E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leucine-Rich Glioma Inactivated 1 Autoimmune Encephalitis |
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E.1.1.1 | Medical condition in easily understood language |
Autoimmune encephalitis comprises a group of immune system-mediated conditions whereby the individual's immune cells erroneously target healthy cells in the nervous system including brain cells. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072378 |
E.1.2 | Term | Encephalitis autoimmune |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess the efficacy of rozanolixizumab as measured by seizure freedom |
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E.2.2 | Secondary objectives of the trial |
-Assess the efficacy of rozanolixizumab as measured by a change in cognitive function -To assess the efficacy of rozanolixizumab on study participants' overall disability -Assess the efficacy of rozanolixizumab as measured by use of rescue medication -Assess the efficacy of rozanolixizumab as measured by the onset of seizure freedom -Assess the safety and tolerability of rozanolixizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 be receiving an oral steroid dose lower than 40 mg/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
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E.4 | Principal exclusion criteria |
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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of seizure free study participants at the end of the Treatment Period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Baseline until the end of Treatment Period (Week 25) |
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E.5.2 | 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 2. Proportion of participants with a favorable outcome in the Modified Rankin Scale (mRS) during the Treatment Period 3. Proportion of participants who required rescue medication due to an absence or loss of clinical benefit during the Treatment Period 4. Time to first occurrence of seizure freedom during the Treatment Period 5. Incidence of Treatment-Emergent Adverse Events (TEAEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4: From Baseline until the end of the Treatment Period (Week 25) 5: From Baseline until the End of Study Visit (Week 32) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability and Immunogenicity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ukraine |
Australia |
Korea, Republic of |
Turkey |
United Kingdom |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Netherlands |
Portugal |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 24 |