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: Active, not recruiting
• 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 Contact: Name: UCB Cares; Phone Number: 1-844-599-2273 (USA); Email: ucbcares@ucb.com
• Study Contact Backup: Name: UCB Cares; Phone Number: 0018445992273; Email: ucbcares@ucb.com

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
  • Trento, Italy
    • Aie001 40561
• 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
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 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)
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)

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 (Estimated): February 14, 2025
• Study Completion (Estimated): February 14, 2025

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 (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

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