイツ
- Study site 04
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Muenchen、ドイツ
- Study site 06
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Ratingen、ドイツ
- Study site 02
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Zerbst、ドイツ
- Study site 01
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Balatonfüred、ハンガリー
- Study site 03
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Budapest、ハンガリー
- Study site 02
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Budapest、ハンガリー
- Study site 04
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Budapest、ハンガリー
- Study site 05
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Gyula、ハンガリー
- Study site 06
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Veszprem、ハンガリー
- Study site 01
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Plovdiv、ブルガリア
- Study site 01
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Plovdiv、ブルガリア
- Study site 06
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Sofia、ブルガリア
- Study site 02
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Sofia、ブルガリア
- Study site 04
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Sofia、ブルガリア
- Study Site 07
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Stara Zagora、ブルガリア
- Study site 05
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Varna、ブルガリア
- Study site 03
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Bialystok、ポーランド
- Study Site 08
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Bydgoszcz、ポーランド
- Study site 05
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Elblag、ポーランド
- Study site 10
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Gdynia、ポーランド
- Study site 04
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Katowice、ポーランド
- Study site 02
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Krakow、ポーランド
- Study site 03
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Krakow、ポーランド
- Study site 06
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Poznan、ポーランド
- Study site 09
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Warszawa、ポーランド
- Study site 01
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Warszawa、ポーランド
- Study Site 07
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Chihuahua、メキシコ
- Study site 02
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Distrito Federal、メキシコ
- Study site 03
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Distrito Federal
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Mexico、Distrito Federal、メキシコ
- Study site 05
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Mexico、Distrito Federal、メキシコ
- Study Site 08
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Guanajuato
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Leon、Guanajuato、メキシコ
- Study site 06
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Kaunas、リトアニア
- Study site 01
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Vilnus、リトアニア
- Study site 02
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Kemerovo、ロシア連邦
- Study Site 08
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Kemerovo、ロシア連邦
- Study site 11
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Kursk、ロシア連邦
- Study site 04
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Moscow、ロシア連邦
- Study site 03
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Moscow、ロシア連邦
- Study Site 07
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Moscow、ロシア連邦
- Study site 10
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Omsk、ロシア連邦
- Study site 05
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Saratov、ロシア連邦
- Study site 09
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Smolensk、ロシア連邦
- Study site 06
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Tomsk、ロシア連邦
- Study site 01
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Yaroslavl、ロシア連邦
- Study site 02
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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:
- Subject demonstrates active RA according to the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA with functional class I-III for ≥6 months.
- Subject receives oral or parenteral MTX treatment for ≥12 weeks (overall), with an unchanged mode of application and stable MTX dose of ≥15 mg per week (or ≥12.5 mg per week in case of MTX intolerance), but no more than the highest locally approved dose for RA, for ≥8 weeks prior to baseline. The dose of MTX is expected to remain stable throughout the study and may be adjusted only for safety reasons. If applicable, the dose of folic acid must be unchanged for ≥8 weeks prior to baseline.
- Subject meets the following two criteria at both screening and baseline: - At least 6 swollen joints at 28-joint assessment. - At least 6 tender joints at 28-joint assessment.
- Subject has an erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) above the upper limit of normal (ULN) at screening. These tests may be repeated once during the screening period at the discretion of the investigator.
- Subject is ≥18 and ≤75 years of age.
- Subject has a body mass index ≥18 and ≤35 kg/m².
- Subject receives treatment with corticosteroids ≤10 mg prednisone equivalent, stable for at least 4 weeks prior to baseline and during the study, if applicable.
- Subject receives treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable for at least 2 weeks prior to baseline and during the study, if applicable.
- Female subjects of childbearing potential: has both a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
- Subject is judged to be in good general health as determined by the investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (within 3 months before screening date is acceptable), and 12-lead electrocardiogram (ECG).
- Subject has a cluster of differentiation 4 (CD4) cell count of > 400/µl at screening.
Exclusion Criteria:
- Subject has previous exposure to any systemic biologic therapy (e.g., etanercept, adalimumab, rituximab, abatacept, tocilizumab), to Janus kinase (JAK) or spleen tyrosine kinase (SYK) inhibitors, or to Tregalizumab. Previous treatment with an anti-TNF agent is allowed only, if all of the following criteria apply: - treatment was stopped for reasons other than lack of efficacy or adverse events (AEs) - treatment was stopped at least 12 weeks or five half-lives of the compound prior to baseline (whichever is longer), and - the treatment period did not exceed 6 weeks.
- Subject received treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) apart from MTX in the 12 weeks prior to baseline, and for DMARD leflunomide in the 24 weeks prior to baseline (except where specific leflunomide wash-out procedures were completed, following applicable guidelines).
- Subject has been treated with intra-articular or parenteral administration of corticosteroids in the 4 weeks prior to baseline. Inhaled corticosteroids for stable medical conditions are allowed.
- Subject has undergone joint surgery in the 12 weeks prior to baseline (at joints to be assessed within the study) or has undergone major surgery (e.g., abdominal surgery) in the 8 weeks prior to baseline.
- Subject has a history of acute inflammatory joint disease of an origin other than RA or subject has any other rheumatic disease other than RA (e.g., mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter's syndrome, fibromyalgia, systemic lupus erythematosus or any arthritis with onset prior to age 17 years). However, subjects may have secondary Sjögren's syndrome.
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:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Dose Level 1 Tregalizumab
25mg Tregalizumab s.c. weekly
|
humanized anti-CD4 mAb
他の名前:
|
実験的:Dose Level 2 Tregalizumab
100mg Tregalizumab s.c. weekly
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humanized anti-CD4 mAb
他の名前:
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実験的:Dose Level 3 Tregalizumab
200mg Tregalizumab s.c. weekly
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humanized anti-CD4 mAb
他の名前:
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プラセボコンパレーター:Placebo
Placebo s.c. weekly
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identical end formulation buffer
|
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 |
---|---|---|
The Proportion of Subjects Who Achieve an ACR20 at Week 12 Following Treatment With Tregalizumab + MTX Compared With Subjects Treated on Placebo + MTX
時間枠:Week 12
|
The primary efficacy variable was the proportion of subjects with an ACR20 response after 12 weeks of double-blind treatment with the study medication. The analysis of the primary endpoint was performed using observed cases (OC) on the FAS. |
Week 12
|
二次結果の測定
結果測定 |
時間枠 |
---|---|
Proportions of Subjects With an ACR 20 Response.
時間枠:Week 24
|
Week 24
|
Proportions of Subjects With an ACR 50 & 70 Response.
時間枠:Week 12 & Week 24
|
Week 12 & Week 24
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Proportions of Subjects With an Disease Activity Score DAS28 <2.6
時間枠:Week 12 & Week 24
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Week 12 & Week 24
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Proportions of Subjects With Low Disease Activity DAS28 ≤3.2
時間枠:Week 12 & Week 24
|
Week 12 & Week 24
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ACR Score
時間枠:up to 48 weeks
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up to 48 weeks
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Simple Disease Activity Index [SDAI] ≤11
時間枠:week 12 & 24
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week 12 & 24
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Clinical Disease Activity Index [CDAI] ≤10
時間枠:week 12 & 24
|
week 12 & 24
|
DAS28
時間枠:up to 48 weeks
|
up to 48 weeks
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EULAR Response
時間枠:up to 48 weeks
|
up to 48 weeks
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ACR Score Individual Components
時間枠:up to 48 weeks
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up to 48 weeks
|
DAS28 Score Individual Components
時間枠:up to 48 weeks
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up to 48 weeks
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Pharmacokinetics
時間枠:up to 48 weeks
|
AUC, Cmax, Tmax at baseline, and at Week (W) 2/Visit (V) 4, W4/V5, W8/V7, W12/V8, W24/V10, W3/V122, W48 (end of Treatment [EoT]/ early termination ET), and at follow-up (post EoT/post ET).
|
up to 48 weeks
|
Evaluation of Safety, Patient Reported Outcomes & Blood Tests.
時間枠:up to 48 weeks
|
up to 48 weeks
|
協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
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 (見積もり)
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
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。