Autoimmune Encephalitis (AE)
Conditions
Keywords
Autoimmune Encephalitis (AIE), Adolescents
Brief summary
The POLARIS study is designed to evaluate how well efgartigimod PH20 SC may work (called "efficacy") and how safe it is for people diagnosed with Autoimmune Encephalitis (AIE). The study consists of 4 parts: in part A participants will receive efgartigimod SC; in part B, participants will be randomized to receive either efgartigimod SC or placebo; in part C, participants who completed part B will receive efgartigimod SC; in part D, participants who completed part C will be observed after their last dose of efgartigimod SC. If AIE symptoms return, efgartigimod SC treatment may be restarted during this time. The maximum overall study duration for participants is up to 3 years. More information can be found in clinicaltrials.argenx.com/polaris
Detailed description
The study is designed to address the unmet need for effective immunomodulatory therapy in AIE, enrolling patients across multiple antibody-defined subgroups, with the anti-NMDAR encephalitis group serving as the primary cohort for statistical analysis.
Interventions
BIOLOGICALEfgartigimod PH20 (ARGX-113) SC
subcutaneous administrations of efgartigimod PH20 SC given by prefilled syringe (PFS). For participants aged 12 to \<18 years with body weight ≤50 kg, the study drug will be administered by vial and syringe.
OTHERPlacebo PH20 SC
subcutaneous administrations of placebo PH20 SC given by prefilled syringe (PFS). For participants aged 12 to \<18 years with body weight ≤50 kg, the study drug will be administered by vial and syringe
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is at least 12 years of age. * Meeting at least the criteria for possible AIE according to the Graus criteria. * Part A: Must not have received prior treatment for AIE with PLEX or Ig (participants may have received glucocorticoids); and must not have received PLEX or Ig for any other medical condition in the last 3 months \- Part B: Either completing Part A, or If directly entering Part B, must have received first-line treatment for AIE (i.e. corticosteroids, PLEX, and/or Ig) and have a CASE score of 3 or higher, or a score of 2 or higher in a single sub-item
Exclusion criteria
* Known anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody positivity. * Any medical condition that would interfere with an accurate assessment of clinical symptoms of AIE. * Recent major surgery (within 3 months of screening) or intention to have major surgery during the study, except for surgeries for AIE-related teratomas and thymomas. * History (within 12 months before screening) of current alcohol, drug (including recreational or prescribed cannabinoids), or medication abuse. * Psychiatric or cognitive impairment unrelated to AIE.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CASE score in the NMDAR population | up to week 24 | CASE= Clinical Assessment Scale in Autoimmune Encephalitis; NMDAR=N-methyl-D-aspartate receptor; Neuropsychological Status. The CASE (Clinical Assessment Scale in AIE) includes an assessment of 9 items: seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, weakness. This overall CASE total score ranges from 0 to 27, with a higher score indicating a greater degree of disability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in mRS | up to week 8 | The mRS (modified Rankin Scale) is commonly used to measure the degree of disability or dependence in the daily activities of people with neurological disabilities. Scores range from 0 (no symptoms) to 6(dead). |
| Change in CASE score | up to week 8 | The CASE (Clinical Assessment Scale in AIE) includes an assessment of 9 items: seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, weakness. This overall CASE total score ranges from 0 to 27, with a higher score indicating a greater degree of disability. |
| Change in MoCA total score | up to week 8 | MoCA= Montreal Cognitive Assessment |
| Change in NPI-C total score | up to week 8 | The NPI-C (Neuropsychiatric Inventory--Clinician) total score will be used as a global measure of neuropsychiatric symptoms.Total score is calculated by summing the scores of all the individual domains.Each domain score is determined by summing the item scores within that domain. The NPI-C uses a clinician rating method, where ratings for frequency, severity, and caregiver distress are provided for each item.These item scores are then summed to create a total domain score. |
| Change from baseline in CGI-S | up to week 8 | Expression of Change. CGI is a clinician-rated scale that measures illness severity (CGI-S) and global improvement or change (CGI-C).It is rated on a 7-point scale, from 1 (normal) to 7 (amongst the most severely ill patients) for CGI-S and from 1 (very much improved) to 7 (very much worse) for CGI-C. PGI-S and PGI-C are the patient-reported counterparts to CGI-S and CGI-C, respectively. |
| Change from baseline in PGI-S | up to week 8 | A Impression of Severity; PGI-S= Patient Global Impression Scale. PGI-S and PGI-C are the patient-reported counterparts to CGI-S and CGI-C, respectively. |
| Change from baseline in CGI-C | up to week 8 | CGI-C= Clinical Global Expression of Change . CGI is a clinician-rated scale that measures illness severity (CGI-S) and global improvement or change (CGI-C).It is rated on a 7-point scale, from 1 (normal) to 7 (amongst the most severely ill patients) for CGI-S and from 1 (very much improved) to 7 (very much worse) for CGI-C. PGI-S and PGI-C are the patient-reported counterparts to CGI-S and CGI-C, respectively. |
| Change from baseline in PGI-C | up to week 8 | A Impression of Severity; PGI-C= Patient Global Expression of Change . PGI-S and PGI-C are the patient-reported counterparts to CGI-S and CGI-C, respectively. |
| Incidence and severity of AEs | up to week 8 | AEs= Adverse Effects |
| Incidence and severity of SAEs | up to week 8 | SAEs = Serious Adverse Effects |
| Trough efgartigimod serum concentrations over time | up to week 8 | — |
| Percent change from baseline in total IgG levels in serum over time | up to week 8 | IgG= Immunoglobulin G |
| Incidence and prevalence of ADA against efgartigimod in serum over time | up to week 8 | ADA = antidrug antibody(ies) |
| Incidence and prevalence of antibodies against rHuPH20 in plasma over time | up to week 8 | rHuPH20 = Recombinant Human Hyaluronidase PH20 |
| Change in mRS in the NMDAR population | up to week 24 | The mRS (modified Rankin Scale) is commonly used to measure the degree of disability or dependence in the daily activities of people with neurological disabilities. Scores range from 0 (no symptoms) to 6(dead) |
| Change in NPI-C total score in the NMDAR population | up to week 24 | NPI-C=Neuropsychiatric Inventory-Clinician; NMDAR=N-methyl-D-aspartate receptor. The NPI-C (Neuropsychiatric Inventory--Clinician) total score will be used as a global measure of neuropsychiatric symptoms. Total score is calculated by summing the scores of all the individual domains. Each domain score is determined by summing the item scores within that domain. The NPI-C uses a clinician rating method, where ratings for frequency, severity, and caregiver distress are provided for each item.These item scores are then summed to create a total domain score. |
| Change in RBANS in the NMDAR population | up to week 24 | RBANS=Repeatable Battery for the Assessment of Neuropsychological Status; NMDAR=N-methyl-D-aspartate receptor. The RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) is a performance outcome measure developed to identify and characterize cognitive impairment by assessing an individual's current level of cognitive performance. |
| Percentage of CASE responders in the NMDAR population. | at week 24 | CASE = Clinical Assessment Scale in AIE ; NMDAR=N-methyl-D-aspartate receptor |
| Change in CASE score in the non-NMDAR population | up to week 24 | CASE = Clinical Assessment Scale in AIE; NMDAR=N-methyl. The CASE (Clinical Assessment Scale in AIE) includes an assessment of 9 items: seizure,memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, weakness. This overall CASE total score ranges from 0 to 27, with a higher score indicating a greater degree of disability. |
| Change in RBANS in the non-NMDAR population | up to week 24 | RBANS= Repeatable Battery for the Assessment of Neuropsychological Status; NMDAR=N-methyl-D-aspartate receptor. The RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) is a performance outcome measure developed to identify and characterize cognitive impairment by assessing an individual's current level of cognitive performance. |
| Change in NPI-C total score in the non-NMDAR population | up to week 24 | NPI-C= Neuropsychiatric Inventory-Clinician; NMDAR=N-methyl-D-aspartate receptor. The NPI-C Neuropsychiatric Inventory--Clinician) total score will be used as a global measure of neuropsychiatric symptoms. Total score is calculated by summing the scores of all the individual domains. Each domain score is determined by summing the item scores within that domain. The NPI-C uses a clinician rating method, where ratings for frequency, severity, and caregiver distress are provided for each item. |
| Percentage of CASE responders in the non-NMDAR population. | at week 24 | CASE = Clinical Assessment Scale in AIE ; NMDAR=N-methyl-D-aspartate receptor. The CASE (Clinical Assessment Scale in AIE) includes an assessment of 9 items: seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, weakness. This overall CASE total score ranges from 0 to 27, with a higher score indicating a greater degree of disability. |
| Proportion of participants with presence of neuropsychiatric symptoms, defined by NPI-C total score of at least 1 point | at week 24 | NPI-C= Neuropsychiatric Inventory-Clinician. The NPI-C (Neuropsychiatric Inventory--Clinician) total score will be used as a global measure of neuropsychiatric symptoms. Total score is calculated by summing the scores of all the individual domains. Each domain score is determined by summing the item scores within that domain. The NPI-C uses a clinician rating method, where ratings for frequency, severity, and caregiver distress are provided for each item. |
| Proportion of participants with a favorable outcome in mRS where favorable outcome is defined as no worsening for participants with a baseline mRS score of ≤2 or improvement of ≥1 point for participants with a baseline mRS score of >2 | up to week 24 | mRS=modified Rankin Scale. The mRS (modified Rankin Scale) is commonly used to measure the degree of disability or dependence in the daily activities of people with neurological disabilities. Scores range from 0 (no symptoms) to 6 (dead). |
| Change in CGI-S | up to week 24 | CGI-S= Clinical Global Impression of Severity. CGI is a clinician-rated scale that measures illness severity (CGI-S) and global improvement or change (CGI-C).It is rated on a 7-point scale, from 1 (normal) to 7 (amongst the most severely ill patients) for CGI-S and from 1 (very much improved) to 7 (very much worse) for CGI-C. |
| Change in CGI-C | up to week 24 | CGI-C= Clinical Global Impression of Change. CGI is a clinician-rated scale that measures illness severity (CGI-S) and global improvement or change (CGI-C).It is rated on a 7-point scale, from 1 (normal) to 7 (amongst the most severely ill patients) for CGI-S and from 1 (very much improved) to 7 (very much worse) for CGI-C. |
| Change in PGI-C | week 0 to week 24 | PGI-C =Patient Global Expression of Change. PGI-S and PGI-C are the patient-reported counterparts to CGI-S and CGI-C, respectively. |
| Change in PGI-S | week 0 to week 24 | PGI-S= Patient Global Expression of Severity. PGI-S and PGI-C are the patient-reported counterparts to CGI-S and CGI-C, respectively. |
| Time to resolution of status epilepticus | up to 24 weeks | — |
| Time to first occurrence of seizure freedom. | up to 24 weeks | Seizure freedom is defined as no seizures for at least 28 consecutive days |
| Proportion of participants with seizure freedom for at least the 28 consecutive days | up to 24 weeks | — |
| Time to use of rescue therapy after randomization | up to 24 weeks | — |
| Percent change in total IgG levels in serum | up to 24 weeks | IgG = Immunoglobulin G |
| Change in CASE score in the NMDAR population compared with the non-NMDAR population | up to 24 weeks | CASE = Clinical Assessment Scale in AIE ; NMDAR=N-methyl-D-aspartate receptor. . The CASE (Clinical Assessment Scale in AIE) includes an assessment of 9 items: seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, weakness. This overall CASE total score ranges from 0 to 27, with a higher score indicating a greater degree of disability. |
| Change in RBANS total score | week 24 to week 48 | The RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) is a performance outcome measure developed to identify and characterize cognitive impairment by assessing an individual's current level of cognitive performance. |
| Percentage of participants with maintained change in the CASE total score (defined as stable or improving) | week 24 to week 48 | The CASE (Clinical Assessment Scale in AIE) includes an assessment of 9 items: seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, weakness. This overall CASE total score ranges from 0 to 27, with a higher score indicating a greater degree of disability. |
| Percentage of participants with maintained mRS score (defined as stable or improving) | week 24 to week 48 | The mRS (modified Rankin Scale) is commonly used to measure the degree of disability or dependence in the daily activities of people with neurological disabilities. Scores range from 0 (no symptoms) to 6 (dead). |
| Proportion of participants requiring rescue or second-line AIE therapies | week 24 to week 48 | AIE = Auto-Immune Encephalitis |
| Time to participants requiring rescue or second-line AIE therapies | week 24 to week 48 | AIE = Auto-Immune Encephalitis |
| Change in CASE | week 24 to week 48 | The CASE (Clinical Assessment Scale in AIE) includes an assessment of 9 items: seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, weakness. This overall CASE total score ranges from 0 to 27, with a higher score indicating a greater degree of disability. |
| Change in mRs | week 24 to week 48 | The mRS (modified Rankin Scale) is commonly used to measure the degree of disability or dependence in the daily activities of people with neurological disabilities. Scores range from 0 (no symptoms) to 6 (dead). |
| Change in RBANS | week 24 to week 48 | The RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) is a performance outcome measure developed to identify and characterize cognitive impairment by assessing an individual's current level of cognitive performance. |
| Proportion of participants with seizure freedom for at least the 28 consecutive days preceding the participants in final Part of trial | week 24 to week 48 | mRS=modified Rankin Scale |
| Change in mRS in the non-NMDAR population | up to week 24 | mRS= modified Rankin Scale; NMDAR=N-methyl-D-aspartate receptor. The mRS (modified Rankin Scale) is commonly used to measure the degree of disability or dependence in the daily activities of people with neurological disabilities.Scores range from 0 (no symptoms) to 6 (dead). |
| Incidence and prevalence of ADA against efgartigimod in serum | week 24 to week 48 | ADA = antidrug antibody(ies) |
Countries
United States
Contacts
CONTACTSabine Coppieters, MD
Outcome results
None listed