EG-501 for Cognitive Impairment in Neuropsychiatric SLE (NPSLE): Efficacy and Safety Study

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

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.

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.

Key Inclusion Criteria:

1. Physician diagnosis of SLE;
2. 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;
3. Score ≤ 85 on the RBANS total index (≤ 1 SD below the normative mean of 100)

Key Exclusion Criteria:

1. Male and female subjects <18 or >69 years;
2. Change in medication that may affect mood or cognition including prednisone, antidepressant medications, analgesics including opioids, or stimulants within the last 4 weeks;
3. Metabolic derangement defined as liver function tests >3x upper limit of normal, or severe renal disease defined as calculated creatinine clearance<30 mL;
4. Severe psychiatric disease including schizophrenia, psychosis, suicidal depression, or substance abuse disorder;
5. 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);