A study to test the efficacy, safety, and pharmacokinetics of rozanolixizumab in adult study participants with Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis
- Conditions
- Therapeutic area: Diseases [C] - Immune System Diseases [C20]eucine-Rich Glioma Inactivated 1 Autoimmune EncephalitisMedDRA version: 20.0Level: PTClassification code 10072378Term: Encephalitis autoimmuneSystem Organ Class: 10029205 - Nervous system disorders
- Registration Number
- EUCTR2019-004778-25-FR
- Lead Sponsor
- CB Biopharma SR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 68
-Study participant must be =18 to =89 years of age, at the time of signing the informed consent
-Study participant must be seropositive for leucine-rich glioma inactivated 1 (LGI1) antibody measured by LGI1 serum autoantibody cell-binding assay
-Study participant must have faciobrachial dystonic seizures (FBDS) and/or other partial [focal] seizures with or without secondary generalization (=2 seizures/week) during the Screening Period, or have experienced such seizures that stopped as a result of intravenous
methylprednisolone (IVMP) initiation
-Study participant is currently considered for treatment with IVMP by the investigator or has initiated IVMP treatment at a dose of 500 to 1000 mg/day within 14 days prior to randomization. If the study participant has initiated a steroid taper, the study participant cannot be receiving an
oral steroid dose lower than 60 mg/day when randomized
-Study participant with onset of disease between 0 to 12 months prior to Screening
-Study participant weighs at least 35 kg (for males and females) at Screening
-A male participant must agree to use contraception during the treatment period and for at least 90 days after the final dose of study treatment and refrain from donating sperm during this period
-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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
-Study participant has a known hypersensitivity to any components of the study medication or any other anti-neonatal Fc receptor (FcRn) medications. This includes a known history of hyperprolinemia, since L-proline is a constituent of the rozanolixizumab formulation
-Study participant has a confirmed prior diagnosis of epilepsy that is unrelated to LGI1 autoimmune encephalitis (AIE)
-Study participant has active neoplastic disease or history of neoplastic disease within 5 years of study entry (except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix which has been definitively treated with standard of care approaches)
-Study participant has 12-lead electrocardiogram (ECG) with findings considered clinically significant upon medical review
-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 any of the following active gastrointestinal (GI) disorders: inflammatory bowel disease, GI ulceration, or diverticulitis
-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 been treated with prohibited immunosuppressants, biologics, and other therapies
-Study participant has received a live vaccination within 8 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 >2x upper limit of normal (ULN)
-Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 %)
-Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
-For randomized study participants with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin but <1.5xULN, a Baseline diagnosis and/or the cause of any clinically meaningful elevation will have to be understood and recorded in the electronic case report form (eCRF)
-If study participant has >ULN for ALT, AST, or ALP that does not meet the exclusion limit at Screening, the tests should be repeated, if possible, prior to dosing to ensure there was no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the study participants will have to be discussed with the medical monitor
-Tests that result in ALT, AST, or ALP up to 25 % above the exclusion limit (>2xULN) will have to be repeated once for confirmation. This includes rescreening
-Study participant has an IgG level =5.5 g/L at the Screening Visit
-Study participant has absolute neutrophil count <1500 cells/mm^3 at the Screening Visit
-Participant has QT interval corrected for heart rate using Fridericia’s formula (QTcF) >450 msec (for male participants) or QTcF >470 msec (for female participants) or QTcF >480 msec in participants with bundle branch block
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Assess the efficacy of rozanolixizumab as measured by seizure freedom;Secondary Objective: -Assess the efficacy of rozanolixizumab as measured by a change in cognitive function<br>-Assess the efficacy of rozanolixizumab as measured by use of rescue medication<br>-Assess the efficacy of rozanolixizumab as measured by the onset of seizure freedom<br>-Assess the safety and tolerability of rozanolixizumab ;Primary end point(s): Proportion of seizure free study participants at the end of the Treatment Period;Timepoint(s) of evaluation of this end point: From Baseline until the end of Treatment Period (Week 25)
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Change from Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score at the end of the Treatment Period<br>2. Proportion of participants who required rescue medication due to an absence or loss of clinical benefit during the Treatment Period<br>3. Time to first occurrence of seizure freedom during the Treatment Period<br>4. Incidence of Treatment-Emergent Adverse Events (TEAEs);Timepoint(s) of evaluation of this end point: 1-3: From Baseline until the end of the Treatment Period (Week 25)<br>4: From Baseline until the End of Study Visit (Week 32)