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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- argenx
- 入组人数
- 170
- 试验地点
- 2
- 主要终点
- Change in CASE score in the NMDAR population
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is at least 12 years of age.
- •Meeting at least the criteria for possible AIE according to the Graus criteria.
- •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
排除标准
- •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.
研究组 & 干预措施
Part C (Open-Label Extension Period): Efgartigimod PH20 SC
Participants who complete Part B will receive efgartigimod PH20 SC for 24 weeks
干预措施: Efgartigimod PH20 (ARGX-113) SC (Biological)
Part A (Open-Label Lead-in Period): Efgartigimod PH20 SC
All participants will receive efgartigimod PH20 SC open label for 8 weeks
干预措施: Efgartigimod PH20 (ARGX-113) SC (Biological)
Part B (Double-blinded treatment period): Efgartigimod PH20 SC
Participants will receive efgartigimod PH20 SC for 24 weeks
干预措施: Efgartigimod PH20 (ARGX-113) SC (Biological)
Part B (Maintenance double-blinded treatment period): Placebo PH20 SC
Participants will receive placebo for 24 weeks
干预措施: Placebo PH20 SC (Other)
结局指标
主要结局
Change in CASE score in the NMDAR population
时间窗: 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.
次要结局
- Trough efgartigimod serum concentrations over time(up to 24 weeks)
- Percent change in total IgG levels in serum(up to 24 weeks)
- Incidence and prevalence of ADA against efgartigimod in serum over time(up to 24 weeks)
- Incidence and prevalence of antibodies against rHuPH20 in plasma over time(up to 24 weeks)
- Change in CASE score in the NMDAR population compared with the non-NMDAR population(up to 24 weeks)
- Change in RBANS total score(week 24 to week 48)
- Change in mRS(up to week 8)
- Change in CASE score(up to week 8)
- Change in MoCA total score(up to week 8)
- Change in NPI-C total score(up to week 8)
- Change from baseline in CGI-S(up to week 8)
- Change from baseline in PGI-S(up to week 8)
- Change from baseline in CGI-C(up to week 8)
- Change from baseline in PGI-C(up to week 8)
- Incidence and severity of AEs(up to week 8)
- Incidence and severity of SAEs(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(up to week 8)
- Incidence and prevalence of ADA against efgartigimod in serum over time(up to week 8)
- Incidence and prevalence of antibodies against rHuPH20 in plasma over time(up to week 8)
- Change in mRS in the NMDAR population(up to week 24)
- Change in NPI-C total score in the NMDAR population(up to week 24)
- Change in RBANS in the NMDAR population(up to week 24)
- Percentage of CASE responders in the NMDAR population.(at week 24)
- Change in CASE score in the non-NMDAR population(up to week 24)
- Change in RBANS in the non-NMDAR population(up to week 24)
- Change in NPI-C total score in the non-NMDAR population(up to week 24)
- Change in mRS in the non-NMDAR population(up to week 24)
- Percentage of CASE responders in the non-NMDAR population.(at week 24)
- Incidence and severity of AEs(week 24 onwards)
- Incidence and severity of SAEs(week 24 onwards)
- Proportion of participants with presence of neuropsychiatric symptoms, defined by NPI-C total score of at least 1 point(at week 24)
- Change in MoCA total score(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(up to week 24)
- Change in CGI-S(up to week 24)
- Change in CGI-C(up to week 24)
- Change in PGI-C(week 0 to week 24)
- Change in PGI-S(week 0 to week 24)
- Time to resolution of status epilepticus(up to 24 weeks)
- Time to first occurrence of seizure freedom.(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)
- Percentage of participants with maintained change in the CASE total score (defined as stable or improving)(week 24 to week 48)
- Percentage of participants with maintained mRS score (defined as stable or improving)(week 24 to week 48)
- Change in NPI-C total score(week 24 to week 48)
- Proportion of participants requiring rescue or second-line AIE therapies(week 24 to week 48)
- Time to participants requiring rescue or second-line AIE therapies(week 24 to week 48)
- Change in CASE(week 24 to week 48)
- Change in mRs(week 24 to week 48)
- Change in RBANS(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(week 24 to week 48)
- Incidence and prevalence of ADA against efgartigimod in serum(week 24 to week 48)
- Percent change in total IgG levels in serum(week 24 to week 48)