A Study to Learn About How Well the Medicine Efgartigimod Works to Treat Autoimmune Encephalitis In Children 12 Years or Older and Adults (Polaris)

A Global, Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult and Adolescent Participants With Autoimmune Encephalitis

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

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Encephalitis (AE)
• Intervention / Treatment: Biological: Efgartigimod PH20 (ARGX-113) SC; Other: Placebo PH20 SC

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.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (Open-Label Lead-in Period): Efgartigimod PH20 SC; All participants will receive efgartigimod PH20 SC open label for 8 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.
Experimental: Part B (Double-blinded treatment period): Efgartigimod PH20 SC; Participants 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.
Placebo Comparator: Part B (Maintenance double-blinded treatment period): Placebo PH20 SC; Participants will receive placebo for 24 weeks	Other: Placebo 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
Experimental: Part C (Open-Label Extension Period): Efgartigimod 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	up to week 8
Change in MoCA total score	MoCA= Montreal Cognitive Assessment	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.	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.	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.	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.	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.	up to week 8
Incidence and severity of AEs	AEs= Adverse Effects	up to week 8
Incidence and severity of SAEs	SAEs = Serious Adverse Effects	up to week 8
Trough efgartigimod serum concentrations over time		up to week 8
Percent change from baseline in total IgG levels in serum over time	IgG= Immunoglobulin G	up to week 8
Incidence and prevalence of ADA against efgartigimod in serum over time	ADA = antidrug antibody(ies)	up to week 8
Incidence and prevalence of antibodies against rHuPH20 in plasma over time	rHuPH20 = Recombinant Human Hyaluronidase PH20	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)	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.	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.	up to week 24
Percentage of CASE responders in the NMDAR population.	CASE = Clinical Assessment Scale in AIE ; NMDAR=N-methyl-D-aspartate receptor	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.	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.	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.	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).	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.	at week 24
Incidence and severity of AEs	AEs = Adverse Effects	week 24 onwards
Incidence and severity of SAEs	SAEs = Serious Adverse Effects	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.	at week 24
Change in MoCA total score	MoCA= Montreal Cognitive Assessment	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).	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.	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.	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.	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.	week 0 to week 24
Time to resolution of status epilepticus		up to 24 weeks
Time to first occurrence of seizure freedom.	Seizure freedom is defined as no seizures for at least 28 consecutive days	up to 24 weeks
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
Trough efgartigimod serum concentrations over time		up to 24 weeks
Percent change in total IgG levels in serum	IgG = Immunoglobulin G	up to 24 weeks
Incidence and prevalence of ADA against efgartigimod in serum over time	ADA = anti drug antibodies	up to 24 weeks
Incidence and prevalence of antibodies against rHuPH20 in plasma over time	rHuPH20 = Recombinant Human Hyaluronidase PH20	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.	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.	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.	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).	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.	week 24 to week 48
Proportion of participants requiring rescue or second-line AIE therapies	AIE = Auto-Immune Encephalitis	week 24 to week 48
Time to participants requiring rescue or second-line AIE therapies	AIE = Auto-Immune Encephalitis	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.	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).	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.	week 24 to week 48
Time to resolution of status epilepticus		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	week 24 to week 48
Incidence and prevalence of ADA against efgartigimod in serum	ADA = antidrug antibody(ies)	week 24 to week 48
Percent change in total IgG levels in serum	IgG = Immunoglobulin G	week 24 to week 48

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Estimated): July 13, 2026
• Primary Completion (Estimated): December 4, 2030
• Study Completion (Estimated): July 26, 2031

Study Registration Dates

• First Submitted: May 7, 2026
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Adolescents; Autoimmune Encephalitis (AIE)
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; efgartigimod alfa
• Other Study ID Numbers: ARGX-113-22-AIE-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No