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NCT Number: NCT07583641

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

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

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Key information

Conditions

Autoimmune Encephalitis (AE) Autoimmune Diseases Autoimmune Diseases of the Nervous System Immune System Diseases Nervous System Diseases

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Efgartigimod PH20 (ARGX-113) SC

Biological

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 PH20 SC

Other

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

Primary outcomes

  1. Change in CASE score in the NMDAR population

    Time frame: 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 outcomes

  1. Change in mRS

    Time frame: 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).

  2. Change in CASE score

    Time frame: 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.

  3. Change in MoCA total score

    Time frame: up to week 8

    MoCA= Montreal Cognitive Assessment

  4. Change in NPI-C total score

    Time frame: 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.

  5. Change from baseline in CGI-S

    Time frame: 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.

  6. Change from baseline in PGI-S

    Time frame: 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.

  7. Change from baseline in CGI-C

    Time frame: 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.

  8. Change from baseline in PGI-C

    Time frame: 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.

  9. Incidence and severity of AEs

    Time frame: up to week 8

    AEs= Adverse Effects

  10. Incidence and severity of SAEs

    Time frame: up to week 8

    SAEs = Serious Adverse Effects

  11. Trough efgartigimod serum concentrations over time

    Time frame: up to week 8

  12. Percent change from baseline in total IgG levels in serum over time

    Time frame: up to week 8

    IgG= Immunoglobulin G

  13. Incidence and prevalence of ADA against efgartigimod in serum over time

    Time frame: up to week 8

    ADA = antidrug antibody(ies)

  14. Incidence and prevalence of antibodies against rHuPH20 in plasma over time

    Time frame: up to week 8

    rHuPH20 = Recombinant Human Hyaluronidase PH20

  15. Change in mRS in the NMDAR population

    Time frame: 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)

  16. Change in NPI-C total score in the NMDAR population

    Time frame: 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.

  17. Change in RBANS in the NMDAR population

    Time frame: 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.

  18. Percentage of CASE responders in the NMDAR population.

    Time frame: at week 24

    CASE = Clinical Assessment Scale in AIE ; NMDAR=N-methyl-D-aspartate receptor

  19. Change in CASE score in the non-NMDAR population

    Time frame: 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.

  20. Change in RBANS in the non-NMDAR population

    Time frame: 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.

  21. Change in NPI-C total score in the non-NMDAR population

    Time frame: 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.

  22. Change in mRS in the non-NMDAR population

    Time frame: 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).

  23. Percentage of CASE responders in the non-NMDAR population.

    Time frame: 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.

  24. Incidence and severity of AEs

    Time frame: week 24 onwards

    AEs = Adverse Effects

  25. Incidence and severity of SAEs

    Time frame: week 24 onwards

    SAEs = Serious Adverse Effects

  26. Proportion of participants with presence of neuropsychiatric symptoms, defined by NPI-C total score of at least 1 point

    Time frame: 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.

  27. Change in MoCA total score

    Time frame: up to week 24

    MoCA= Montreal Cognitive Assessment

  28. 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

    Time frame: 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).

  29. Change in CGI-S

    Time frame: 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.

  30. Change in CGI-C

    Time frame: 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.

  31. Change in PGI-C

    Time frame: 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.

  32. Change in PGI-S

    Time frame: 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.

  33. Time to resolution of status epilepticus

    Time frame: up to 24 weeks

  34. Time to first occurrence of seizure freedom.

    Time frame: up to 24 weeks

    Seizure freedom is defined as no seizures for at least 28 consecutive days

  35. Proportion of participants with seizure freedom for at least the 28 consecutive days

    Time frame: up to 24 weeks

  36. Time to use of rescue therapy after randomization

    Time frame: up to 24 weeks

  37. Trough efgartigimod serum concentrations over time

    Time frame: up to 24 weeks

  38. Percent change in total IgG levels in serum

    Time frame: up to 24 weeks

    IgG = Immunoglobulin G

  39. Incidence and prevalence of ADA against efgartigimod in serum over time

    Time frame: up to 24 weeks

    ADA = anti drug antibodies

  40. Incidence and prevalence of antibodies against rHuPH20 in plasma over time

    Time frame: up to 24 weeks

    rHuPH20 = Recombinant Human Hyaluronidase PH20

  41. Change in CASE score in the NMDAR population compared with the non-NMDAR population

    Time frame: 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.

  42. Change in RBANS total score

    Time frame: 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.

  43. Percentage of participants with maintained change in the CASE total score (defined as stable or improving)

    Time frame: 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.

  44. Percentage of participants with maintained mRS score (defined as stable or improving)

    Time frame: 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).

  45. Change in NPI-C total score

    Time frame: week 24 to week 48

    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.

  46. Proportion of participants requiring rescue or second-line AIE therapies

    Time frame: week 24 to week 48

    AIE = Auto-Immune Encephalitis

  47. Time to participants requiring rescue or second-line AIE therapies

    Time frame: week 24 to week 48

    AIE = Auto-Immune Encephalitis

  48. Change in CASE

    Time frame: 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.

  49. Change in mRs

    Time frame: 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).

  50. Change in RBANS

    Time frame: 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.

  51. Time to resolution of status epilepticus

    Time frame: week 24 to week 48

  52. Proportion of participants with seizure freedom for at least the 28 consecutive days preceding the participants in final Part of trial

    Time frame: week 24 to week 48

    mRS=modified Rankin Scale

  53. Incidence and prevalence of ADA against efgartigimod in serum

    Time frame: week 24 to week 48

    ADA = antidrug antibody(ies)

  54. Percent change in total IgG levels in serum

    Time frame: week 24 to week 48

    IgG = Immunoglobulin G

Study contacts

Contact information is provided by the study sponsor or research team.

Sabine Coppieters, MD

CONTACT

[email protected]

857-350-4834

Sponsors and collaborators

Lead sponsor

argenx

Industry

Registry information

Official study title

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

Acronym: Polaris

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
May 13, 2026
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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