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临床试验/NCT05279417
NCT05279417已完成2 期

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 Methotrexate (MTX) Versus Placebo Plus MTX in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone

Aclaris Therapeutics, Inc.51 个研究点 分布在 4 个国家实际入组 251 人开始时间: 2022年2月1日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
入组人数
251
试验地点
51
主要终点
Percentage of Participants Achieving ACR20 at Week 12
研究概览研究设计入排标准研究组 & 干预措施方案终点试验结果研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
干预性
分配方式
随机
干预模型
平行分组
主要目的
治疗
盲法
四盲 (受试者、医护人员、研究者、结局评估者)

入排标准

年龄范围
18 Years 至 75 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • 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.

排除标准

  • 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.

研究组 & 干预措施

ATI-450 20 mg BID plus Methotrexate

Experimental

ATI-450 20 mg oral tablet twice daily (BID) with a stable weekly dose of methotrexate for 12 weeks

干预措施: ATI-450 20 mg oral tablet BID (Drug)

ATI-450 50 mg BID plus Methotrexate

Experimental

ATI-450 50 mg oral tablet BID with a stable weekly dose of methotrexate for 12 weeks

干预措施: ATI-450 50 mg oral tablet BID (Drug)

Placebo plus Methotrexate

Placebo Comparator

Placebo oral tablet BID with a stable weekly dose of methotrexate for 12 weeks

干预措施: Placebo oral tablet (Drug)

ATI-450 20 mg BID plus Methotrexate

Experimental

ATI-450 20 mg oral tablet twice daily (BID) with a stable weekly dose of methotrexate for 12 weeks

干预措施: Methotrexate (Drug)

ATI-450 50 mg BID plus Methotrexate

Experimental

ATI-450 50 mg oral tablet BID with a stable weekly dose of methotrexate for 12 weeks

干预措施: Methotrexate (Drug)

Placebo plus Methotrexate

Placebo Comparator

Placebo oral tablet BID with a stable weekly dose of methotrexate for 12 weeks

干预措施: Methotrexate (Drug)

方案终点

主要结局

Percentage of Participants Achieving ACR20 at Week 12

时间窗: Week 12

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.

Proportion of patients achieving ACR20 at Week 12

时间窗: Baseline to Week 12

次要结局

  • Percentage of Participants Achieving ACR50 at Week 12(Week 12)
  • Percentage of Participants Achieving ACR70 at Week 12(Week 12)
  • Change From Baseline in DAS28-CRP at Week 12(Baseline, Week 12)
  • Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12(Week 12)
  • Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12(Week 12)
  • Change From Baseline in HAQ-DI Score at Week12(Baseline, Week 12)
  • Change From Baseline in CDAI Score at Week 12(Baseline, Week 12)
  • Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8)(Week 12)
  • Percent Change From Baseline in hsCRP Level at Week 12(Baseline, Week 12)
  • Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12(Baseline, Week 12)
  • Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12(Baseline, Week 12)
  • ATI-450 and Metabolite (CDD-2164) Concentrations(2 hours postdose on Days 1, 8, and 85)
  • Proportion of patients achieving DAS28-CRP remission (score < 2.6) over time(Up to 12 Weeks)
  • Proportion of patients achieving ACR50/70 at Week 12(Baseline to Week 12)
  • Proportion of patients achieving ACR20/50/70 over time(Up to 12 Weeks)
  • Mean change from baseline in DAS28-CRP over time(Up to 12 Weeks)
  • Proportion of patients achieving DAS28-CRP low disease activity (score ≤ 3.2) over time(Up to 12 Weeks)
  • Proportion of patients achieving CDAI remission (score ≤ 2.8) over time(Up to 12 Weeks)
  • Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) score over time(Up to 12 Weeks)
  • Incidence of adverse events (AEs), serious AEs (SAEs), laboratory value abnormalities, electrocardiogram (ECG) abnormalities, vital signs abnormalities(Baseline to Week 12)
  • Mean change from baseline in CDAI over time(Up to 12 Weeks)
  • Percent change from baseline in hsCRP level over time(Up to 30 days after 12 weeks of treatment)
  • Health Assessment Questionnaire-Disability Index (HAQ-DI) score over time(Up to 12 Weeks)
  • Short Form Health Survey version-2.0 (SF-36v2) score over time(Up to 12 Weeks)
  • Trough ATI-450 and metabolite (CDD-2164) concentrations at clinic visits (trough and 2-hour post dose will be collected).(Study Days 1, 8, and 85)

试验结果

结果已于 2026-09-28 在 ClinicalTrials.gov 公示。 在 ClinicalTrials.gov 查看

受试者流程

入组 251 人 · 完成 202 人

主要终点

Percentage of Participants Achieving ACR20 at Week 12

percentage of participants · 95% Confidence Interval · 时间窗: Week 12

Percentage of Participants Achieving ACR20 at Week 12
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=84）
42.2 (31.5–52.9)34.7 (24.2–44.9)46.5 (35.7–57.2)

ITT population: All participants who were randomized.

Difference in Model Estimate -4.22 · 95% 置信区间 -19.38–10.95 · p = 0.585 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or janus kinase (JAK) RA treatment.

Difference in Model Estimate -11.78 · 95% 置信区间 -26.63–3.07 · p = 0.120 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

其他终点（12）

Percentage of Participants Achieving ACR50 at Week 12

percentage of participants · 95% Confidence Interval · 时间窗: Week 12

Percentage of Participants Achieving ACR50 at Week 12
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=84）
20.9 (12.1–29.7)20.7 (12.0–29.4)27.7 (18.1–37.3)

ITT population: All participants who were randomized.

Difference in Model Estimate -6.80 · 95% 置信区间 -19.84–6.23 · p = 0.305 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Difference in Model Estimate -7.05 · 95% 置信区间 -20.02–5.93 · p = 0.286 · Regression, Logistic

Significance level = 0.05.

Percentage of Participants Achieving ACR70 at Week 12

percentage of participants · 95% Confidence Interval · 时间窗: Week 12

Percentage of Participants Achieving ACR70 at Week 12
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=84）
8.9 (2.8–15.1)7.6 (1.9–13.3)14.7 (7.1–22.3)

ITT population: All participants who were randomized.

Difference in Model Estimate -5.77 · 95% 置信区间 -15.53–3.99 · p = 0.246 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Difference in Model Estimate -7.05 · 95% 置信区间 -16.53–2.43 · p = 0.144 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Change From Baseline in DAS28-CRP at Week 12

units on a scale · Standard Error · 时间窗: Baseline, Week 12

Change From Baseline in DAS28-CRP at Week 12
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=84）
-1.66 (0.170)-1.64 (0.167)-1.60 (0.162)

ITT population: All participants who were randomized.

Difference in LS Means -0.06 · 95% 置信区间 -0.53–0.40 · p = 0.797 · MMRM

Significance level = 0.05.

Difference in LS Means -0.04 · 95% 置信区间 -0.49–0.41 · p = 0.870 · MMRM

Significance level = 0.05.

Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12

percentage of participants · 95% Confidence Interval · 时间窗: Week 12

Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=84）
19.8 (11.1–28.4)14.8 (7.2–22.4)21.9 (13.0–30.8)

ITT population: All participants who were randomized.

Difference in Model Estimate -2.12 · 95% 置信区间 -14.49–10.25 · p = 0.736 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Difference in Model Estimate -7.06 · 95% 置信区间 -18.77–4.65 · p = 0.236 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12

percentage of participants · 95% Confidence Interval · 时间窗: Week 12

Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=84）
24.1 (14.8–33.4)19.1 (10.7–27.6)29.8 (19.9–39.7)

ITT population: All participants who were randomized.

Difference in Model Estimate -5.63 · 95% 置信区间 -19.19–7.93 · p = 0.414 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Difference in Model Estimate -10.64 · 95% 置信区间 -23.65–2.37 · p = 0.108 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Change From Baseline in HAQ-DI Score at Week12

units on a scale · Standard Error · 时间窗: Baseline, Week 12

Change From Baseline in HAQ-DI Score at Week12
ATI-450 20 mg Plus MTX （n=76）ATI-450 50 mg Plus MTX （n=79）Placebo Plus MTX （n=81）
-0.24 (0.072)-0.33 (0.067)-0.37 (0.063)

ITT population: All participants who were randomized. Here, Overall number of participants analyzed' = participants evaluable for this endpoint.

Difference in LS Means 0.14 · 95% 置信区间 -0.04–0.31 · p = 0.136 · MMRM

LS Mean Difference 0.04 · 95% 置信区间 -0.13–0.21 · p = 0.622 · MMRM

Significance level = 0.05.

Change From Baseline in CDAI Score at Week 12

units on a scale · Standard Error · 时间窗: Baseline, Week 12

Change From Baseline in CDAI Score at Week 12
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=83）
-18.39 (1.595)-17.79 (1.669)-17.89 (1.524)

ITT population: All participants who were randomized. Here, Overall number of participants analyzed' = participants evaluable for this endpoint.

Difference in LS Means -0.50 · 95% 置信区间 -4.66–3.65 · p = 0.812 · MMRM

Significance level = 0.05.

Difference in LS Means 0.10 · 95% 置信区间 -4.10–4.30 · p = 0.963 · MMRM

Significance level = 0.05.

Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8)

percentage of participants · 95% Confidence Interval · 时间窗: Week 12

Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8)
ATI-450 20 mg Plus MTX （n=83）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=84）
6.6 (1.3–12.0)6.6 (1.2–11.9)7.7 (2.0–13.5)

ITT population: All participants who were randomized.

Difference in Model Estimate -1.11 · 95% 置信区间 -8.94–6.72 · p = 0.780 · Regression, Logistic

Significance level = 0.05.

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Difference in Model Estimate -1.18 · 95% 置信区间 -8.97–6.60 · p = 0.765 · Regression, Logistic

Firth's penalized likelihood logistic regression model with fixed effects for treatment, and use of prior biologic or JAK RA treatment.

Percent Change From Baseline in hsCRP Level at Week 12

percent change · Full Range · 时间窗: Baseline, Week 12

Percent Change From Baseline in hsCRP Level at Week 12
ATI-450 20 mg Plus MTX （n=67）ATI-450 50 mg Plus MTX （n=59）Placebo Plus MTX （n=76）
-28.274 (-89.766–1121.053)-22.779 (-86.392–528.571)1.546 (-93.280–838.047)

ITT population: All participants who were randomized. Here, 'Overall number of participants analyzed' = participants evaluable for this endpoint

Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12

units on a scale · Standard Error · 时间窗: Baseline, Week 12

Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12
ATI-450 20 mg Plus MTX （n=78）ATI-450 50 mg Plus MTX （n=80）Placebo Plus MTX （n=81）
6.48 (1.025)7.08 (1.057)7.01 (0.935)

ITT population: All participants who were randomized. Here, 'Overall number of participants analyzed' = participants evaluable for this endpoint.

LS Mean Difference -0.53 · 95% 置信区间 -3.14–2.07 · p = 0.687 · MMRM

Significance level = 0.05.

LS Mean Difference 0.07 · 95% 置信区间 -2.52–2.66 · p = 0.958 · MMRM

Significance level = 0.05.

Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12

units on a scale · Standard Error · 时间窗: Baseline, Week 12

Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12
ATI-450 20 mg Plus MTX （n=76）ATI-450 50 mg Plus MTX （n=78）Placebo Plus MTX （n=81）
4.21 (1.296)6.93 (1.313)6.53 (1.168)

ITT population: All participants who were randomized. Here, 'Number analyzed' = participants evaluable for specified category.

LS Mean Difference -2.32 · 95% 置信区间 -5.66–1.03 · p = 0.174 · MMRM

Significance level = 0.05.

LS Mean Difference 0.40 · 95% 置信区间 -3.01–3.81 · p = 0.816 · MMRM

Significance level = 0.05.

ATI-450 and Metabolite (CDD-2164) Concentrations

ng/milliliters (mL) · Standard Deviation · 时间窗: 2 hours postdose on Days 1, 8, and 85

ATI-450 and Metabolite (CDD-2164) Concentrations
分类ATI-450 20 mg Plus MTX （n=81）ATI-450 50 mg Plus MTX （n=84）Placebo Plus MTX （n=82）
ATI-450 Day 179.289 (46.0493)177.627 (120.9491)0.398 (0.7727)
ATI-450 Day 8104.032 (41.8903)245.377 (113.5619)0.272 (0.1887)
ATI-450 Day 8594.615 (58.6913)244.670 (127.9654)0.303 (0.3185)
CDD-2164 Day 130.609 (18.8977)66.602 (47.0467)0.407 (0.9181)
CDD-2164 Day 836.375 (15.6280)89.692 (48.0216)0.261 (0.0890)
CDD-2164 Day 8533.219 (21.5870)89.196 (50.6267)0.285 (0.2916)

Pharmacokinetic (PK) population: All randomized participants who took at least 1 dose of study drug and had at least 1 evaluable PK measurement. Overall number of participants analyzed' = participants evaluable for this endpoint and 'Number analyzed' = participants evaluable for specified timepoint.

安全性

安全性
组别严重不良事件死亡
ATI-450 20 mg Plus MTX0 / 820 / 83
ATI-450 50 mg Plus MTX3 / 850 / 84
Placebo Plus MTX1 / 830 / 84
最常见的严重不良事件（人数）
最常见的严重不良事件（人数）
事件ATI-450 20 mg Plus MTXATI-450 50 mg Plus MTXPlacebo Plus MTX
Hepatic cirrhosis0 / 821 / 850 / 83
Gastrointestinal bacterial infection0 / 821 / 850 / 83
Pyelonephritis0 / 821 / 850 / 83
Ultrasound ovary abnormal0 / 821 / 850 / 83
Rheumatoid arthritis0 / 821 / 851 / 83

数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。

研究者

申办方类型
企业
责任方
申办方

研究点 (51)

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标识符

NCT 编号
NCT05279417
其他研究编号
ATI-450-RA-202, 2021-002860-31

日期

首次提交
(4年前)
首次发布
(4年前)
主要完成日期
(3年前)
研究完成日期
(2年前)
最近核实
(29天前)
最近更新
(前天)

监管与共享

FDA 监管药物
是
FDA 监管器械
否
是否有结果
是

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