NCT07515014招募中2 期
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose Response Study to Evaluate the Efficacy and Safety of E6742 in Subjects With Systemic Lupus Erythematosus
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 256
- 试验地点
- 64
- 主要终点
- Percentage of Participants who Achieve a BICLA Response with Low Dose of OCS (Prednisone or Equivalent) at Week 24
研究概览
简要总结
The main purpose of the study is to demonstrate the efficacy based on dose response of E6742 compared with placebo as defined by the proportion of participants achieving a response using the British Isles Lupus Assessment Group (BILAG) based Composite Lupus Assessment (BICLA) with a low dose of oral corticosteroids (OCS) (prednisone or equivalent) at Week 24 in participants with systemic lupus erythematosus (SLE).
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
- Double (Participant, Investigator)
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
- •Male or female adult, age >=18 years (the minimum age may be different from 18 years in certain countries based on regional requirements) and <=75 years at the time of informed consent
- •Diagnosed with SLE at least 6 months before the informed consent AND fulfill the 2019 EULAR/ACR classification criteria at Screening based on medical history
- •At least BILAG-2004 category A in >=1 organ system or BILAG-2004 category B in >=2 organ systems at screening
- •SLEDAI-2K score >=6 points at Screening AND Clinical SLEDAI-2K score >=4 points at Baseline
- •Receiving at least one of the following treatments for SLE (if more than 1 treatment is used, all medications must be within the dosage defined in the protocol):
- •OCS (<=30 mg/day, prednisone or equivalent): The dosing regimen should be stable for at least 4 weeks before the first dose of study drug.
- •Oral hydroxychloroquine (<=400 mg/day), quinacrine (<=200 mg/day): These medications should have been initiated or discontinued at least 12 weeks before the first dose of study drug, and the dosing regimen should remain stable for at least 8 weeks before the first dose.
- •Immunosuppressants: The following medications should have been initiated or discontinued at least 12 weeks before the first dose of study drug, and the dosing regimen should remain stable for at least 8 weeks before the first dose
- •Mycophenolate mofetil (<=3 g/day)
- •Mycophenolate sodium (<=2160 mg/day)
- •Azathioprine (<=200 mg/day)
- •6-mercaptopurine (<=100 mg/day)
- •Methotrexate (oral/subcutaneous/intramuscular) (<=25 mg/week)
- •Willing and able to provide written informed consent and comply with all aspects of the protocol
排除标准
- •Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG] test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- •Females of childbearing potential who:
- •Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
- •Total abstinence (if it is their preferred and usual lifestyle)
- •An intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- •A contraceptive implant
- •Combined estrogen and progestogen-containing hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception associated with inhibition of ovulation, such as desogestrel (oral, injectable). Participants using hormonal contraceptives must be on a stable dose of the same contraceptive product for at least 28 days before dosing, throughout the study, and for at least 28 days following study drug discontinuation.
- •Have a vasectomized partner with confirmed azoospermia
- •Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation.
- •Participants on an oral contraceptive must use an additional barrier method throughout the study and for 28 days after study drug discontinuation.
- •Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (ie, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation). No sperm donation is allowed during the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation.
- •Drug-induced lupus erythematosus
- •Active or unstable neuropsychiatric lupus (including but not limited to any condition defined by BILAG category A in neuropsychiatric organ system)
- •Systemic autoimmune diseases other than SLE (eg, rheumatoid arthritis, Crohn's disease, systemic sclerosis [SSc], multiple sclerosis, polymyositis/ dermatomyositis [PM/DM]) that may affect the assessment of SLE pathology at Screening. The participants with the following diseases may be included in the study
- •Sjögren's syndrome secondary to SLE
- •Antiphospholipid antibody syndrome (APS) secondary to SLE
- •Mixed Connective Tissue Disease (MCTD) not meeting diagnostic criteria for PM and SSc
- •Any clinically significant symptom or organ impairment found by chest X-ray, ophthalmic examination, vital signs, or ECG finding at Screening or Baseline, laboratory test at Screening that in the opinion of the investigator could affect the participants safety or interfere with the study assessments.
- •Laboratory test results meeting any of the following criteria at Screening:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper limit of normal (ULN)
- •Absolute neutrophil count (ANC) <1,000 /mcL
- •Platelet count <50,000 /mcL
- •Hemoglobin <8.0 g/dL
- •Renal impairment falling under any of the following criteria at Screening:
- •Urine protein/creatinine ratio >2.0 g/gCr
- •Estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <40 mL/min/1.73 m^2
- •Received vaccination within 2 weeks before the first dose of study drug (4 weeks before in case of live/ live attenuated vaccines)
- •Currently or previously receiving gene therapy for SLE (eg, CAR-T cell therapy)
- •Currently enrolled in another clinical study or used any investigational drug or device (including E6742) within 28 days (or 5× the half-life, whichever is longer) before obtaining informed consent
- •Any history of the following clinically significant infections:
- •Infections requiring hospitalization or intravenous antibiotics, or administration of antiviral drugs, within 4 weeks before the first dose of study drug
- •Active tuberculosis
- •Any findings indicating a history of tuberculosis on chest X-ray at Screening
- •Positive or repeated hold (indeterminate or intermediate) in tuberculosis test (Interferon-γ release assays) at Screening
- •A prolonged QTc interval calculated using Fridericia's formula (QTcF) greater than 450 millisecond (ms) according to central reading at Screening. If the QTcF machine read is greater than 440 ms on the first single 12-lead ECG, 2 additional 12-lead ECGs will be performed 1 minute apart and the mean of the 3 QTcF values will be used for evaluation.
- •A prolonged QTcF interval (mean QTcF >450 ms) as demonstrated by triplicated ECGs at Baseline. Has any risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QTcF interval (excluding hydroxychloroquine).
- •Hypersensitivity to the study drug, drug product chemical derivate or any of the excipients at Screening
- •Any history of or concomitant medical condition that in the opinion of the investigators would compromise the participants ability to safely complete the study
- •Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery which requires only local anesthesia and that can be undertaken as a day case without inpatient stay postoperatively need not result in exclusion if in the opinion of the investigator this operation does not interfere with study procedures and participant safety
- •Positive on test at Screening for human immunodeficiency virus (HIV)
- •Positive on test at Screening for hepatitis B virus (HBV) with a detectable (eg, hepatitis B virus surface [HBs] antigen reactive, HBs antibody, hepatitis B virus core [HBc] antibody, HBV deoxyribose nucleic acid (DNA)) or hepatitis C virus (HCV) with a detectable (eg, HCV ribonucleic acid (RNA) [qualitative], HCV antibody) viral load
- •Psychotic disorders or unstable recurrent affective disorders evident by use of antipsychotics within 2 years before Screening
- •History of drug or alcohol dependency or abuse within 2 years before Screening
- •History or concurrent of malignancy, lymphoma, leukemia, or lymphoproliferative disease (except for basal cell skin cancer, squamous cell skin cancer, and cervical cancer that have been cured by surgical operation)
- •Assessed to be inappropriate for clinical study by investigators
研究组 & 干预措施
E6742 Dose B
Experimental
干预措施: E6742 (Drug)
E6742 Dose A
Experimental
干预措施: E6742 (Drug)
Placebo
Placebo Comparator
干预措施: Placebo (Other)
E6742 Dose C
Experimental
干预措施: E6742 (Drug)
结局指标
主要结局
Percentage of Participants who Achieve a BICLA Response with Low Dose of OCS (Prednisone or Equivalent) at Week 24
时间窗: At Week 24
The BICLA is a composite index used to assess disease activity in SLE. A BICLA response is defined as reduction of all baseline BILAG-2004 A to B or C or D; and baseline BILAG-2004 B to C or D; no BILAG-2004 worsening in other organ systems, as defined by greater than or equal to (\>=1) new BILAG-2004 A or \>= 2 new BILAG-2004 B; no worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) as defined as an increase from baseline of greater than (\>) 0 points in SLEDAI-2K; no worsening from baseline in participants lupus disease activity defined by an increase \>=0.30 points on a 3-point Physician Global Assessment Visual Analogue Scale (PGA VAS); and no treatment failure.
次要结局
- Frequency and Percentage of Abnormal Findings in Chest X-rays(From baseline up to Week 48)
- Percentage of Participants with Low Dose of OCS (Prednisone or Equivalent) at Week 24(At Week 24)
- Percentage of Participants who Achieve an SLE Responder Index- 4 (SRI-4) Response with Low Dose of OCS (Prednisone or Equivalent) at Week 24(At Week 24)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent SAEs(From baseline up to 52 weeks)
- Number of Participants With Clinically Significant Changes in Laboratory Parameters(From baseline up to 52 weeks)
- Number of Participants With Clinically Significant Changes in Vital Signs(From baseline up to 52 weeks)
- Frequency and Percentage of Abnormal Findings in 12-lead Electrocardiogram (ECG) Parameters(From baseline up to 52 weeks)
- Frequency and Percentage of Abnormal Findings in Ophthalmic Examination(From baseline up to Week 48)
- Change From Baseline in SLEDAI-2K(Baseline, at Week 24)
- Change From Baseline in BILAG-2004(Baseline, at Week 24)
- Change From Baseline in PGA(Baseline, at Week 24)
- Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)(Baseline, at Week 24)
- Change From Baseline in Joint Count(Baseline, at Week 24)
- Change From Baseline in Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) Damage Index)(Baseline, at Week 24)
- Change From Baseline in Autoantibody(Baseline, at Week 24)
- Change From Baseline in Complements (C3 and C4)(Baseline, at Week 24)
- Change From Baseline in Lupus-Patient-Reported Outcomes (Lupus-PRO)(Baseline, at Week 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)(Baseline, at Week 24)
- Percentage of Participants who Achieve a BICLA Response(At Week 24)
- Percentage of Participants who Achieve a SLE Responder Index- X (SRI-X) Response(At Week 24)
- Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS)(At Week 24)
- Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) Remission(At Week 24)
- Duration in a LLDAS(Week 24)
- Duration in a DORIS Remission(Week 24)
- Time to First Response of BICLA(Week 24)
- Time to First Response of SRI-4(Week 24)
- Percentage of Participants with mild/Moderate, or Severe Flares Assessed by Hybrid SELENA-SLEDAI Flare Index(At Week 24)
- Percentage of Participants with Mild, Moderate, or Severe Flares Assessed by BILAG- 2004 Flare(At Week 24)
- Percentage of Participants who Achieve a CLASI-50 Response(At Week 24)
- Plasma concentrations of E6742(Up to 24 weeks)
研究者
研究点 (64)
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