Anti-N-methyl-D-aspartate Receptor (NMDAR) Encephalitis (ANRE), Anti-N-methyl-D-aspartate Receptor (NMDAR) Antibody-associated Psychiatric Disease, Autoimmune Encephalitis
Conditions
Keywords
Anti-N-methyl-D-aspartate receptor (NMDAR), Encephalitis, Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis
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
Detailed description
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common causes of autoimmune encephalitis. The disease is caused by the development of autoantibodies against the amino (N)-terminal domain (NTD) of the NMDAR subunit 1 (NR1) that bind and cross link the receptors, leading to receptor internalization and loss of function. Arialys has developed a monovalent (one-armed) antibody, ART5803, 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. There is also an increasing body of data supporting the potential link between broader psychiatric diseases and the presence of autoantibodies against the NMDAR.
Interventions
DRUGART5803
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
DRUGART5803-Cohort D
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.
Sponsors
Arialys Australia Pty Ltd
Arialys Therapeutics
Seoul National University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
7.3.1 Inclusion Criteria Individuals in Cohort A (participants with chronic ANRE) must meet all of the study inclusion criteria in Section 7.3.1.1. Individuals enrolled in Cohort B or Cohort C (participants with subacute or acute ANRE) must meet all of the study inclusion criteria in Section 7.3.1.2. Individuals in Cohort D (participants with anti-NMDAR autoantibody associated psychiatric disease) must meet all of the study inclusion criteria in Section 7.3.1.3. Eligibility for participation in this study will be determined solely based on the participant meeting all protocol-defined inclusion and
Exclusion criteria
. The legally authorized representative (LAR), where applicable, may provide informed consent on behalf of a participant who lacks the capacity to provide consent in accordance with local regulations; however, the LAR does not independently satisfy eligibility criteria. A participant who does not meet all required inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the safety and tolerability of ART5803 | 26 weeks | Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the changes in neurological and behavioral outcomes following ART5803 administration | 11 weeks | Change from baseline in Clinical Assessment Scale for Autoimmune Encephalitis (CASE) outcomes (Score range: 0-27. Higher score indicated worse symptoms) |
| To assess changes in mobility and disability in basic and instrumental activities in daily living outcomes following ART5803 administration | 26 weeks | In absence of rescue therapy: Proportion of participants with ≥1 point improvement in mRS from baseline to Week 11 Change from baseline in mRS score at Week 1, 3, 7, 11, 16, 20, 26 and ET/EOS as determined by rank analyses, integrating need for rescue therapy and time to achievement of the mRS Time to mRS improvement from baseline by ≥1 point (Speed of Recovery) Time to mRS ≤2 |
| To assess the effects of ART5803 on neuropsychological assessments | 26 weeks | Change from baseline in neuropsychological endpoints: Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) Digit Span (Score varies) (Cohort A only) |
| Cerebrospinal Fluid (CSF) PK parameters of ART5803 | 12 weeks | To characterize and compare the PK profile of ART5803 as measured by maximum concentration (Cmax) |
| To assess the effects of ART5803 on Patient Reported Outcomes (PROs) | 26 weeks | Change from baseline in patient reported endpoints: Short Form Health Survey, Version 2 (SF-36-II) mental component domain score (Score range: 0-100. Higher score indicated better symptoms) (Cohort A only) |
| Serum PK parameters of ART5803 | 26 weeks | To characterize and compare the PK profile of ART5803 as measured by maximum concentration (Cmax) |
Countries
South Korea
Contacts
CONTACTApril Purcell
CONTACTMari Maurer
STUDY_CHAIRPete Flynn, PhD
Arialys Therapeutics
Outcome results
None listed