中等度から重度の活動性 RA 患者における ATI-450 Plus MTX とプラセボ Plus MTX の比較
ATI-450 Plus MTX とプラセボ Plus MTX の比較 (MTX 単独では不十分な反応を示した中等度から重度の活動性 RA 患者)
This study evaluates ATI-450 plus MTX versus placebo plus MTX in participants with moderate to severe active RA who have had an inadequate response to MTX alone.
調査の概要
状態
条件
詳細な説明
This is a Phase 2b, randomized, multicenter, double-blind, parallel group, placebo controlled, dose ranging study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of ATI-450 plus MTX versus placebo plus MTX in participants with moderate to severe active RA who have had an inadequate response to MTX alone.
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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California
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El Cajon、California、アメリカ、92020
- Aclaris Investigational Site
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Encino、California、アメリカ、91436
- Aclaris Investigational Site
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La Jolla、California、アメリカ、92093
- Aclaris Investigational Site
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Palm Desert、California、アメリカ、92260
- Aclaris Investigational Site
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Florida
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Tampa、Florida、アメリカ、33613
- Aclaris Investigational Site
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73103
- Aclaris Investigational Site
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Pennsylvania
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Duncansville、Pennsylvania、アメリカ、16635
- Aclaris Investigational Site
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Tennessee
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Jackson、Tennessee、アメリカ、38305
- Aclaris Investigational Site
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Texas
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Cypress、Texas、アメリカ、77429
- Aclaris Investigational Site
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Mesquite、Texas、アメリカ、75150
- Aclaris Investigational Site
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San Antonio、Texas、アメリカ、78229
- Aclaris Investigational Site
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Brno、チェコ、615 00
- Aclaris Investigational Site
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Hlučín、チェコ、748 01
- Aclaris Investigational Site
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Ostrava、チェコ、702 00
- Aclaris Investigational Site
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Pardubice、チェコ、530 02
- Aclaris Investigational Site
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Prague、チェコ、128 50
- Aclaris Investigational Site
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Prague、チェコ、140 00
- Aclaris Investigational Site
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Uherské Hradiště、チェコ、686 01
- Aclaris Investigational Site
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Pleven、ブルガリア、5800
- Aclaris Investigational Site
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Plovdiv、ブルガリア、4000
- Aclaris Investigational Site
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Plovdiv、ブルガリア、4001
- Aclaris Investigational Site
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Plovdiv、ブルガリア、4002
- Aclaris Investigational Site
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Plovdiv、ブルガリア、4004
- Aclaris Investigational Site
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Sofia、ブルガリア、1336
- Aclaris Investigational Site
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Sofia、ブルガリア、1431
- Aclaris Investigational Site
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Sofia、ブルガリア、1606
- Aclaris Investigational Site
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Varna、ブルガリア、9000
- Aclaris Investigational Site
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Bialystok、ポーランド、15-297
- Aclaris Investigational Site
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Bialystok、ポーランド、15-879
- Aclaris Investigational Site
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Dąbrówka、ポーランド、62-069
- Aclaris Investigational Site
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Krakow、ポーランド、30-363
- Aclaris Investigational Site
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Lublin、ポーランド、20-607
- Aclaris Investigational Site
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Nowa Sól、ポーランド、67-100
- Aclaris Investigational Site
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Poznan、ポーランド、60-218
- Aclaris Investigational Site
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Poznan、ポーランド、60-446
- Aclaris Investigational Site
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Poznan、ポーランド、61-397
- Aclaris Investigational Site
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Sochaczew、ポーランド、96-500
- Aclaris Investigational Site
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Torun、ポーランド、87-100
- Aclaris Investigational Site
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Warsaw、ポーランド、04-141
- Aclaris Investigational Site
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Wroclaw、ポーランド、52-442
- Aclaris Investigational Site
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Lesser Poland Voivodeship
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Krakow、Lesser Poland Voivodeship、ポーランド、30-002
- Aclaris Investigational Site
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Lubelski
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Tomaszów Lubelski、Lubelski、ポーランド、22-600
- Aclaris Investigational Site
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Lublin Voivodeship
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Lublin、Lublin Voivodeship、ポーランド、20-362
- Aclaris Investigational Site
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Masovian Voivodeship
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Nadarzyn、Masovian Voivodeship、ポーランド、05-830
- Aclaris Investigational Site
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Mzowieckie
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Grodzisk Mazowiecki、Mzowieckie、ポーランド、05-825
- Aclaris Investigational Site
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Podlaskie Voivodeship
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Bialystok、Podlaskie Voivodeship、ポーランド、15-351
- Aclaris Investigational Site
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Silesian Voivodeship
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Katowice、Silesian Voivodeship、ポーランド、40-282
- Aclaris Investigational Site
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Warm.Maz.
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Elblag、Warm.Maz.、ポーランド、82-300
- Aclaris Investigational Site
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Warmińsko-Mazurskien
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Olsztyn、Warmińsko-Mazurskien、ポーランド、10-117
- Aclaris Investigational Site
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Wielkopolska
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Poznan、Wielkopolska、ポーランド、61-113
- Aclaris Investigational Site
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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:
- Able to comprehend and be willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved participant ICF prior to administration of any study-related procedures.
- Diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria.
- Have active moderate to severe RA at Screening.
- A minimum of 12 weeks on MTX with a stable MTX dose.
Exclusion Criteria:
- Current acute or chronic immunoinflammatory disease other than RA which may impact the course or assessment of RA.
- Uncontrolled non-immunoinflammatory disease that may place the participant at increased risk during the study or impact the interpretation of results (eg, previous malignancy, recurrent infection, previous venous thromboembolism).
- Participant has experience with > 2 biologics, > 1 JAK inhibitor, or a combination of 1 biologic experience and 1 JAK inhibitor.
- Currently receiving corticosteroids at doses > 10 mg/day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of screening.
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 |
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実験的：ATI-450 20 mg BID plus Methotrexate
ATI-450 20 mg oral tablet twice daily (BID) with a stable weekly dose of methotrexate for 12 weeks |
15 mg to 25 mg weekly Oral, small molecule MK2 inhibitor
他の名前：
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実験的：ATI-450 50 mg BID plus Methotrexate
ATI-450 50 mg oral tablet BID with a stable weekly dose of methotrexate for 12 weeks |
15 mg to 25 mg weekly Oral, small molecule MK2 inhibitor
他の名前：
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プラセボコンパレーター：Placebo plus Methotrexate
Placebo oral tablet BID with a stable weekly dose of methotrexate for 12 weeks |
15 mg to 25 mg weekly Placebo tablet manufactured to match ATI-450 in appearance |
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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Percentage of Participants Achieving ACR20 at Week 12
時間枠：Week 12
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Participants achieving American College of Rheumatology (ACR) 20 (responders) were defined as having ≥20% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥20% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician's Global Assessment of Disease Activity (VAS), and acute phase reactant as measured by hsCRP. Model-based estimates and 95% confidence intervals (CIs) were produced. |
Week 12
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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 |
|---|---|---|
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ATI-450および代謝物（CDD-2164）濃度
時間枠：投与後2時間、1日目、8日目、および85日目
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投与後2時間、1日目、8日目、および85日目
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Percentage of Participants Achieving ACR50 at Week 12
時間枠：Week 12
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Participant achieving ACR50 (responders) were defined as having ≥50% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥50% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced. |
Week 12
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Percentage of Participants Achieving ACR70 at Week 12
時間枠：Week 12
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Participants achieving ACR70 (responders) were defined as having ≥70% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥70% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced. |
Week 12
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Change From Baseline in DAS28-CRP at Week 12
時間枠：Baseline, Week 12
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The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP was used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where <2.6 is considered remission, ≥2.6 to <3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and >5.1 is considered high/severe disease activity. The least square (LS) mean change from baseline in DAS28-CRP at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model. |
Baseline, Week 12
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Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12
時間枠：Week 12
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The Disease Activity Score using 28 Joint Count-C-reactive protein (DAS28-CRP) consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where <2.6 is considered remission, ≥2.6 to <3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and >5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced. |
Week 12
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Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12
時間枠：Week 12
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The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where <2.6 is considered remission, ≥2.6 to <3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and >5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced. |
Week 12
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Change From Baseline in HAQ-DI Score at Week12
時間枠：Baseline, Week 12
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The HAQ-DI (standard disability method calculation) was utilized to assess the participant's physical function or disability according to the participant. The HAQ-DI is a 20-item, validated questionnaire used to assess the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities [errands and chores]). Responses in each functional area are scored from 0 (no difficulty) to 3 (inability to perform a ask in that area). Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3. A lower score demonstrated less disability. LS mean change from baseline in HAQ-DI score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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Change From Baseline in CDAI Score at Week 12
時間枠：Baseline, Week 12
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The Clinical Disease Activity Index (CDAI) was the sum of 4 outcome parameters:
Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, >2.8 to ≤10 was considered low/minimal disease activity, >10 to ≤22 was considered moderate disease activity, and >22.0 was considered high/severe disease activity. LS mean change from baseline in CDAI score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8)
時間枠：Week 12
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The CDAI was the sum of 4 outcome parameters:
Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, >2.8 to ≤10 was considered low/minimal disease activity, >10 to ≤22 was considered moderate disease activity, and >22.0 was considered high/severe disease activity. Model-based estimates and 95% CIs were produced. |
Week 12
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Percent Change From Baseline in hsCRP Level at Week 12
時間枠：Baseline, Week 12
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Blood samples were evaluated to measure levels of hsCRP. |
Baseline, Week 12
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Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12
時間枠：Baseline, Week 12
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The PCS is composed of 4 scales of the Short Form-36 Health Status Survey Questionnaire (SF-36) version 2 assessing physical function, role limitations caused by physical problems, bodily pain, and general health. The range of the SF-36 PCS is between 0 and 100, where higher scores represent better physical functioning. A 2.5 to 5-point change from baseline is established as the minimum clinically-important difference for the PCS in RA participants. LS mean change from baseline in SF-36 PCS score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12
時間枠：Baseline, Week 12
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The FACIT-Fatigue is a 13-item questionnaire that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a 4 point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is from 0 to 52. The higher the score, the lower the fatigue level. LS mean change from baseline in FACIT-Fatigue score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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協力者と研究者
捜査官
- スタディディレクター：Ajay Aggarwal、Aclaris Therapeutics, Inc.
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
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。