Clinical trial NCT06744920: A Study to Investigate the Efficacy, Safety and Tolerability of Remibrutinib Versus Placebo in Adult Patients With Generalized Myasthenia Gravis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Generalized Myasthenia Gravis
Keywords: Myasthenia Gravis
gMG
Generalized Myasthenia Gravis
LOU064
Remibrutinib
placebo-controlled
double-blind
phase III
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-12-20
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to evaluate the efficacy, safety and tolerability of Remibrutinib versus placebo in adult patients with Generalized Myasthenia Gravis who are on stable, standard-of-care (SOC) treatment.

Detailed description: This study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate the efficacy, safety and tolerability of remibrutinib in gMG patients who are on stable SOC treatment. Approximately 180 eligible participants will be randomized in a ratio of 1:1, to receive either remibrutinib or matching placebo.

The study consists of a Core Part (6-months double-blind treatment) and an Extension Part (up to 60-month open-label treatment).

Eligibility criteria: Inclusion Criteria:

* Adult patients with gMG (age 18-75 years)
* Confirmed diagnosis of Myasthenia Gravis Foundation of America (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
* Documented evidence of positive serologic testing for AChR+ antibody or MuSK+ antibody at screening, OR seronegative for both AChR and MuSK antibodies at screening
* Baseline MG-ADL score ≥ 6 with ≥ 50% of the total score due to non ocular symptoms
* Participants who have been on a stable dose of standard-of-care treatment as specified in the protocol
* 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:

* 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
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of study treatment

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: Change from baseline to Month 6 in Quantitative Myasthenia Gravis (QMG) total score
timeFrame: Baseline to Month 6
measure: 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
timeFrame: Baseline to Month 6
measure: Proportion of participants with ≥ 3 points reduction from baseline to Month 6 of Myasthenia Gravis Activity of Daily Living (MG-ADL) scale total score without rescue medication and/or strongly confounding prohibited medication
timeFrame: Baseline to Month 6
measure: Proportion of participants achieving Minimal Symptom Expression (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
timeFrame: Month 6
measure: Change from baseline to Month 6 in Myasthenia Gravis Composite score (MGC) total score
timeFrame: Baseline to Month 6
measure: Change from baseline to Month 6 in revised Myasthenia Gravis Quality of Life Questionnaire (MG-QOL15r) survey score
timeFrame: Baseline to Month 6
measure: Incidence of adverse events
timeFrame: Baseline to Month 6
measure: Proportion of time during which participants showed a reduction of ≥ 2 points in MG-ADL total score, that was maintained up to Month 6
timeFrame: Baseline to Month 6
measure: Proportion of early MG-ADL responders during treatment (early responders with first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4）
timeFrame: Baseline to week 4
measure: Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L)
timeFrame: Baseline to Month 6
measure: Proportion of participants achieving a reduction from baseline of ≥ 3 points in MGC total score at Month 6
timeFrame: Baseline to Month 6
measure: Change from baseline in MG-ADL total score
timeFrame: Baseline to Month 66
measure: Proportion of participants achieving a reduction from core part in oral corticosteroids (OCS) dose till the end of extension part
timeFrame: Baseline to month 66
measure: Incidence of adverse events
timeFrame: Month 7 to month 66
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Neuromuscular Research Center
state: Arizona
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Orange
country: United States
facility: Univ Cali Irvine ALS Neuromuscular
state: California
city: Boca Raton
country: United States
facility: SFM Clinical Research LLC
state: Florida
city: Homestead
country: United States
facility: Homestead Assoc In Research Inc
state: Florida
city: Orlando
country: United States
facility: Neurological Services of Orlando PA
state: Florida
city: Buffalo
country: United States
facility: Dent Neurological Institute
state: New York
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Seattle
country: United States
facility: University of WA Division of Cardio
state: Washington
city: Kogarah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
Study officials:
References: