Efficacy and safety of remibrutinib after switching from ocrelizumab in participants living with relapsing multiple sclerosis, followed by open-label treatment with remibrutinib.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

6 Oct 2025 → ongoing

Decision date (initial)

2025-08-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509275-17-00

ClinicalTrials.gov

NCT06846281

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To demonstrate that remibrutinib is non-inferior to ocrelizumab in controlling inflammatory activity on magnetic resonance imaging (MRI) after switching from ocrelizumab.

Secondary objectives 4

1. To assess whether remibrutinib is non-inferior to ocrelizumab in controlling disease-activity free status after switching from ocrelizumab.
2. To assess the safety and tolerability of remibrutinib after switching from ocrelizumab and compared to ocrelizumab.
3. Extension Part: To assess long-term safety, and tolerability in participants treated with remibrutinib after ocrelizumab.
4. Extension Part: To assess long-term efficacy parameters in participants treated with remibrutinib after ocrelizumab.

Conditions and MedDRA coding

Relapsing multiple sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed informed consent obtained prior to any assessment performed (confirm at Screening Visit).
2. Male or female aged 40 (Commercially confidential information) at Screening.
3. Diagnosis of RMS according to the revised 2017 McDonald criteria at Screening.
4. EDSS score of (Commercially confidential information) at Screening and randomization.
5. Treated with ocrelizumab according to routine clinical practice and at standard doses (Commercially confidential information).
6. Neurologically stable within 30 days prior to Screening and randomization (including no MS relapse in this period).
7. Suitable to be switched to remibrutinib based on physician judgement or patient preference.

Exclusion criteria 15

1. Diagnosis of primary progressive multiple sclerosis (PPMS) according to the revised 2017 McDonald criteria at Screening.
2. Resting QT interval corrected by Fridericia’s formula (QTcF) ≥ (Commercially confidential information) msec (male) or ≥ (Commercially confidential information) msec (female) at pre-treatment as per central ECG reading at Screening visit.
3. Use of exclusionary medication prior to Screening/randomization (as defined in the protocol).
4. Use of other investigational drugs within 5 half-lives of Screening; or within 30 days (e.g. small molecules); or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics); whichever is longer; or longer if required by local regulations.
5. Significant (Commercially confidential information) at Screening.
6. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception and do not donate eggs while taking study treatment and for (Commercially confidential information) after stopping ocrelizumab.
7. History of life-threatening infusion or injection reaction related to ocrelizumab, such as acute hypersensitivity or acute respiratory distress syndrome.
8. History of clinically significant CNS disease (e.g., stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS at Screening.
9. Participants with history of confirmed progressive multifocal leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to randomization.
10. Participants who have had a splenectomy.
11. Active clinically significant systemic bacterial, viral, parasitic or fungal infections in the judgement of the investigator prior to randomization (e.g. infections requiring hospitalization or i.v. antibiotics)
12. Active, chronic disease of the immune system (including stable disease treated with immune therapy, e.g. leflunomide, methotrexate) other than MS (e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder.
13. Participants with a known immunodeficiency syndrome (acquired immunodeficiency syndrome (AIDS), hereditary immune deficiency, or drug induced immune deficiency other than those caused by anti-CD20 therapy), or tested positive for human immunodeficiency virus (HIV) antibody, at Screening.
14. Participants at risk of developing or having reactivation of hepatitis: Positive results at Screening for serological markers for hepatitis (H) A, B, C, and E indicating acute or chronic infection: - anti-HA Immunoglobulin (Ig) M (IgM) - HB surface Antigen (HBs Ag) and/or anti-HBc IgM and/or HB virus deoxyribonucleic acid (DNA) - anti-HBc positive - anti-HC IgG (if positive IgG, HC Virus (HCV)-RNA Polymerase Chain Reaction (PCR) will be performed and if negative, participant can be randomized) - anti-HE IgM positive (regardless of IgG status)
15. Participants with any of the following abnormal hematology laboratory values at Screening: - Hemoglobin: (Commercially confidential information) - Platelets: (Commercially confidential information) - Absolute lymphocyte count (Commercially confidential information) - White blood cells: (Commercially confidential information) - Neutrophils: (Commercially confidential information) - (Commercially confidential information)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of new or enlarging T2 lesions (AR-NELT2) on MRI at Month 24 (relative to baseline MRI scan).

Secondary endpoints 4

1. Participants with no evidence of disease activity-3 (NEDA-3), as assessed by absence of confirmed MS relapses, 6-month confirmed disability progression (6mCDP) and new/enlarging T2 lesions on MRI between baseline and Month 24.
2. Adverse events, laboratory data, vital signs, electrocardiograms (ECGs), (Commercially confidential information).
3. Extension Part: Adverse events, laboratory data, vital signs, electrocardiogram (ECG), (Commercially confidential information).
4. Extension Part: - Annualized rate of new or enlarging T2 lesions on MRI - Participants with NEDA-3.

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 12

Locations

10 EU/EEA countries · 62 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 81 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