A Phase III Study to Investigate Efficacy, Safety and Tolerability of Iptacopan Compared With Placebo in Participants Aged 18 to 75 Years With gMG.
NCT Number: NCT06517758
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Generalized Myasthenia Gravis
Interventions: DRUG: Iptacopan|OTHER: Matching Placebo
Sponsor: Novartis Pharmaceuticals
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 146
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-31
Completion Date: 2029-01-12
Locations: Fullerton Neuro and Headache Ctr ., Fullerton, California, 92835, United States|Neurology Offices Of South Florida, Boca Raton, Florida, 33482, United States|Central TX Neuro Consultants P A, Round Rock, Texas, 78681, United States|Novartis Investigative Site, Larissa, GR, 411 10, Greece|Novartis Investigative Site, Patras, 265 00, Greece|Novartis Investigative Site, Lisboa, 1349-019, Portugal|Novartis Investigative Site, Lisboa, 1649 035, Portugal|Novartis Investigative Site, Barcelona, Catalunya, 08036, Spain|Novartis Investigative Site, Alicante, Comunidad Valenciana, 03010, Spain|Novartis Investigative Site, Pozuelo de Alarcon, Madrid, 28223, Spain

Summary:
The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in patients with AChR+ gMG who are on stable SOC treatment. Participants who meet the eligibility criteria will be randomized in a ratio of 1:1, to receive either iptacopan or matching placebo, for 6 months (180 days) while continuing on a stable SOC treatment. The randomization will be stratified based on region.

Primary Outcome Measures: Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score, The MG-ADL is an 8 item interviewer led patient reporting 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. The scores ranges from 0 to 24, with a higher score indicating more disability., Baseline to Month 6
Secondary Outcome Measures: Change from baseline to Month 6 in Quantitative MG (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., Baseline to Month 6|Proportion of participants with ≥ 5 points reduction from baseline to Month 6 of QMG total score without rescue medication and 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., Baseline to Month 6|Proportion of participants with ≥ 3 points reduction from baseline to Month 6 of MG-ADL total score without rescue medication and strongly confounding prohibited medication, The MG-ADL is an 8 item patient reporting 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. The scores ranges from 0 to 24, with a higher score indicating more disability., Baseline to Month 6|Change from baseline to Month 6 in Myasthenia Gravis Composite (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 indicate more severe impairments., Baseline to Month 6|Change from baseline to Month 6 in revised MG 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, Any significant and notable changes in clinical laboratory values, vital signs, electrocardiograms and Columbia Suicidal Severity Rating Scale., Baseline to Month 6|Proportion of time patients showed a reduction from baseline of ≥ 2 points in MG-ADL score, up to the end of the study, The MG-ADL is an 8 item patient reporting 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. The scores ranges from 0 to 24, with a higher score indicating more disability., 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 an 8 item patient reporting 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. The scores ranges from 0 to 24, with a higher score indicating more disability., Baseline to Month 6|Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L), This 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 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|Change from baseline in MG-ADL total score, The MG-ADL is an 8 item patient reporting 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. The scores ranges from 0 to 24, with a higher score indicating more disability., Baseline to Month 30 (end of extension phase)|Proportion of participants achieving a reduction from core part in oral corticosteroids (OCS) dose till the end of extension part, Long-term effect of iptacopan in patients with gMG will be assessed by the proportion of patients that had a reduction in dose or discontinuation of oral corticosteroids, higher proportion would indicate greater long-term effect., Month 6 (end of core phase) to Month 30 (end of extension phase)|Incidence of adverse events, Any significant and notable changes in clinical laboratory values, vital signs, electrocardiograms and Columbia Suicidal Severity Rating Scale., Baseline to Month 30 (end of extension phase)