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

NCT07281105 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: EG-501-2.1
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Neuropsychiatric Systemic Lupus Erythematosus; Systemic Lupus Erythematosus (SLE); Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)

  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.

  12 weeks

Secondary Outcomes (7)

• 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

Study Arms (2)

Drug: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Drug: EG-501

EXPERIMENTAL

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.

Drug: EG-501

Interventions

Placebo DRUG

The placebo will match the study drug in appearance, dose, and frequency. It will not contain any active drug (EG-501).

Drug: Placebo

EG-501 DRUG

EG-501/ EG-MNTP-01 is an oral, low-affinity NMDA receptor antagonist.

Also known as: EG-MNTP-01

Drug: EG-501

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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);

Sponsors & Collaborators

• Evergreen Therapeutics, Inc.: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (3)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Health Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lupus Vasculitis, Central Nervous System; Lupus Erythematosus, Systemic; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Meningoencephalitis; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Encephalitis; Neuroinflammatory Diseases; Meningitis; Vascular Diseases; Cardiovascular Diseases; Vasculitis; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Leslie J. Crofford, M.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Stratified, randomized, double-blind, placebo-controlled, parallel group study

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: December 15, 2025
• Study Start: August 23, 2018
• Primary Completion: August 12, 2025
• Study Completion: August 12, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

US (3)