A Study in Participants With Anti-NMDAR Encephalitis and Anti-NMDAR Autoantibody-Associated Psychiatric Disease

NCT07093333 | Not Yet Recruiting Phase 2

• 1 other identifier: ART5803-201
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the safety, tolerability, preliminary efficacy and pharmacokinetics (PK) of ART5803 in adult participants with a confirmed diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (ANRE) or anti-NMDAR autoantibody-associated psychiatric disease

Conditions

Anti-N-methyl-D-aspartate Receptor (NMDAR) Encephalitis (ANRE); Autoimmune Encephalitis; Anti-N-methyl-D-aspartate Receptor (NMDAR) Antibody-associated Psychiatric Disease

Keywords

Anti-N-methyl-D-aspartate receptor (NMDAR); Encephalitis; Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis

Outcome Measures

Primary Outcomes (14)

• To assess the safety and tolerability of ART5803

  Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)

  26 weeks

• To assess the safety and tolerability of ART5803

  Clinically significant changes in physical examination findings.

  26 weeks

• To assess the safety and tolerability of ART5803

  Clinically significant changes in neurological examination findings

  26 weeks

• To assess the safety and tolerability of ART5803

  Vital signs - Systolic and diastolic blood pressure

  26 weeks

• To assess the safety and tolerability of ART5803

  Vital signs- Pulse rate

  26 weeks

• To assess the safety and tolerability of ART5803

  Vital signs- Body temperature

  26 weeks

• To assess the safety and tolerability of ART5803

  Vital signs- Respiratory rate

  26 weeks

• To assess the safety and tolerability of ART5803

  Clinical laboratory outcomes - Serum anti-ART5803 binding antibodies (ADA)

  26 weeks

• To assess the safety and tolerability of ART5803

  Concomitant medications

  26 weeks

• To assess the safety and tolerability of ART5803

  Change in suicidal tendency as measured by the incidence of positive responses (Yes) to Item 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) from baseline (Score range: 0-5 per item. Higher score indicated better symptoms)

  26 weeks

• To assess the safety and tolerability of ART5803

  Presence of anti-drug antibodies (ADAs)

  26 weeks

• To assess the safety and tolerability of ART5803

  Clinical laboratory outcomes - Hematology

  26 weeks

• To assess the safety and tolerability of ART5803

  Clinical laboratory outcomes - Serum Chemistry

  26 weeks

• To assess the safety and tolerability of ART5803

  12-lead Electrocardiogram (ECG) findings - QRS interval \>120 ms

  26 weeks

Secondary Outcomes (35)

• To assess the effects of ART5803 on Patient Reported Outcomes (PROs)

  26 weeks

• To assess the effects of ART5803 on Patient Reported Outcomes (PROs)

  26 weeks

• To assess the effects of ART5803 on Patient Reported Outcomes (PROs)

  26 weeks

• To assess the effects of ART5803 on Patient Reported Outcomes (PROs)

  26 weeks

• To assess the effects of ART5803 on neuropsychological assessments

  26 weeks

Other Outcomes (2)

• To assess the changes in cognition following ART5803 administration

  11 weeks

• To assess the change in use of rescue medications following ART5803 administration

  11 weeks

Study Arms (4)

Cohort A: Adult patients with chronic ANRE

EXPERIMENTAL

Drug: ART5803

Cohort B: Adult patients with subacute ANRE

EXPERIMENTAL

Drug: ART5803

Cohort C: Adult patients with acute ANRE

EXPERIMENTAL

Drug: ART5803

Cohort D: Adult patients with anti-NMDAR autoantibody-associated psychiatric disease

EXPERIMENTAL

Drug: ART5803-Cohort D

Interventions

ART5803 DRUG

A monovalent (one-armed) antibody, that binds to the NTD of the NMDAR NR1 subunit without causing NMDAR inhibition, activation, or receptor internalization, while simultaneously blocking the ability of the pathogenic anti-NMDAR autoantibodies to bind to the receptor. 1. Sentinel participants: 30 mg/kg 2. Subsequent participants: up to 60 mg/kg 3. Schedule: Q1W for 4 doses then Q2W for 4 doses

Cohort A: Adult patients with chronic ANRE; Cohort B: Adult patients with subacute ANRE; Cohort C: Adult patients with acute ANRE

ART5803-Cohort D DRUG

A monovalent (one-armed) antibody, that binds to the NTD of the NMDAR NR1 subunit without causing NMDAR inhibition, activation, or receptor internalization, while simultaneously blocking the ability of the pathogenic anti-NMDAR autoantibodies to bind to the receptor. Participants receive ART5803 by intravenous infusion once a week for 4 weeks, then every 2 weeks for 8 weeks, for a total of 8 doses. Sentinel participants receive 30 mg per kg. Additional participants may receive up to 60 mg per kg based on Safety Review Committee guidance.

Cohort D: Adult patients with anti-NMDAR autoantibody-associated psychiatric disease

Eligibility Criteria

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

You may not qualify if:

• Individuals eligible to participate in Cohort A must meet all the following criteria:
• The participant is a male or female who is of legal age to provide informed consent per local regulations, and ≤65 years of age at the time of informed consent. For the purposes of this study, the minimum age is 19 years in South Korea and 18 years in Australia.
• The participant, or their legally authorized representative (LAR), must be willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. For participants who are unable to sign the consent form themselves, informed consent must be obtained from their LAR in accordance with local regulations and ethical guidelines.
• The participant, or their LAR, must ensure willingness and ability to comply with all study procedures to the extent possible, as determined by the Investigator.
• The participant has a diagnosis of ANRE according to the Graus et al criteria (Graus et al, 2016), with symptom onset \>9 months to ≤36 months (or ≤120 months with Sponsor approval) prior to Week 0, Day 0.
• The participant has a positive cell-based assay result for CSF anti-NMDAR IgG autoantibody within 9 months of Week 0, Day 0. Participants without a positive CSF anti-NMDAR IgG autoantibody result within 9 months of Week 0, Day 0 may undergo a LP at Screening prior to the first study drug administration to confirm the presence of anti-NMDAR IgG autoantibodies in CSF (see Section 7.6.4.6.1).
• Participants treated with IVIG must have completed treatment at least 7 days prior to Week 0, Day 0.
• Participants previously treated with immunotherapy must be receiving a stable dose (per Investigator discretion) for ≥1 month before Week 0, Day 0.
• Participants who are taking psychiatric medications (anti-depressants and antipsychotics) must remain on stable background psychiatric medications for at least 4 weeks prior to Week 0, Day 0 and for at least the first 6 weeks after Week 0, Day 0.
• Adequate disease burden as defined as any one of the following (a to c) at Screening and Week 0, Day 0:
• a. Two of the following: i. WAIS-IV immediate recall score \<7 ii. TMT-A \>40 seconds iii. RAVLT score \<7 b. BDI-II total score ≥20. c. EQ 5D-5L score "moderate" or higher on at least 3 of the 5 items. Exceptions may be granted on a case-by-case basis in consultation with the Sponsor.
• No active malignancy (see Section 7.6.3.3) or residual teratoma. Prior teratoma must be fully resected ≥1 week before Week 0, Day 0 with no evidence of recurrence per work-up (imaging and tumor markers).
• Note: Discovery of a contralateral teratoma after study initiation will not be considered a protocol deviation. The event must be reported, managed per standard of care, and reviewed with the Sponsor Medical Monitor.
• Participants must have undergone appropriate cancer screening prior to study enrollment. The specific series of investigations used for each participant will occur according to the judgment of the treating Investigator (for example, MRI or CT of the chest, abdomen, and pelvis, and pelvic ultrasound for female participants) to exclude the presence or recurrence of an underlying neoplasm, such as ovarian teratoma or other malignancy. Documentation of imaging results must be available in the source documents.
• Sexually active female participants of childbearing potential and male participants with female partner(s) of childbearing potential must be willing to use a highly effective method of contraception during the study (from the time of providing consent) until at least 90 days after the last study drug administration, or longer if required by local regulations.

Sponsors & Collaborators

• Arialys Therapeutics: collaborator
• Arialys Australia Pty Ltd: lead

MeSH Terms

Conditions

Encephalitis; Autoimmune Diseases of the Nervous System

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Pete Flynn, PhD

  Arialys Therapeutics

  STUDY CHAIR

Central Study Contacts

April Purcell

CONTACT

1-619-865-6365; apurcell@arialysrx.com

Mari Maurer

CONTACT

1-415-827-6713; mmaurer@arialysrx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2025
• First Posted: July 30, 2025
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): May 30, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share