A Phase 2, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects With Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 626
- 试验地点
- 79
- 主要终点
- Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of MEDI-546 compared to placebo in subjects with chronic, moderately-to-severely active systemic lupus erythematosus (SLE) with an inadequate response to standard of care treatment for SLE.
详细描述
This is a Phase 2, multinational, multicenter, randomized, double-blind, placebo controlled, parallel-group study to evaluate the efficacy and safety of 2 intravenous (IV) treatment regimens in adult participants with chronic, moderately-to-severely active SLE with an inadequate response to SOC SLE. The investigational product (anifrolumab or placebo) will be administered as a fixed dose every 4 weeks (28 days) for a total of 13 doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fulfills at least 4 of the 11 American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) including a positive antinuclear antibody (ANA) greater than or equal to 1:80 or elevated anti-double-stranded DNA or anti-Smith antibody at screening
- •Pediatric or adult SLE with chronic disease activity for greater than or equal to 24 weeks
- •Weight greater than or equal to 40 kg
- •Currently receiving stable dose of oral prednisone (or equivalent) less than or equal to 40 mg/day and/or antimalarials/immunosuppressives
- •Active moderate to severe SLE disease based on SLE disease activity score (SLEDAI) and British Isles Lupus Assessment Group Index (BILAG) and Physicians Global Assessment
- •No evidence of cervical malignancy on Pap smear within 2 years of randomization
- •Female participants must be willing to avoid pregnancy
- •Negative tuberculosis (TB) test or newly positive TB test due to latent TB for which treatment must be initiated at or before randomization.
排除标准
- •Active severe SLE-driven renal disease or unstable renal disease prior to screening
- •Active severe or unstable neuropsychiatric SLE
- •Clinically significant active infection including ongoing and chronic infections
- •History of human immunodeficiency virus (HIV)
- •Confirmed Positive tests for hepatitis B or positive test for hepatitis C
- •History of severe herpes infection such as herpes encephalitis, ophthalmic herpes, disseminated herpes
- •Live or attenuated vaccine within 4 weeks prior to screening
- •Participants with significant hematologic abnormalities.
结局指标
主要结局
Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169
时间窗: Day 169
Type I IFN signature in whole blood assessed by using a 4-gene diagnostic test. The blood samples collected were to be used to prospectively identify participants as IFN test-high or test-low. The results of this test were used to stratify participants. An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of \>= 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 mg/day and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model.
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169
时间窗: Day 169
An SRI (4) responder defined as a participant who had 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to (\>=) 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index 'A' organ system score and no more than one new or worsening BILAG-2004 Index 'B' organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model.
次要结局
- Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events(Day 1 (Baseline) to Day 422 (End of Study))
- Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365(Day 365)
- Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365(Pre-infusion and 15 minutes post-infusion on Day 169 and 365)
- Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)(Day 1 (Baseline) to Day 422 (End of Study))
- Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365(Day 365)
- Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)(Day 1 (Baseline) to Day 422 (End of Study))
- Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365(Pre-infusion and 15 minutes post-infusion on Day 29, 169 and 365)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Day 1 (Baseline) to Day 422 (End of Study))
- Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature(Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period))
- Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)(Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period))
- Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337(Pre-infusion and 15 minutes post-infusion on Day 1, 169 and 337)
- Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab(Pre-infusion and 15 minutes post-infusion on Day 169 and 337)