A Study to Test the Efficacy, Safety, and Pharmacokinetics of Rozanolixizumab in Adult Study Participants With Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the efficacy of rozanolixizumab as measured by seizure freedom, change in cognitive function, use of rescue medication, onset of seizure freedom and to assess safety and tolerability.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Rozanolixizumab in Adult Study Participants With Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis

Conditions
-----------------
Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis

Intervention / Treatment
-----------------
* Drug: Rozanolixizumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Study participant must be ≥18 to ≤89 years of age Study participant must be seropositive for leucine-rich glioma inactivated 1 (LGI1) antibody Study participant must have ≥2 seizures/week during the Screening Period or have experienced such seizures that stopped following high dose corticosteroids (500 to 1000 milligram (mg) methylprednisolone (MP) equivalent/day): Either faciobrachial dystonic seizures (FBDS) with or without other focal (partial) seizures including focal to bilateral tonic clonic Or focal (partial) seizures including focal to bilateral tonic clonic and fulfil the following new-onset Autoimmune encephalitis (AIE) criteria Study participant has initiated or re-initiated corticosteroids at a dose of 500 to 1000 mg MP equivalent/day within 42 days prior to randomization. Participants re-initiating corticosteroids are eligible only if re-initiation is due to seizure rebound and within the timeframe outlined. If the study participant has initiated a steroid taper, the study participant cannot receive an oral steroid dose lower than 40mg/day when randomized Study participant with onset of disease symptom between 0 to 12 months prior to Screening, per investigator's assessment. Study participant weighs at least 35 kg at Screening A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) OR ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 90 days after the final dose of study treatment Exclusion Criteria: Study participant has a known hypersensitivity to any components of the study medication or any other anti-neonatal Fc receptor (FcRn) medications. Study participant has a confirmed prior diagnosis of epilepsy or new onset seizures that are unrelated to LGI1 autoimmune encephalitis (AIE) or has any known or suspected medical cause for the onset of seizures other than possible AIE Study participant has a known active neoplastic disease or history of neoplastic disease within 5 years of study entry Study participant has renal impairment, defined as glomerular filtration rate (GFR) <30mL/min/1.73m2 at the Screening Visit Study participant has a clinically important active infection (including unresolved or not adequately treated infection) as assessed by investigator, including participants with a serious infection within 6 weeks prior to the first dose of investigational medicinal product (IMP) Study participant has a history of chronic ongoing infections Study participant has current unstable liver or biliary disease, per investigator assessment, defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis Study participant has positive tuberculosis (TB) test at the Screening Visit Study participant has a history of solid organ transplant or hematopoietic stem cell transplant Study participant has undergone a splenectomy Study participant has a current or medical history of primary immune deficiency Study participant has received a live vaccination within 4 weeks prior to the Baseline Visit; or intends to have a live vaccination during the course of the study or within 8 weeks following the final dose of investigational medicinal product (IMP) Study participant has previously received rozanolixizumab drug product Alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) are >3x upper limit of normal (ULN) Study participant has a total IgG level ≤5.5 g/L at the Screening Visit Study participant has absolute neutrophil count <1500 cells/mm^3 at the Screening Visit

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rozanolixizumab<br>Participants will be randomized to receive a predefined dose of rozanolixizumab. | Drug: Rozanolixizumab<br>* Pharmaceutical form: Solution for infusion Route of administration: Subcutaneous use Subjects will receive rozanolixizumab in a pre-specified sequence during the Treatment Period.<br>|
| Placebo Comparator: Placebo<br>Participants will be randomized to receive a dose of placebo. | Drug: Placebo<br>* Pharmaceutical form: Solution for infusion Route of administration: Subcutaneous use Subjects will receive placebo in a pre-specified sequence during the Treatment Period.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of seizure free study participants at the end of the Treatment Period | Seizure freedom is defined by 28 consecutive days of no seizures maintained until the end of the Treatment Period | From Baseline until the end of the Treatment Period (Week 25) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score at the end of the Treatment Period | The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) consists of 12 subtests that contribute to 5 age-based domain index scores (immediate memory, visuospatial/constructional, language, attention, delayed memory) that are aggregated for a total scale index score. Higher scores reflect better neurocognitive performance. | From Baseline until the end of the Treatment Period (Week 25) | 
| Proportion of participants with a favorable outcome in the Modified Rankin Scale (mRS) during the Treatment Period | Proportion of participants with a favorable outcome in the Modified Rankin Scale (mRS) during the Treatment Period, where favorable outcome is defined as no worsening for participants with a Baseline mRS score of ≤1 or improvement of ≥1 point for participants with a Baseline mRS score of ≥2 | From Baseline until the end of the Treatment Period (Week 25) | 
| Proportion of participants who required rescue medication due to an absence or loss of clinical benefit during the Treatment Period | Study participants who require rescue medication due to an absence or loss of clinical benefit will discontinue blinded treatment, and complete the assessments for the Early Discontinuation Visit. | From Baseline until the end of the Treatment Period (Week 25) | 
| Time to first occurrence of seizure freedom during the Treatment Period | The time to first occurrence of seizure freedom (TTFSF) is defined by the number of days after randomization to the first day of the first 28 consecutive days without seizures during the Treatment Period | From Baseline until the end of the Treatment Period (Week 25) | 
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline until the End of Study Visit (Week 32) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis, Phase 2, Rozanolixizumab