A Phase 2 interventional study of Efgartigimod PH20 (ARGX-113) SC and Placebo PH20 SC in Autoimmune Encephalitis (AE), sponsored by argenx. Not yet recruiting at 2 sites in United States. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by argenx · Phase 2, Interventional, and Treatment
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
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.
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:
All participants will receive efgartigimod PH20 SC open label for 8 weeks
Biological: Efgartigimod PH20 (ARGX-113) SC
Participants will receive efgartigimod PH20 SC for 24 weeks
Biological: Efgartigimod PH20 (ARGX-113) SC
Participants will receive placebo for 24 weeks
Other: Placebo PH20 SC
Participants who complete Part B will receive efgartigimod PH20 SC for 24 weeks
Biological: Efgartigimod 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.
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
Change in CASE score in the NMDAR population
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.
Time frame: up to week 24
Change in mRS
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).
Time frame: up to week 8
Change in CASE score
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.
Time frame: up to week 8
Change in MoCA total score
MoCA= Montreal Cognitive Assessment
Time frame: up to week 8
Change in NPI-C total score
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.
Time frame: up to week 8
Change from baseline in CGI-S
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.
Time frame: up to week 8
Change from baseline in PGI-S
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.
Time frame: up to week 8
Change from baseline in CGI-C
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.
Time frame: up to week 8
Change from baseline in PGI-C
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.
Time frame: up to week 8
Incidence and severity of AEs
AEs= Adverse Effects
Time frame: up to week 8
Incidence and severity of SAEs
SAEs = Serious Adverse Effects
Time frame: up to week 8
Trough efgartigimod serum concentrations over time
Time frame: up to week 8
Percent change from baseline in total IgG levels in serum over time
IgG= Immunoglobulin G
Time frame: up to week 8
Incidence and prevalence of ADA against efgartigimod in serum over time
ADA = antidrug antibody(ies)
Time frame: up to week 8
Incidence and prevalence of antibodies against rHuPH20 in plasma over time
rHuPH20 = Recombinant Human Hyaluronidase PH20
Time frame: up to week 8
Change in mRS in the NMDAR population
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)
Time frame: up to week 24
Change in NPI-C total score in the NMDAR population
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.
Time frame: up to week 24
Change in RBANS in the NMDAR population
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.
Time frame: up to week 24
Percentage of CASE responders in the NMDAR population.
CASE = Clinical Assessment Scale in AIE ; NMDAR=N-methyl-D-aspartate receptor
Time frame: at week 24
Change in CASE score in the non-NMDAR population
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.
Time frame: up to week 24
Change in RBANS in the non-NMDAR population
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.
Time frame: up to week 24
Change in NPI-C total score in the non-NMDAR population
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.
Time frame: up to week 24
Change in mRS in the non-NMDAR population
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).
Time frame: up to week 24
Percentage of CASE responders in the non-NMDAR population.
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.
Time frame: at week 24
Incidence and severity of AEs
AEs = Adverse Effects
Time frame: week 24 onwards
Incidence and severity of SAEs
SAEs = Serious Adverse Effects
Time frame: week 24 onwards
Proportion of participants with presence of neuropsychiatric symptoms, defined by NPI-C total score of at least 1 point
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.
Time frame: at week 24
Change in MoCA total score
MoCA= Montreal Cognitive Assessment
Time frame: up to week 24
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
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).
Time frame: up to week 24
Change in CGI-S
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.
Time frame: up to week 24
Change in CGI-C
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.
Time frame: up to week 24
Change in PGI-C
PGI-C =Patient Global Expression of Change. PGI-S and PGI-C are the patient-reported counterparts to CGI-S and CGI-C, respectively.
Time frame: week 0 to week 24
Change in PGI-S
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 frame: week 0 to week 24
Time to resolution of status epilepticus
Time frame: up to 24 weeks
Time to first occurrence of seizure freedom.
Seizure freedom is defined as no seizures for at least 28 consecutive days
Time frame: up to 24 weeks
Proportion of participants with seizure freedom for at least the 28 consecutive days
Time frame: up to 24 weeks
Time to use of rescue therapy after randomization
Time frame: up to 24 weeks
Trough efgartigimod serum concentrations over time
Time frame: up to 24 weeks
Percent change in total IgG levels in serum
IgG = Immunoglobulin G
Time frame: up to 24 weeks
Incidence and prevalence of ADA against efgartigimod in serum over time
ADA = anti drug antibodies
Time frame: up to 24 weeks
Incidence and prevalence of antibodies against rHuPH20 in plasma over time
rHuPH20 = Recombinant Human Hyaluronidase PH20
Time frame: up to 24 weeks
Change in CASE score in the NMDAR population compared with the non-NMDAR population
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.
Time frame: up to 24 weeks
Change in RBANS total score
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.
Time frame: week 24 to week 48
Percentage of participants with maintained change in the CASE total score (defined as stable or improving)
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.
Time frame: week 24 to week 48
Percentage of participants with maintained mRS score (defined as stable or improving)
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).
Time frame: week 24 to week 48
Change in NPI-C total score
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.
Time frame: week 24 to week 48
Proportion of participants requiring rescue or second-line AIE therapies
AIE = Auto-Immune Encephalitis
Time frame: week 24 to week 48
Time to participants requiring rescue or second-line AIE therapies
AIE = Auto-Immune Encephalitis
Time frame: week 24 to week 48
Change in CASE
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.
Time frame: week 24 to week 48
Change in mRs
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).
Time frame: week 24 to week 48
Change in RBANS
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.
Time frame: week 24 to week 48
Time to resolution of status epilepticus
Time frame: week 24 to week 48
Proportion of participants with seizure freedom for at least the 28 consecutive days preceding the participants in final Part of trial
mRS=modified Rankin Scale
Time frame: week 24 to week 48
Incidence and prevalence of ADA against efgartigimod in serum
ADA = antidrug antibody(ies)
Time frame: week 24 to week 48
Percent change in total IgG levels in serum
IgG = Immunoglobulin G
Time frame: week 24 to week 48
Plan to share: No
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