A randomized, double-blind, placebo-controlled phase III study to evaluate the efficacy, safety, and tolerability of remibrutinib in patients with generalized Myasthenia Gravis, followed by an open-label extension phase.

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

11 Jun 2025 → ongoing

Decision date (initial)

2025-05-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-510026-32-00

ClinicalTrials.gov

NCT06744920

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Others, Pharmacodynamic, Pharmacoeconomic, Efficacy, Pharmacogenetic

To demonstrate efficacy of remibrutinib compared to placebo in patients with gMG in reducing the total score of the Myasthenia Gravis Activity of Daily Living (MG-ADL) scale at 6 months (Day 180) of treatment

Secondary objectives 11

1. To assess whether remibrutinib is superior to placebo in patients with gMG in reducing Quantitative MG (QMG) total score at 6 months of treatment
2. To assess whether remibrutinib is superior to placebo in patients with gMG on the proportion of study participants achieving a reduction from baseline to Month 6 of QMG total score ≥ 5 points without rescue medication and/or strongly confounding prohibited medication
3. To assess whether remibrutinib is superior to placebo in patients with gMG on the proportion of study participants achieving a reduction from baseline to Month 6 of MG-ADL total score ≥ 3 points without rescue medication and/or strongly confounding prohibited medication
4. To assess whether remibrutinib is superior to placebo in patients with gMG in achieving Minimal Symptom Expression (MSE) at Month 6, defined as an MG-ADL of 0 or 1 at Month 6 without rescue therapy and/or strongly confounding prohibited medication
5. To assess whether remibrutinib is superior to placebo in patients with gMG in reducing Myasthenia Gravis Composite (MGC) total score at Month 6 of treatment
6. To assess whether remibrutinib is superior to placebo in patients with gMG in reducing MG-QOL15r survey score at Month 6 of treatment
7. To evaluate the safety and tolerability of remibrutinib compared to placebo in patients with gMG
8. To evaluate the efficacy of remibrutinib compared to placebo in patients with gMG on other efficacy endpoints
9. To assess long-term efficacy of remibrutinib in patients with gMG during the Extension Part
10. To assess long-term effect of remibrutinib in patients with gMG on the proportion of study participants achieving a reduction from Core Part in oral corticosteroids (OCS) dose till the end of Extension Part
11. To assess long-term safety and tolerability of remibrutinib in patients with gMG

Conditions and MedDRA coding

Generalized Myasthenia Gravis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adult patients with gMG (age 18-85 years)
2. Confirmed diagnosis of MGFA Class II-IV gMG at screening and likely not in need of a respirator for the duration of the study, as judged by the Investigator.
3. Baseline MG-ADL score ≥6, with ≥50% of the total score due to non-ocular symptoms
4. Able to safely swallow the study medication according to investigator clinical judgement based on a bedside swallowing test or another formal swallowing test in line with local practice, both at Screening and Baseline

Exclusion criteria 2

1. Prior to baseline have been treated with intravenous immunoglobulins or plasma exchange (IVIg/PLEX) in the past month, with rituximab in the past 6 months, eculizumab in the past 2 months, ravulizumab or other complement inhibitors in the past 3 months, efgartigimod or other anti-FcRn therapies in the past 3 months, or had a thymectomy in the past 6 months or a planned thymectomy during the trial period
2. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score

Secondary endpoints 11

1. Change from baseline to Month 6 in Quantitative MG (QMG) total score
2. Proportion of participants with ≥ 5 points reduction from baseline to Month 6 of QMG total score without rescue medication and/or strongly confounding prohibited medication
3. Proportion of participants with ≥ 3 points reduction from baseline to Month 6 of MG-ADL total score without rescue medication and/or strongly confounding prohibited medication
4. Proportion of participants achieving MSE at Month 6, defined as MG-ADL score of 0 or 1 at Month 6 without rescue therapy and/or strongly confounding prohibited medication
5. Change from baseline to Month 6 in MGC total score
6. Change from baseline to Month 6 in revised MG Quality of Life Questionnaire (MG-QOL15r) survey score
7. Incidence of adverse events and changes in clinical laboratory values, vital signs, and electrocardiograms, Columbia Suicide Severity Rating
8. Proportion of time during which participants showed a reduction from baseline of ≥ 2 points in MG-ADL score that was maintained up to Month 6
9. Proportion of early MG-ADL responders during treatment (early responders with first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4）
10. Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L)
11. Proportion of participants achieving a reduction of ≥ 3 points from baseline to Month 6 in MGC total score.

Investigational products

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

Test 1

Placebo 1

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 14

Locations

8 EU/EEA countries · 43 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 91 files

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

Application history

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