Clinical trial • Phase III • Neurology

satralizumab for Anti-NMDAR encephalitis | Anti-LGI1 encephalitis

Phase III trial of satralizumab for Anti-NMDAR encephalitis | Anti-LGI1 encephalitis.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Anti-NMDAR encephalitis | Anti-LGI1 encephalitis
Trial Stage
Phase III
Drug Modality
Monoclonal antibody
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
31-07-2024
First CTIS Authorization Date
06-09-2024

Trial design

Randomised, placebo (matching comparator); no dose or schedule specified in provided data-controlled Phase III trial in Austria, France, Netherlands and others.

Randomised
Yes
Comparator
Placebo (matching comparator); no dose or schedule specified in provided data
Biomarker Stratified
True, anti-NMDAR and anti-LGI1 antibody cohorts
Target Sample Size
134
Trial Duration For Participant
364

Eligibility

Recruits 134 paediatric patients.

Vulnerable Population
Vulnerable populations are included (isVulnerablePopulationSelected = true). Age-specific and caregiver documents are provided: infant, adolescent, and parent/caregiver consent forms and 'adult representative' forms are present (eg. 'L1_SISandICF_Infant', 'L1_ICF Main 12-16 years', 'WN43174_Asentimiento 12 a 17 anos', 'L1_SISandICF_Main_parents', 'L1_SISandICF_adult representative'). Consent is obtained from adult participants or from parent/legal guardian for minors; age-appropriate assent is documented for adolescents (assent forms for 12-17 / 12-16 / 15-17 present).

Inclusion criteria

  • {"criterion_text":"- Reasonable exclusion of tumor or malignancy before baseline visit (randomization)\n- Onset of autoimmune encephalitis (AIE) symptoms <=9 months before randomization\n- Meet the definition of \"New Onset\" or \"Incomplete Responder\" AIE\n- Diagnosis of probable or definite NMDAR encephalitis\n- Diagnosis of LGI1 encephalitis"}

Exclusion criteria

  • {"criterion_text":"- Any untreated teratoma or thymoma at baseline visit (randomization)\n- History of carcinoma or malignancy, unless deemed cured by adequate treatment with no evidence of recurrence for >=5 years before screening\n- For patients with NMDAR AIE, history of negative anti-NMDAR antibody in cerebrospinal fluid (CSF) using a cell-based assay within 9 months of symptom onset\n- Historically known positivity to an intracellular antigen with high cancer association or GAD65\n- Historically known positivity to any cell surface neuronal antibodies other than NMDAR and LGI1, in the absence of NMDAR and LGI1 antibody positivity\n- Confirmed paraneoplastic encephalitis"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. NMDAR AIE cohort: Proportion of participants with mRS score improvement >=1 from baseline and no use of rescue therapy at Week 24","definition_or_measurement_approach":"Proportion of participants with a ≥1-point improvement in the Modified Rankin Scale (mRS) from baseline and no use of rescue therapy assessed at Week 24 (NMDAR cohort)."}
  • {"endpoint_text":"- 2. LGI1 AIE cohort: Proportion of participants with mRS score improvement >=1 from baseline and no use of rescue therapy at week 52","definition_or_measurement_approach":"Proportion of participants with a ≥1-point improvement in the Modified Rankin Scale (mRS) from baseline and no use of rescue therapy assessed at Week 52 (LGI1 cohort)."}

Secondary endpoints

  • {"endpoint_text":"- 1. NMDAR AIE cohort: Time to mRS score improvement >=1 from baseline without use of rescue therapy","definition_or_measurement_approach":"Time from randomization to first occurrence of ≥1-point mRS improvement without subsequent use of rescue therapy (NMDAR cohort)."}
  • {"endpoint_text":"- 2. NMDAR AIE cohort: Time to rescue therapy","definition_or_measurement_approach":"Time from randomization to initiation of rescue therapy (NMDAR cohort)."}
  • {"endpoint_text":"- 3. NMDAR AIE cohort: Proportion of participants with sustained seizure cessation at Week 24, as defined by 4 consecutive weeks of no seizures maintained until Week 24, and no use of rescue therapy","definition_or_measurement_approach":"Proportion achieving sustained seizure cessation defined as 4 consecutive weeks with no seizures maintained through Week 24 and no rescue therapy use."}
  • {"endpoint_text":"- 4. NMDAR AIE cohort: Change in CASE score from baseline at Week 24","definition_or_measurement_approach":"Change from baseline in the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) at Week 24."}
  • {"endpoint_text":"- 5. NMDAR AIE cohort: MOCA total score at Week 24","definition_or_measurement_approach":"Montreal Cognitive Assessment (MoCA) total score measured at Week 24."}
  • {"endpoint_text":"- 6 . NMDAR AIE cohort: mRS score at Week 24 (as measured on a 7-point scale","definition_or_measurement_approach":"mRS score measured on a 7-point scale at Week 24 (NMDAR cohort)."}
  • {"endpoint_text":"- 7. LGI1 AIE cohort: Time to mRS score improvement >=1 from baseline without use of rescue therapy","definition_or_measurement_approach":"Time from randomization to first ≥1-point mRS improvement without rescue therapy (LGI1 cohort)."}
  • {"endpoint_text":"- 8. LGI1 AIE cohort: Time to rescue therapy","definition_or_measurement_approach":"Time from randomization to initiation of rescue therapy (LGI1 cohort)."}
  • {"endpoint_text":"- 9. LGI1 AIE cohort: Proportion of participants with sustained seizure cessation at Week 24, as defined by 4 consecutive weeks of no seizures maintained until Week 24, and no use of rescue therapy","definition_or_measurement_approach":"Proportion with sustained seizure cessation defined as 4 consecutive weeks without seizures maintained to Week 24 and no rescue therapy use (LGI1 cohort)."}
  • {"endpoint_text":"- 10. LGI1 AIE cohort: Change in CASE score from baseline at Week 52","definition_or_measurement_approach":"Change from baseline in CASE score at Week 52 (LGI1 cohort)."}
  • {"endpoint_text":"- 11. LGI1 AIE cohort: MoCA total score at Week 52","definition_or_measurement_approach":"MoCA total score measured at Week 52 (LGI1 cohort)."}
  • {"endpoint_text":"- 12. LGI1 AIE cohort: RAVLT score at Week 52","definition_or_measurement_approach":"Rey Auditory Verbal Learning Test (RAVLT) score measured at Week 52 (LGI1 cohort)."}
  • {"endpoint_text":"- 13. Incidence, seriousness, and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0","definition_or_measurement_approach":"Adverse events assessed for incidence, seriousness and severity; severity graded per NCI CTCAE v5.0."}
  • {"endpoint_text":"- 14 . Change from baseline in targeted vital signs, clinical laboratory test results, electrocardiogram (ECG) results, weight, height (<18 years only), and Columbia-Suicide Severity Rating Scale (C-SSRS)","definition_or_measurement_approach":"Change from baseline in selected vital signs, labs, ECG results, weight, height (for participants <18 years only) and C-SSRS assessments."}

Recruitment

Planned Sample Size
134
Recruitment Window Months
55
Consent Approach
Informed consent obtained from adult participants or from parent/legal guardian for minors. Age-appropriate assent is used for adolescents (assent documents for 12-16 / 12-17 / 15-17 years are included). Specific caregiver/parent information and consent forms and 'adult representative' forms are provided. Patient information and consent documents exist in multiple languages (English, French, Dutch, Polish, Spanish, German (de-at), Italian, Czech) as evidenced by multiple language versions of SIS/ICF and patient-facing documents.

Geography

Total Number Of Sites
23
Total Number Of Participants
47

Austria

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
08-09-2024
Processing Time Days
25
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Johannes Kepler University Linz
Department Name
University Clinic for Neurology
Contact Person Name
Gabriele Schwarz
Site Name
Medical University Of Vienna
Department Name
Department of Neurology
Contact Person Name
Paulus Stefan Rommer
Contact Person Email
neurostudien@meduniwien.ac.at

France

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
09-09-2024
Processing Time Days
26
Number Of Sites
4
Number Of Participants
7

Sites

Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Neurology department
Contact Person Name
Jean-Philippe CAMDESSANCHE
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Neuro-oncology department
Contact Person Name
Dimitri PSIMARAS
Contact Person Email
dimitri.psimaras@aphp.fr
Site Name
Hospices Civils De Lyon
Department Name
Neuro-oncology department
Contact Person Name
Jerome HONNORAT
Contact Person Email
jerome.honnorat@chu-lyon.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Neurology and clinical neurophysiology department
Contact Person Name
Coline DUWICQUET
Contact Person Email
c.duwicquet@chu-tours.fr

Netherlands

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
10-09-2024
Processing Time Days
27
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Neurologie
Contact Person Name
Juna de Vries
Contact Person Email
trials.neurologie@erasmusmc.nl

Poland

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
05-10-2024
Processing Time Days
52
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
Department Name
Oddział Kliniczny Neurologii
Contact Person Name
Agnieszka Słowik
Contact Person Email
neurologia@su.krakow.pl
Site Name
Samodzielny Publiczny Szpital Kliniczny Nr 1 Im.Prof.Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego W Katowicach
Department Name
Oddział Neurologiczny
Contact Person Name
Monika Adamczyk-Sowa
Contact Person Email
sekretariat@szpital.zabrze.pl
Site Name
Instytut Psychiatrii I Neurologii
Department Name
II Klinika Neurologiczna
Contact Person Name
Iwona Kurkowska-Jastrzębska
Contact Person Email
neuro2@ipin.edu.pl

Denmark

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
06-09-2024
Processing Time Days
23
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Odense University Hospital
Department Name
Neurologisk Afdeling N
Contact Person Name
Morten Blaabjerg
Contact Person Email
Morten.Blaabjerg1@rsyd.dk

Czechia

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
09-09-2024
Processing Time Days
26
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Fakultni Nemocnice Hradec Kralove
Department Name
Neurologická klinika
Contact Person Name
Zbyšek Pavelek
Contact Person Email
zbysekpavelek@fnhk.cz
Site Name
Fakultni Nemocnice V Motole
Department Name
Neurologická klinika 2.LF UK a FN Motol
Contact Person Name
Martin Elišák
Contact Person Email
studie@fnmotol.cz

Spain

Earliest CTIS Part Ii Submission Date
30-06-2025
Latest Decision Or Authorization Date
20-08-2025
Processing Time Days
51
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Hospital Universitario Regional De Malaga
Department Name
Neurology
Contact Person Name
Pedro Serrano Castro
Contact Person Email
pedro.serrano.c@gmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Neurology
Contact Person Name
Marisa Martinez Ginés
Contact Person Email
marisamgines@hotmail.com
Site Name
Hospital Alvaro Cunqueiro
Department Name
Neurology
Contact Person Name
Inés María González Suárez

Italy

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
17-09-2024
Processing Time Days
34
Number Of Sites
7
Number Of Participants
17

Sites

Site Name
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Department Name
U.O.C. di Neurologia
Contact Person Name
Giuseppe Salemi
Contact Person Email
giuseppe.salemi@unipa.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
Contact Person Name
Massimo Filippi
Contact Person Email
filippi.massimo@hsr.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
U.O. Clinica Neurologica
Contact Person Name
Federico Massa
Contact Person Email
federico.massa@hsanmartino.it
Site Name
IRCCS Foundation Istituto Neurologico Carlo Besta
Department Name
U.O.C Neurologia 7, Epilettologia Clinica e Sperimentale
Contact Person Name
Francesco Deleo
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Neuroscienze, Scienze Riproduttive e Odontostomatologiche
Contact Person Name
Roberta Lanzillo
Contact Person Email
roberta.lanzillo@unina.it
Site Name
Fondazione Istituto Neurologico Nazionale Casimiro Mondino
Department Name
Neuroimmunologia
Contact Person Name
Matteo Gastaldi
Contact Person Email
matteo.gastaldi@mondino.it
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
Neurologia I
Contact Person Name
Antonio Gallo
Contact Person Email
antonio.gallo@unicampania.it

Sponsor

Primary sponsor

Full Name
F. Hoffmann-La Roche AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
IQVIA Limited
Responsibilities
Monitoring
Name
Signant Health Global LLC
Responsibilities
Other Third Party Duty
Name
Biotrial
Responsibilities
Other Third Party Duty
Name
Labcorp Central Laboratory Services SARL
Name
Parexel Bioanalytical Services Division
Name
SRL Inc.
Name
Greenphire LLC
Responsibilities
Other Third Party Duty
Name
Almac Clinical Technologies LLC

Third parties

  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Monitoring","organisation_type":"Pharmaceutical company"}
  • {"country":"Japan","full_name":"SRL Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Other Third Party Duty","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Biotrial","duties_or_roles":"Other Third Party Duty","organisation_type":"Pharmaceutical company"}
  • {"country":"South Africa","full_name":"Parexel Bioanalytical Services Division","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Other Third Party Duty","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Satralizumab
Active Substance
satralizumab
Modality
Monoclonal antibody
Authorisation Status
Marketing authorisation present for product PRD9016776: EU/1/21/1559/001 (other test product entry appears to be investigational/unlicensed)
Orphan Designation
Yes
Investigational Product Name
Satralizumab (sponsor product code RO 533-3787/F01-06)
Active Substance
satralizumab
Modality
Monoclonal antibody
Authorisation Status
Investigational / no marketing authorisation number listed for product PRD10948861
Investigational Product Name
Placebo
Modality
Other

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