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

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

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.

Study Overview

• Status: Terminated
• Conditions: Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis
• Intervention / Treatment: Drug: Rozanolixizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Aie001 30027
• Belgium
  • Bruxelles, Belgium
    • Aie001 40123
• France
  • Bordeaux, France
    • Aie001 40129
  • Bron, France
    • Aie001 40426
  • Lille, France
    • Aie001 40364
  • Nancy, France
    • Aie001 40546
  • Nice, France
    • Aie001 40132
  • Paris, France
    • Aie001 40019
  • Toulouse Cedex, France
    • Aie001 40286
• Germany
  • Berlin, Germany
    • Aie001 40515
  • Kiel, Germany
    • Aie001 40249
• Italy
  • Pavia, Italy
    • Aie001 40695
  • Roma, Italy
    • Aie001 40567
• Netherlands
  • Rotterdam, Netherlands
    • Aie001 40264
• Spain
  • Barcelona, Spain
    • Aie001 40267
  • Málaga, Spain
    • Aie001 40341
• United Kingdom
  • Nottingham, United Kingdom
    • Aie001 40168
  • Oxford, United Kingdom
    • Aie001 40163
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045-2541
      • Aie001 50101
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Aie001 50342
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-3117
      • Aie001 50243
    • Boston, Massachusetts, United States, 02115
      • Aie001 50047
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Aie001 50104
  • New York
    • New York, New York, United States, 10016
      • Aie001 50298
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Aie001 50090
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Aie001 50311
  • Texas
    • Dallas, Texas, United States, 75390-8869
      • Aie001 50304

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seizure Free Study Participants at the End of the Treatment	Seizure freedom was defined as a minimum of 28 consecutive days of no seizures of any type during the treatment and maintained until the end of the treatment (Week 25).	From Baseline until the end of the Treatment (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	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 were aggregated for a total scale index score. All index scores have an age-based mean of 100, with a standard deviation (SD) of 15. The total scale score was calculated by taking the mean of the sum of the five index scores. Total possible scale index scores range from 40-135. Higher scores reflect better neurocognitive performance. The total scale index score is the score typically used to reflect global neurocognitive status. Baseline of RBANS is defined as the screening (Visit 1, Week -1) value.	From Baseline to Week 5, 13, 21 and 25
Percentage of Participants With a Favorable Outcome in the Modified Rankin Scale (mRS) During the Treatment	Percentage of participants with a favorable outcome in mRS during treatment, where favorable outcome defined as no worsening for participants with Baseline mRS score of ≤1 or improvement of ≥1 point for participants with Baseline mRS score of ≥2. The mRS is commonly used scale for measuring degree of disability or dependence in daily activities of people who suffered a stroke or other causes of neurological disability. The scale ranges from 0 (perfect health) to 6 (death). 0-No symptoms at all; No significant disability despite symptoms; able to carry out all usual activities; Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; Moderate disability; requiring some help, but able to walk without assistance; Moderately severe disability; unable to walk and attend to own bodily needs without assistance; Severe disability; bedridden, incontinent and requiring constant nursing care and attention; Dead	From Baseline until the end of the Treatment (Week 25)
Number of Participants Who Required Rescue Medication Due to an Absence or Loss of Clinical Benefit During the Treatment	Study participants who required rescue medication due to an absence or loss of clinical benefit were discontinued blinded treatment and completed the assessments for the early discontinuation visit.	From Baseline until the end of the Treatment (Week 25)
Time to First Occurrence of Seizure Freedom During the Treatment	The time to first occurrence of seizure freedom was defined by the number of days after randomization to the first day of the first 28 consecutive days without seizures during the treatment. Time to first occurrence of 28 consecutive days of seizure freedom (days) during the treatment was calculated as date of first day of occurrence of 28 consecutive days of seizure freedom - Date of Randomization + 1.	From Baseline until the end of the Treatment (Week 25)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP, whether or not related to the IMP. A TEAE was defined as an AE starting on or after the time of first administration of IMP or any unresolved event already present before the first administration of IMP that worsens in intensity following exposure to treatment up to the end of the Treatment and including the 8-week (56 days) Safety-Follow Up (SFU).	From Baseline until the End of Study (Week 32)

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL
• Investigators: Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2021
• Primary Completion (Actual): March 8, 2024
• Study Completion (Actual): April 26, 2024

Study Registration Dates

• First Submitted: May 3, 2021
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Phase 2; Rozanolixizumab; Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Autoimmune Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Epilepsy; Thyroid Diseases; Thyroiditis, Autoimmune; Thyroiditis; Glioma; Encephalitis; Epilepsies, Partial; Autoimmune Diseases of the Nervous System; Hashimoto Disease; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Rozanolixizumab
• Other Study ID Numbers: AIE001; 2019-004778-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No