Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
116
Countries
2
Sites
2
anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis)
The primary objective is to determine the difference in disability (as measured by the mRS scale) of patients with anti-NMDAR encephalitis 16 weeks after treatment with inebilizumab compared to treatment with placebo (in both groups in addition to standard care).
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20], Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 10 Dec 2024 → ongoing
- Decision date (initial)
- 2023-10-10
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2023-504686-23-00
- ClinicalTrials.gov
- NCT04372615
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Therapy, Efficacy
The primary objective is to determine the difference in disability (as measured by the mRS scale) of patients with anti-NMDAR encephalitis 16 weeks after treatment with inebilizumab compared to treatment with placebo (in both groups in addition to standard care).
Secondary objectives 1
- To evaluate the effect of inebilizumab on other measures of disease activity
Conditions and MedDRA coding
anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10072379 | Anti-NMDA receptor encephalitis | 10029205 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening period up to 14 days from signing informed consent
|
Not Applicable | None | ||
| 2 | Randomized control period from randomization until 24 weeks after randomization
|
Randomised Controlled | Double | [{"id":157160,"code":2,"name":"Investigator"},{"id":157157,"code":5,"name":"Carer"},{"id":157158,"code":3,"name":"Monitor"},{"id":157161,"code":4,"name":"Analyst"},{"id":157159,"code":1,"name":"Subject"}] | Inebilizumab group: Inebilizumab 300 mg intravenous (IV) Placebo group: Matching placebo IV |
| 3 | Follow up phase from 24 weeks after randomization until 96 weeks, or until 24 weeks after the last participant is randomized
|
Not Applicable | None |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2020-000417-33 | A Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Study of Inebilizumab Efficacy and Safety in IgG4 Related Disease, 3. fázisú, randomizált, kettős vak, multicentrikus, placebo-kontrollos vizsgálat az inebilizumab hatásosságának és biztonságosságának értékelésére IgG4-asszociált betegségben szenvedőknél , Studio di fase 3, randomizzato, in doppio cieco, multicentrico, controllato con placebo, volto a valutare l’efficacia e la sicurezza di Inebilizumab nella malattia IgG4-correlata (Titolo breve: MITIGATE – Efficacia e sicurezza di inebilizumab nella malattia IgG4-correlata), Estudio fase 3, aleatorizado, doble ciego, multicéntrico y controlado con placebo para evaluar la eficacia y la seguridad de inebilizumab en enfermedades relacionadas con IgG4 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Diagnosis of NMDAR encephalitis, defined by a subacute onset of change in mental status consistent with autoimmune encephalitis AND a positive cell-based assay for NMDAR immunoglobulin G antibody in the cerebrospinal fluid confirmed in study-specified laboratories
- Willing to forego other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study
- mRS of ≥ 3 at the screening visit, indicating at least moderate disability
- Participant must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 30 days prior to randomization (Day 1). In addition, participants must have received EITHER IVIg, at dose range between 1.2 and 2 g/kg OR Plasma exchange or plasmapheresis, with a minimum of 5 treatments
Exclusion criteria 4
- Recurrence of previously treated NMDAR encephalitis within the last 5 years, or suspicion of symptomatic untreated NMDAR encephalitis of greater than 3 months duration at the time of screening
- Receipt of any biologic B cell-depleting therapy (e.g., rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) in the 6 months prior to screening
- Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the investigational product, interpretation of participant safety or study results, or would make participation in the study an unacceptable risk
- Receipt of any of the following within 3 months prior to randomization: Natalizumab (Tysabri (r)), Cyclosporine, Methotrexate, Mitoxantrone, Cyclophosphamide, Azathioprine, Mycophenolate mofetil
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Change in mRS at 16 weeks
- Inebilizumab safety, as measured by the number of treatment-emergent adverse events and treatment-emergent serious adverse events from randomization to 24 weeks
Secondary endpoints 7
- Time to mRS ≤ 2, corrected for baseline value, over 16 weeks
- CASE Score (linear mixed model), corrected from baseline value to Week 24 (Weeks 6 and 16)
- mRS at Week 6 as measured by proportional odds logistic regression/shift analysis
- Proportion of participants who meet the protocol-defined criteria for needing rescue therapy with cyclophosphamide at Week 6, as measured by logistic regression
- Cognitive outcome at Week 24 as measured by the total scaled score on the RBANS + total raw score on the TMT
- Clinician global impression of change (CGI-I) and Caregiver global impression of change (CaGI) over 24 weeks, as measured by ordinal repeated measures models
- Survival as measured by a Kaplan-Meier analysis
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Uplizna 100 mg concentrate for solution for infusion
PRD9656930 · Product
- Active substance
- Inebilizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 600 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AA47 — -
- Marketing authorisation
- EU/1/21/1602/001
- MA holder
- HORIZON THERAPEUTICS IRELAND DAC
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- Route of administration
- INTRAVENOUS
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 600 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 9
Privigen 100 mg/ml solution for infusion
PRD339229 · Product
- Active substance
- Human Normal Immunoglobulin
- Substance synonyms
- IMMUNOGLOBULIN HUMAN NORMAL
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2 mg/g milligram(s)/gram
- Max total dose
- 10 mg/g milligram(s)/gram
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- EU/1/08/446/006
- MA holder
- CSL BEHRING GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- 656
- Modified vs. Marketing Authorisation
- No
SUB08872MIG · Substance
- Active substance
- Methylprednisolone
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1000 mg milligram(s)
- Max total dose
- 11000 mg milligram(s)
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- 656
- Modified vs. Marketing Authorisation
- No
KIOVIG 100 mg/ml solution for infusion
PRD7734935 · Product
- Active substance
- Human Normal Immunoglobulin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2 mg/g milligram(s)/gram
- Max total dose
- 10 mg/g milligram(s)/gram
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- EU/1/05/329/006
- MA holder
- TAKEDA MANUFACTURING AUSTRIA AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- 656
- Modified vs. Marketing Authorisation
- No
Plangamma 50 mg/ml solución para perfusión
PRD1164862 · Product
- Active substance
- Human Normal Immunoglobulin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2 mg/g milligram(s)/gram
- Max total dose
- 10 mg/g milligram(s)/gram
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- 78149
- MA holder
- INSTITUTO GRIFOLS, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- 656
- Modified vs. Marketing Authorisation
- No
Flebogamma DIF 50 mg/ml solution for infusion
PRD3583068 · Product
- Active substance
- Human Normal Immunoglobulin (IV)
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2 mg/g milligram(s)/gram
- Max total dose
- 10 mg/g milligram(s)/gram
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- EU/1/07/404/001
- MA holder
- INSTITUTO GRIFOLS, S.A.
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- 656
- Modified vs. Marketing Authorisation
- No
SUB09611MIG · Substance
- Active substance
- Paracetamol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 1000 mg milligram(s)
- Max total dose
- 2000 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08872MIG · Substance
- Active substance
- Methylprednisolone
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07451MIG · Substance
- Active substance
- Cetirizine
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 750 mg/m2 milligram(s)/sq. meter
- Max total dose
- 20 g gram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- M.J. Titulaer
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- M.J. Titulaer
Locations
2 EU/EEA countries · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 18 | 1 |
| Spain | Ongoing, recruiting | 8 | 1 |
| Rest of world
United States
|
— | 90 | — |
Investigational sites
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Neurology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-12-10 | 2025-07-10 | |||
| Spain | 2025-02-14 | 2025-03-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-504686-23 SoC | 1 |
| Protocol (for publication) | D2 Protocol modification NSM-4 2023-504686-23 Clean redacted | 9.0 |
| Recruitment arrangements (for publication) | K1 Recruitment arrangements_2023-504686-23 | 1.1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF adults | 1.2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF legal representative | 1.2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC_Inebilizumab | 1 |
| Synopsis of the protocol (for publication) | D1 Protocol Synopsis_EN 2023-504686-23 | 2 |
| Synopsis of the protocol (for publication) | D1 Protocol Synopsis_ES 2023-504686-23 | 1 |
| Synopsis of the protocol (for publication) | D1 Protocol Synopsis_NL 2023-504686-23 | 2 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-27 | Netherlands | Acceptable 2023-10-10
|
2023-10-10 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-07-26 | Netherlands | Acceptable 2023-10-10
|
2024-07-26 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2024-09-24 | Netherlands | Acceptable 2023-10-10
|
2024-09-24 |
| 4 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-04-02 | Netherlands | Acceptable 2025-06-25
|
2025-06-25 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-11-13 | Netherlands | Acceptable 2025-06-25
|
2025-11-13 |