A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients with NMDAR or LGI1 mediated autoimmune Encephalitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

30 Nov 2022 → ongoing

Decision date (initial)

2024-09-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-504226-18-00

EudraCT number

2021-002395-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Safety

Part 1: To evaluate the efficacy of satralizumab compared with placebo on degree of disability and clinical severity, as measured by the proportion of participants with 1-point improvement in the Modified Rankin Scale (mRS) and no use of rescue therapy at Week 24 (NMDAR AIE cohort) and at week 52 (LGI1 AIE cohort)
Part 2: To evaluate the long-term safety and tolerability of satralizumab

Secondary objectives 2

1. To evaluate the efficacy of satralizumab compared with placebo based on NMDAR AIE cohort: Time to Modified Rankin Scale (mRS score) improvement without the use of rescue therapy, time to rescue therapy, proportion of participants with sustained seizure cessation (as defined by by 4 consecutive weeks of no seizures maintained until week 24 and no use of rescue therapy), change from baseline in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score, Montreal Overall Cognitive Assessment (MoCA) total score, , and mRS score; all at week 24 LGI1 AIE cohort: time to mRS score improvement ≥ 1 from baseline without use of rescue therapy, time to rescue therapy, 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, change in CASE score from baseline at Week 52, MoCA total score at Week 52 and Rey Auditory Verbal Learning Test (RAVLT) score at Week 52
2. To evaluate the safety of satralizumab compared with placebo

Conditions and MedDRA coding

NMDAR or LGI1 mediated autoimmune Encephalitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Reasonable exclusion of tumor or malignancy before baseline visit (randomization)
2. Onset of autoimmune encephalitis (AIE) symptoms <=9 months before randomization
3. Meet the definition of "New Onset" or "Incomplete Responder" AIE
4. Diagnosis of probable or definite NMDAR encephalitis
5. Diagnosis of LGI1 encephalitis

Exclusion criteria 6

1. Any untreated teratoma or thymoma at baseline visit (randomization)
2. History of carcinoma or malignancy, unless deemed cured by adequate treatment with no evidence of recurrence for >=5 years before screening
3. 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
4. Historically known positivity to an intracellular antigen with high cancer association or GAD65
5. Historically known positivity to any cell surface neuronal antibodies other than NMDAR and LGI1, in the absence of NMDAR and LGI1 antibody positivity
6. Confirmed paraneoplastic encephalitis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. NMDAR AIE cohort: Proportion of participants with mRS score improvement >=1 from baseline and no use of rescue therapy at Week 24
2. 2. LGI1 AIE cohort: Proportion of participants with mRS score improvement >=1 from baseline and no use of rescue therapy at week 52

Secondary endpoints 14

1. 1. NMDAR AIE cohort: Time to mRS score improvement >=1 from baseline without use of rescue therapy
2. 2. NMDAR AIE cohort: Time to rescue therapy
3. 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
4. 4. NMDAR AIE cohort: Change in CASE score from baseline at Week 24
5. 5. NMDAR AIE cohort: MOCA total score at Week 24
6. 6 . NMDAR AIE cohort: mRS score at Week 24 (as measured on a 7-point scale
7. 7. LGI1 AIE cohort: Time to mRS score improvement >=1 from baseline without use of rescue therapy
8. 8. LGI1 AIE cohort: Time to rescue therapy
9. 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
10. 10. LGI1 AIE cohort: Change in CASE score from baseline at Week 52
11. 11. LGI1 AIE cohort: MoCA total score at Week 52
12. 12. LGI1 AIE cohort: RAVLT score at Week 52
13. 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
14. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

8 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 3 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 161 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications