Neuropsychiatric Systemic Lupus ErythematosusPhase 2NCT07281105
EG-501 for Cognitive Impairment in Neuropsychiatric SLE (NPSLE): Efficacy and Safety Study
A Phase 2 study testing EG-501 in people with Neuropsychiatric Systemic Lupus Erythematosus and Systemic Lupus Erythematosus (SLE), run by Evergreen Therapeutics, Inc. at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Neuropsychiatric Systemic Lupus Erythematosus, Systemic Lupus Erythematosus (SLE), Cognitive Impairment
- What is being tested?
- EG-501
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 131 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 Aug 2018to 12 Aug 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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);
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cleveland Clinic
Cleveland, Ohio, 44195
UT Health Houston
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Neuropsychiatric Systemic Lupus Erythematosus, Systemic Lupus Erythematosus (SLE), Cognitive Impairment
- Being tested
- Placebo, EG-501
- Medical subject headings
- Lupus Vasculitis, Central Nervous System, Lupus Erythematosus, Systemic, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
The placebo will match the study drug in appearance, dose, and frequency. It will not contain any active drug (EG-501).
EG-501Drug
Also called EG-MNTP-01
EG-501/ EG-MNTP-01 is an oral, low-affinity NMDA receptor antagonist.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: EG-501 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (7)
RBANS Subscales
Our primary outcome is the RBANS Total Index Score, which is the sum of several subscales/tests. For a secondary outcome, each subscale/test individually to see if there is a trend for any one test in particular will be recorded. The subscales are all scored the same (40 - 160) and include immediate memory, delayed memory, visuospatial/constructional, language, and attention.
Measured: 12 weeks
Incidence of Treatment-Emergent Adverse Events
The safety of EG-501 as measured by treatment-emergent adverse events will be determined.
Measured: 12 weeks
Polysymptomatic Distress Scale
The Polysymptomatic Distress (PSD) scale measures the effect of PSD over a range of pain-related clinical symptoms. The scale was derived from variables used in the 2010 American College of Rheumatology fibromyalgia criteria, modified for use in clinical research, and broadened to be applicable for patients not meeting fibromyalgia diagnostic criteria. The PSD score is calculated by summing two components, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS). The WPI is a count of painful nonarticular body regions, and the SSS is a symptom severity measure that includes fatigue, sleep, and cognitive problems.
Measured: 12 weeks
Beck Depression Inventory
The Beck Depression Inventory (BDI) is a 21-item, self-report inventory that measures depression symptoms and attitudes. It takes approximately 10 minutes to complete and requires a fifth to sixth grade reading level to adequately comprehend the questions.
Measured: 12 weeks
Hospital Anxiety and Depression Scale
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale and was developed to detect states of depression, anxiety, and emotional distress among patients who were being treated for a variety of clinical problems. The scale has a total of 14 items, with responses being scored on a scale of 0-3 (3 indicates higher symptom frequencies). Scores for each subscale (anxiety and depression) range from 0 to 21, categorized as follows: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.
Measured: 12 weeks
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K
SLEDAI-2K is an updated version of the SLEDAI which was originally developed in 1985 as a clinical index to assess lupus disease activity in the preceding 10 days. It is a cumulative and weighted index of 24 different clinical and laboratory variables/disease descriptors, comprising 9 organ systems. The Investigator will assess disease descriptors on the SLEDAI-2K collection sheet (e.g., arthritis, myositis, alopecia, rash, mucosal ulcers, etc.).
Measured: 12 weeks
Patient Global Impression of Change (PGIC)
Participants will answer the standard question, "Considering all the ways your health affects you, how are you doing since the beginning of your treatment?" Answers include very much worse, much worse, worse, unchanged, improved, much improved, and very much improved.
Measured: 12 weeks, Endpoint (Visit 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start23 Aug 2018
- Primary completion12 Aug 2025
- Study completion12 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuropsychiatric Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Stratified, randomized, double-blind, placebo-controlled, parallel group study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Evergreen Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Vanderbilt University Medical Center
- Responsible party
- Sponsor
- Investigators
- Leslie J. Crofford, M.D., Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07281105
- Sponsor's protocol ID
- EG-501-2.1
- Status last verified
- Dec 2025
- First submitted
- 2 Dec 2025
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07281105
- Acronym / sponsor ID
- EG-501-2.1
- Conditions
- Neuropsychiatric Systemic Lupus Erythematosus, Systemic Lupus Erythematosus (SLE), Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Evergreen Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Vanderbilt University Medical Center
- Study start
- 23 Aug 2018 (actual)
- Primary completion
- 12 Aug 2025 (actual)
- Study completion
- 12 Aug 2025 (actual)
- First posted
- 15 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Stratified, randomized, double-blind, placebo-controlled, parallel group study
| Arm | Type | Receives |
|---|---|---|
| Drug: Placebo | Placebo comparator | Drug: PlaceboAt 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: EG-501 | Experimental | Drug: EG-501EG-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. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboThe placebo will match the study drug in appearance, dose, and frequency. It will not contain any active drug (EG-501). | Drug | Drug: Placebo |
| EG-501Also: EG-MNTP-01EG-501/ EG-MNTP-01 is an oral, low-affinity NMDA receptor antagonist. | Drug | Drug: EG-501 |
Primary outcome
Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)
Time frame: 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.
7 secondary outcomes
RBANS Subscales
Time frame: 12 weeks
Incidence of Treatment-Emergent Adverse Events
Time frame: 12 weeks
Polysymptomatic Distress Scale
Time frame: 12 weeks
Beck Depression Inventory
Time frame: 12 weeks
Hospital Anxiety and Depression Scale
Time frame: 12 weeks
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K
Time frame: 12 weeks
Patient Global Impression of Change (PGIC)
Time frame: 12 weeks, Endpoint (Visit 4)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leslie J. Crofford, M.D. principal investigator
Vanderbilt University Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EG-501 in people with Neuropsychiatric Systemic Lupus Erythematosus and Systemic Lupus Erythematosus (SLE), run by Evergreen Therapeutics, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.