A Study to Investigate the Efficacy, Safety and Tolerability of Remibrutinib Versus Placebo in Adult Patients With Generalized Myasthenia Gravis
PHASE3ACTIVE_NOT_RECRUITING
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.
Study details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06744920
Intervention or treatment
DRUG: Remibrutinib (Blinded)
OTHER: Placebo
DRUG: Remibrutinib (Open Label)
Conditions
- Generalized Myasthenia Gravis
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Research sites nearby
Closest Location:
Novartis Investigative Site
Select from list below to view details:
Novartis Investigative Site
Kogarah, New South Wales, Australia
Novartis Investigative Site
Fitzroy, Victoria, Australia
Novartis Investigative Site
Southport, Australia
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Who is running the clinical trial?
NP
Novartis Pharmaceuticals
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Remibrutinib arm
| Drug: Remibrutinib (Blinded), Drug: Remibrutinib (Open Label) |
PLACEBO_COMPARATOR: Placebo arm
| Other: Placebo, Drug: Remibrutinib (Open Label) |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score | The MG-ADL is a categorical scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function (total score 0 to 24). | Baseline to Month 6 |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline to Month 6 in Quantitative Myasthenia Gravis (QMG) total score | The Quantitative Myasthenia Gravis (QMG) Score is a 13-item direct physician assessment scoring system that quantifies disease severity, based on impairments of body functions and structures. The total QMG score ranges from 0 to 39, where higher scores indicated greater disease severity. The QMG score is composed of the following items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item) and respiratory (1 item). | Baseline to Month 6 |
| 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 | The Quantitative Myasthenia Gravis (QMG) Score is a 13-item direct physician assessment scoring system that quantifies disease severity, based on impairments of body functions and structures. The total QMG score ranges from 0 to 39, where higher scores indicated greater disease severity. The QMG score is composed of the following items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item) and respiratory (1 item). | Baseline to Month 6 |
| 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 | The MG-ADL is a categorical scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function (total score 0 to 24). | Baseline to Month 6 |
| 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 | The MG-ADL is a categorical scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function (total score 0 to 24). | Month 6 |
| Change from baseline to Month 6 in Myasthenia Gravis Composite score (MGC) total score | The MGC is a 10-item instrument that measures the symptoms and signs of MG based on physician examination and patient history. Items relate to ptosis, double vision, eye closure, talking, chewing, swallowing, breathing, neck flexion, shoulder abduction, and hip flexion. Each item is scored on an ordinal scale with 4 possible categories and weighted. The total score ranges from 0 to 50, where higher scores indicating more severe impairments. | Baseline to Month 6 |
| Change from baseline to Month 6 in revised Myasthenia Gravis Quality of Life Questionnaire (MG-QOL15r) survey score | The revised MG-QoL15 is a 15-item health related quality of life questionnaire completed by participants, designed to measure quality of life in gMG. Items on the MG-QoL15 relate to physical, social, and psychological components and are scored from 0 (not at all) to 2 (very much). The cumulative scores range from 0 to 30, with higher scores representing worse quality of life and dissatisfaction with MG-related dysfunction. | Baseline to Month 6 |
| Incidence of adverse events | Incidence of adverse events including changes in clinical laboratory values, vital signs, electrocardiograms and suicidality results qualifying and reported as AEs. | Baseline to Month 6 |
| Proportion of time during which participants showed a reduction of ≥ 2 points in MG-ADL total score, that was maintained up to Month 6 | The MG-ADL is a categorical scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function (total score 0 to 24). | Baseline to Month 6 |
| Proportion of early MG-ADL responders during treatment (early responders with first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4） | The MG-ADL is a categorical scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function (total score 0 to 24). Participants with a first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4 are considered early responders. | Baseline to week 4 |
| Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L) | The EQ-5D-5L is a widely used questionnaire designed to assess health status in adults. The measure is divided into two distinct sections, the descriptive system and the EQ visual analogue scale (EQ VAS). The first section includes one item addressing each of five dimensions (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression). Participants rate each of these items from 1 of the 5 levels: no problems, slight problems, moderate problems, severe problems, or unable to/extreme. A composite health state is then defined by combining the levels for each dimension into a 5-digit number. The second section includes the EQ visual analogue scale (EQ VAS) that measures self-rated (global) health status utilizing a vertically oriented visual analogue scale where 100 represents the "best imaginable health state" and 0 represents the "worst imaginable health state." Respondents are asked to rate their current health by placing a mark along this continuum. | Baseline to Month 6 |
| Proportion of participants achieving a reduction from baseline of ≥ 3 points in MGC total score at Month 6 | The MGC is a 10-item instrument that measures the symptoms and signs of MG based on physician examination and patient history. Items relate to ptosis, double vision, eye closure, talking, chewing, swallowing, breathing, neck flexion, shoulder abduction, and hip flexion. Each item is scored on an ordinal scale with 4 possible categories and weighted. The total score ranges from 0 to 50, where higher scores indicating more severe impairments. | Baseline to Month 6 |
| Change from baseline in MG-ADL total score | The MG-ADL is a categorical scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function (total score 0 to 24). | Baseline to Month 66 |
| Proportion of participants achieving a reduction from core part in oral corticosteroids (OCS) dose till the end of extension part | Participants receiving oral corticosteroids are required to be on a stable dose for at least 4 weeks prior to baseline. The dose can be reduced or discontinued during the open label extension period at investigator discretion. Oral corticosteroids use will be recorded. | Baseline to month 66 |
| Incidence of adverse events | Incidence of adverse events including changes in clinical laboratory values, vital signs, electrocardiograms and suicidality results qualifying and reported as AEs. | Month 7 to month 66 |
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References
Clinical Trials Gov: A Study to Investigate the Efficacy, Safety and Tolerability of Remibrutinib Versus Placebo in Adult Patients With Generalized Myasthenia GravisOther trials to consider
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