A Multi-Site, Randomized, Placebo-Controlled, Double-Blind, Phase 2 Clinical Trial of EG-501 for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 131
- 试验地点
- 3
- 主要终点
- Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)
研究概览
简要总结
Neuropsychiatric systemic lupus erythematosus with cognitive impairment (NPSLE-CI) is a serious, disabling, and potentially life-threatening manifestation of SLE, affecting up to 80% of patients with cognitive impairments ("brain fog"), leading to substantial disability, approximately 2 times higher unemployment risk, reduced health-related quality of life (HRQoL), and mortality 2-14 times higher than the general population (standardized mortality ratio, SMR). No approved therapies exist for NPSLE cognitive dysfunction, representing a high-priority unmet need for this FDA-recognized serious condition with major functional and psychosocial burden. The objective of this study is to evaluate the safety, tolerability and efficacy of EG-501 in a precise patient subset with NPSLE. Participants will complete a full 14-week clinical trial, receiving either EG-501 or a placebo.
详细描述
Protocol EG-501-2.1 is a Phase 2, multi-site, randomized, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of EG-501 for the treatment of cognitive impairment in systemic lupus erythematosus (SLE). The primary objective was to assess whether a 12-week EG-501 regimen produces a statistically and clinically significant improvement in the Total Scale Index score of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS®), compared with matched placebo, in a precisely defined SLE population with objective cognitive impairment. Fifty-six (56) patients were randomized treatment, 30 to placebo group and 26 to EG-501 group. All but three patients were female. Median age was 44.0 and 45.5 for placebo and EG-501 groups, respectively. With patients recruited only from the US, racial distribution was about 2/3 white, 1/3 black, with ethnicity reflecting largely non-Hispanic demographics.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Physician diagnosis of SLE;
- •Report NPSLE symptoms on the screening survey recommended by EULAR guideline but limited to a subset of the psychiatric manifestations questions and using a cut-off score of at least 5, with a minimum of 2.5 being scored on section 1;
- •Score ≤ 85 on the RBANS total index (≤ 1 SD below the normative mean of 100)
排除标准
- •Male and female subjects <18 or >69 years;
- •Change in medication that may affect mood or cognition including prednisone, antidepressant medications, analgesics including opioids, or stimulants within the last 4 weeks;
- •Metabolic derangement defined as liver function tests >3x upper limit of normal, or severe renal disease defined as calculated creatinine clearance<30 mL;
- •Severe psychiatric disease including schizophrenia, psychosis, suicidal depression, or substance abuse disorder;
- •Other factors which in the opinion of the investigator could potentially impact the study outcomes (e.g., underlying disease, medications, history)* or prevent the participant from completing the protocol (poor compliance or unpredictable schedule);
研究组 & 干预措施
Drug: Placebo
At randomization, subjects will receive one matching placebo capsule twice per day for one week. One matching placebo capsule twice per day will be taken for the next week (Week 2), then one matching placebo capsule in the morning and two capsules at night for one week (Week 3), and finally two capsules twice per day for three weeks (Weeks 4-6). Maximum tolerated number of capsules will be determined at this time and this dose will be continued for an additional six weeks.
干预措施: Placebo (Drug)
Drug: EG-501
EG-501/ EG-MNTP-01, Strength: 5 mg or 10 mg, oral capsules
At randomization, subjects will receive 5 mg twice per day for one week. Dose will be escalated to 10 mg twice per day for one week, then 10 mg in the morning and 20 mg at night for one week, and finally 20 mg twice per day for three weeks. Maximum tolerated will be determined at this time and this dose will be continued for an additional six weeks.
干预措施: EG-501 (Drug)
结局指标
主要结局
Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)
时间窗: 12 weeks
RBANS is a widely used psychiatric tool that objectively measures cognitive impairment. It is comprised of 12 subtests and takes approximately 30 minutes. For scoring, the RBANS index scores are converted to classifications including Very Superior (130 and above), Superior (120-129), High Average (110-119), Average (90-109), Low Average (80-89), Borderline (70-79), and Extremely Low (69 and below). A score of Extremely Low equates to severe cognitive impairment. The primary outcome measure will be analyzed using ANCOVA controlling for EG-501 or placebo, baseline RBANS, sex, age, and NMDAR status.
次要结局
- RBANS Subscales(12 weeks)
- Incidence of Treatment-Emergent Adverse Events(12 weeks)
- Polysymptomatic Distress Scale(12 weeks)
- Beck Depression Inventory(12 weeks)
- Hospital Anxiety and Depression Scale(12 weeks)
- Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K(12 weeks)
- Patient Global Impression of Change (PGIC)(12 weeks, Endpoint (Visit 4))