A Study to Test 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
- Interventions
- Drug: Placebo
- Registration Number
- NCT04875975
- Lead Sponsor
- UCB Biopharma SRL
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
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Study participant must be ≥18 to ≤89 years of age
-
Study participant must be seropositive for leucine-rich glioma inactivated 1 (LGI1) antibody
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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
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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
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Study participant with onset of disease symptom between 0 to 12 months prior to Screening, per investigator's assessment.
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Study participant weighs at least 35 kg at Screening
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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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will be randomized to receive a dose of placebo. Rozanolixizumab Rozanolixizumab Participants will be randomized to receive a predefined dose of rozanolixizumab.
- Primary Outcome Measures
Name Time Method Proportion of seizure free study participants at the end of the Treatment Period From Baseline until the end of the Treatment Period (Week 25) Seizure freedom is defined by 28 consecutive days of no seizures maintained until the end of the Treatment Period
- Secondary Outcome Measures
Name Time Method Change from Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score at the end of the Treatment Period From Baseline until the end of the Treatment Period (Week 25) 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.
Proportion of participants who required rescue medication due to an absence or loss of clinical benefit during the Treatment Period From Baseline until the end of the Treatment Period (Week 25) 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.
Time to first occurrence of seizure freedom during the Treatment Period From Baseline until the end of the Treatment Period (Week 25) 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
Proportion of participants with a favorable outcome in the Modified Rankin Scale (mRS) during the Treatment Period 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, 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
Incidence of Treatment-Emergent Adverse Events (TEAEs) From Baseline until the End of Study Visit (Week 32) 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.
Trial Locations
- Locations (27)
Aie001 50342
🇺🇸Jacksonville, Florida, United States
Aie001 50298
🇺🇸New York, New York, United States
Aie001 50090
🇺🇸Winston-Salem, North Carolina, United States
Aie001 40129
🇫🇷Bordeaux, France
Aie001 30027
🇦🇺Melbourne, Australia
Aie001 40123
🇧🇪Bruxelles, Belgium
Aie001 40426
🇫🇷Bron, France
Aie001 40364
🇫🇷Lille, France
Aie001 40132
🇫🇷Nice, France
Aie001 40019
🇫🇷Paris, France
Aie001 40515
🇩🇪Berlin, Germany
Aie001 40567
🇮🇹Roma, Italy
Aie001 40249
🇩🇪Kiel, Germany
Aie001 40695
🇮🇹Pavia, Italy
Aie001 40267
🇪🇸Barcelona, Spain
Aie001 40341
🇪🇸Málaga, Spain
Aie001 40168
🇬🇧Nottingham, United Kingdom
Aie001 40163
🇬🇧Oxford, United Kingdom
Aie001 40264
🇳🇱Rotterdam, Netherlands
Aie001 40546
🇫🇷Nancy, France
Aie001 40286
🇫🇷Toulouse Cedex, France
Aie001 50104
🇺🇸Rochester, Minnesota, United States
Aie001 50101
🇺🇸Aurora, Colorado, United States
Aie001 50243
🇺🇸Boston, Massachusetts, United States
Aie001 50047
🇺🇸Boston, Massachusetts, United States
Aie001 50311
🇺🇸Cleveland, Ohio, United States
Aie001 50304
🇺🇸Dallas, Texas, United States