Clinical trial NCT04875975: A Study to Test the Efficacy, Safety, and Pharmacokinetics of Rozanolixizumab in Adult Study Participants With Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis
Keywords: Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis
Phase 2
Rozanolixizumab
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2021-05-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Seizure Free Study Participants at the End of the Treatment
timeFrame: From Baseline until the end of the Treatment (Week 25)
Secondary outcomes:
measure: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score at the End of the Treatment
timeFrame: From Baseline to Week 5, 13, 21 and 25
measure: Percentage of Participants With a Favorable Outcome in the Modified Rankin Scale (mRS) During the Treatment
timeFrame: From Baseline until the end of the Treatment (Week 25)
measure: Number of Participants Who Required Rescue Medication Due to an Absence or Loss of Clinical Benefit During the Treatment
timeFrame: From Baseline until the end of the Treatment (Week 25)
measure: Time to First Occurrence of Seizure Freedom During the Treatment
timeFrame: From Baseline until the end of the Treatment (Week 25)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Baseline until the End of Study (Week 32)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Aie001 50101
state: Colorado
city: Jacksonville
country: United States
facility: Aie001 50342
state: Florida
city: Boston
country: United States
facility: Aie001 50243
state: Massachusetts
city: Boston
country: United States
facility: Aie001 50047
state: Massachusetts
city: Rochester
country: United States
facility: Aie001 50104
state: Minnesota
city: New York
country: United States
facility: Aie001 50298
state: New York
city: Winston-Salem
country: United States
facility: Aie001 50090
state: North Carolina
city: Cleveland
country: United States
facility: Aie001 50311
state: Ohio
city: Dallas
country: United States
facility: Aie001 50304
state: Texas
city: Melbourne
country: Australia
facility: Aie001 30027
city: Bruxelles
country: Belgium
facility: Aie001 40123
city: Bordeaux
country: France
facility: Aie001 40129
city: Bron
country: France
facility: Aie001 40426
city: Lille
country: France
facility: Aie001 40364
city: Nancy
country: France
facility: Aie001 40546
city: Nice
country: France
facility: Aie001 40132
city: Paris
country: France
facility: Aie001 40019
city: Toulouse Cedex
country: France
facility: Aie001 40286
city: Berlin
country: Germany
facility: Aie001 40515
city: Kiel
country: Germany
facility: Aie001 40249
city: Pavia
country: Italy
facility: Aie001 40695
city: Roma
country: Italy
facility: Aie001 40567
city: Rotterdam
country: Netherlands
facility: Aie001 40264
city: Barcelona
country: Spain
facility: Aie001 40267
city: Málaga
country: Spain
facility: Aie001 40341
city: Nottingham
country: United Kingdom
facility: Aie001 40168
city: Oxford
country: United Kingdom
facility: Aie001 40163
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: