A Phase III Study to Investigate Efficacy, Safety and Tolerability of Iptacopan Compared With Placebo in Participants Aged 18 to 85 Years With gMG.

A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Iptacopan in Patients With Generalized Myasthenia Gravis, Followed by an Open-label Extension Phase

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.

Study Overview

• Status: Recruiting
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Drug: Iptacopan; Other: Matching Placebo

Detailed Description

The study consists of a 6-month double-blind treatment period for the primary efficacy and safety analysis followed by a maximum duration of 60 month open label extension period. A safety follow up assessment will be performed, one 7 days after the last administration of study treatment and one 30 days after the last administration of study treatment for all participants.

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • Recruiting
    • Novartis Investigative Site
  • Córdoba, Argentina, X5004CDT
    • Recruiting
    • Novartis Investigative Site
  • Córdoba, Argentina, X5004AOA
    • Recruiting
    • Novartis Investigative Site
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1428AQK
      • Recruiting
      • Novartis Investigative Site
• Australia
  • Sydney
    • Camperdown, Sydney, Australia, NSW 2050
      • Recruiting
      • Novartis Investigative Site
• Brazil
  • São Paulo, Brazil, 04038-002
    • Recruiting
    • Novartis Investigative Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90560-030
      • Recruiting
      • Novartis Investigative Site
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Recruiting
      • Novartis Investigative Site
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89202-165
      • Recruiting
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Recruiting
    • Novartis Investigative Site
  • Beijing, China, 100034
    • Recruiting
    • Novartis Investigative Site
  • Beijing, China, 065001
    • Recruiting
    • Novartis Investigative Site
  • Fujian, China, 350001
    • Recruiting
    • Novartis Investigative Site
  • Jinan, China, 250012
    • Recruiting
    • Novartis Investigative Site
  • Anhui
    • Hefei, Anhui, China, 230001
      • Recruiting
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Novartis Investigative Site
    • Shenzhen, Guangdong, China, 518053
      • Recruiting
      • Novartis Investigative Site
  • Hebei
    • Shijiazhuang, Hebei, China, 50030
      • Recruiting
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410008
      • Recruiting
      • Novartis Investigative Site
  • Jiangsu
    • Suzhou, Jiangsu, China, 215004
      • Recruiting
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • Novartis Investigative Site
  • Shaanxi
    • Xi'an, Shaanxi, China, 710075
      • Recruiting
      • Novartis Investigative Site
    • Xianyang, Shaanxi, China, 712000
      • Recruiting
      • Novartis Investigative Site
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Recruiting
    • Novartis Investigative Site
• France
  • Garches, France, 92380
    • Recruiting
    • Novartis Investigative Site
  • Nice, France, 06001
    • Recruiting
    • Novartis Investigative Site
  • Paris, France, 75013
    • Recruiting
    • Novartis Investigative Site
  • Paris, France, 75940
    • Recruiting
    • Novartis Investigative Site
  • Haute Vienne
    • Limoges, Haute Vienne, France, 87000
      • Recruiting
      • Novartis Investigative Site
• Germany
  • Bochum, Germany, 44791
    • Recruiting
    • Novartis Investigative Site
  • Bochum, Germany, 44789
    • Recruiting
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Recruiting
    • Novartis Investigative Site
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • Novartis Investigative Site
    • Regensburg, Bavaria, Germany, 93053
      • Recruiting
      • Novartis Investigative Site
    • Würzburg, Bavaria, Germany, 97070
      • Recruiting
      • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Recruiting
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 28
    • Recruiting
    • Novartis Investigative Site
  • Chaïdári, Greece, 124 62
    • Recruiting
    • Novartis Investigative Site
  • Larissa, Greece, 411 10
    • Recruiting
    • Novartis Investigative Site
  • Pátrai, Greece, 265 04
    • Withdrawn
    • Novartis Investigative Site
  • Thessaloniki, Greece, 54636
    • Recruiting
    • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Novartis Investigative Site
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Novartis Investigative Site
• Italy
  • Naples, Italy, 80131
    • Recruiting
    • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40139
      • Recruiting
      • Novartis Investigative Site
  • FI
    • Florence, FI, Italy, 50134
      • Recruiting
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Recruiting
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20133
      • Recruiting
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Recruiting
      • Novartis Investigative Site
    • Palermo, PA, Italy, 90146
      • Recruiting
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00133
      • Recruiting
      • Novartis Investigative Site
    • Roma, RM, Italy, 00189
      • Recruiting
      • Novartis Investigative Site
    • Roma, RM, Italy, 00135
      • Recruiting
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Recruiting
      • Novartis Investigative Site
• Japan
  • Chiba, Japan, 2608677
    • Recruiting
    • Novartis Investigative Site
  • Fukuoka, Japan, 8128582
    • Recruiting
    • Novartis Investigative Site
  • Fukushima, Japan, 9601295
    • Recruiting
    • Novartis Investigative Site
  • Hiroshima, Japan, 7348551
    • Recruiting
    • Novartis Investigative Site
  • Chiba
    • Narita, Chiba, Japan, 286-8520
      • Recruiting
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0630005
      • Recruiting
      • Novartis Investigative Site
  • Hyōgo
    • Nishinomiya, Hyōgo, Japan, 6638501
      • Recruiting
      • Novartis Investigative Site
  • Iwate
    • Hanamaki, Iwate, Japan, 0250082
      • Recruiting
      • Novartis Investigative Site
  • Miyagi
    • Sendai, Miyagi, Japan, 9838520
      • Recruiting
      • Novartis Investigative Site
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Recruiting
      • Novartis Investigative Site
  • Saitama
    • Higashi-Matsuyama, Saitama, Japan, 355-0005
      • Recruiting
      • Novartis Investigative Site
  • Tokyo
    • Shinjuku Ku, Tokyo, Japan, 160-0023
      • Recruiting
      • Novartis Investigative Site
• Poland
  • Bydgoszcz, Poland, 85-065
    • Recruiting
    • Novartis Investigative Site
  • Katowice, Poland, 40-689
    • Recruiting
    • Novartis Investigative Site
  • Krakow, Poland, 31-870
    • Recruiting
    • Novartis Investigative Site
  • Lublin, Poland, 20-410
    • Recruiting
    • Novartis Investigative Site
  • Poznan, Poland, 61-731
    • Recruiting
    • Novartis Investigative Site
  • Rzeszów, Poland, 35-055
    • Recruiting
    • Novartis Investigative Site
  • Warsaw, Poland, 01-684
    • Recruiting
    • Novartis Investigative Site
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-064
      • Recruiting
      • Novartis Investigative Site
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-676
      • Recruiting
      • Novartis Investigative Site
  • POL
    • Krakow, POL, Poland, 31-505
      • Recruiting
      • Novartis Investigative Site
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-650
      • Recruiting
      • Novartis Investigative Site
• Portugal
  • Lisbon, Portugal, 1649-035
    • Recruiting
    • Novartis Investigative Site
  • Lisbon, Portugal, 1349-019
    • Recruiting
    • Novartis Investigative Site
  • Porto, Portugal, 4099-001
    • Recruiting
    • Novartis Investigative Site
  • Vila Nova de Gaia, Portugal, 4434 502
    • Recruiting
    • Novartis Investigative Site
• Serbia
  • Belgrade, Serbia, 11000
    • Recruiting
    • Novartis Investigative Site
  • Niš, Serbia, 18108
    • Recruiting
    • Novartis Investigative Site
• South Korea
  • Daegu, South Korea, 41404
    • Recruiting
    • Novartis Investigative Site
  • Gwangju, South Korea, 61469
    • Recruiting
    • Novartis Investigative Site
  • Seoul, South Korea, 03722
    • Recruiting
    • Novartis Investigative Site
  • Seoul, South Korea, 04763
    • Recruiting
    • Novartis Investigative Site
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Novartis Investigative Site
  • Barcelona, Spain, 08036
    • Recruiting
    • Novartis Investigative Site
  • Lleida, Spain, 25198
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Recruiting
    • Novartis Investigative Site
  • Málaga, Spain, 29010
    • Recruiting
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Recruiting
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Recruiting
      • Novartis Investigative Site
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Novartis Investigative Site
• United Kingdom
  • Liverpool, United Kingdom, L9 7LT
    • Withdrawn
    • Novartis Investigative Site
  • London, United Kingdom, NW1 2BU
    • Recruiting
    • Novartis Investigative Site
  • London, United Kingdom, SW17 0QT
    • Recruiting
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Recruiting
    • Novartis Investigative Site
  • Invernesshire
    • Inverness, Invernesshire, United Kingdom, IV2 3RE
      • Recruiting
      • Novartis Investigative Site
  • London
    • Ilford, London, United Kingdom, IG1 4HP
      • Withdrawn
      • Novartis Investigative Site
  • Manchester
    • Swinton, Manchester, United Kingdom, M27 8FF
      • Recruiting
      • Novartis Investigative Site
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Recruiting
      • Novartis Investigative Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Honor Health Research Institute
      • Principal Investigator: Suraj Muley
      • Contact: Kristy Osgood; Email: kosgood@honorhealth.com
  • California
    • Fullerton, California, United States, 92835
      • Recruiting
      • Fullerton Neuro and Headache Ctr
      • Principal Investigator: Jack H Florin
      • Contact: Alexandra Vasquez; Phone Number: 714-738-0800; Email: avasquez@fullertonneuro.net
    • Pasadena, California, United States, 91105
      • Recruiting
      • SC3 Research Pasadena
      • Principal Investigator: M Lorraine Purino
      • Contact: Charles Krinel; Email: Charles.krinel@neurosearch-usa.com
    • Sacramento, California, United States, 94115
      • Recruiting
      • California Pacific Medical Center
      • Principal Investigator: Liberty Jenkins
      • Contact: Phone Number: 415-600-3604
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Withdrawn
      • Neurology Offices of South Florida
    • Hialeah, Florida, United States, 33012
      • Withdrawn
      • Superior Associates in Research LLC
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Augusta University Georgia
      • Principal Investigator: Benjamin Barnes
      • Contact: Christian Ryan; Phone Number: 706-721-6411; Email: chrryan@augusta.edu
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Withdrawn
      • Hawaii Pacific Neuroscience LLC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Centr
      • Principal Investigator: Kourosh Rezania
      • Contact: Deekshitha Turaka; Phone Number: 773-702-6222; Email: deekshitha.turaka@bsd.uchicago.edu
    • Springfield, Illinois, United States, 62769
      • Recruiting
      • Prairie Heart Institute
      • Principal Investigator: Raghav Govindarajan
      • Contact: Megan Kaler; Phone Number: 217-492-9100; Email: mkaler@prairieresearch.com
  • Maryland
    • Bethesda, Maryland, United States, 20817-1807
      • Recruiting
      • Mid Atlantic Epilepsy and Sleep Ctr
      • Principal Investigator: Jonathan Ross
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Amanda Guidon
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
      • Contact: Phone Number: 313-916-6781
      • Principal Investigator: Kavita Grover
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Shruti Raja
      • Contact: Kinjal Patel; Email: kinjal.patel@emory.edu
  • Ohio
    • Canton, Ohio, United States, 44718
      • Withdrawn
      • Neuroscience Research Ctr
    • Columbus, Ohio, United States, 43210
      • Withdrawn
      • Ohio State University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Penn Presbyterian Medical Center
      • Principal Investigator: Sami Khella
      • Contact: Thomas Keenan; Phone Number: 215-662-8570; Email: thomas.keenan@pennmedicine.upenn.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37221
      • Recruiting
      • Vanderbilt University Medical CenterX
      • Principal Investigator: Amanda Peltier
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Nerve And Muscle Center Of Texas
      • Contact: Amy Megerle; Email: houneuamy@msn.com
      • Principal Investigator: Aziz Shaibani.
    • Round Rock, Texas, United States, 78681
      • Withdrawn
      • Central TX Neuro Consultants P A
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228-1321
      • Recruiting
      • Center for Neurological Disorders G
      • Principal Investigator: Bhupendra Khatri
      • Contact: Emily Barraza; Phone Number: 414-214-7275; Email: Emily.barraza@cndmilwaukee.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients with generalized Myasthenia Gravis (age 18-85 years) at screening
• Positive serology testing for AChR+ antibody at screening
• 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.
• The confirmation of the diagnosis of gMG should be documented and supported by ≥1 of the following 3 tests:
• History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation.
• History of positive test with short-acting acetylcholinesterase inhibitors (e.g. neostigmine or edrophonium chloride)
• Patient has demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician.
• Baseline MG-ADL score ≥6, with ≥50% of the total score due to non-ocular symptoms
• Participants receiving at least one of the following treatments for gMG for ≥ 6 months prior to baseline;
• One or more NSISTs or
• plasmapheresis, plasma exchange, or intravenous immunoglobulin (at least quarterly) to control symptoms despite treatment with steroids and NSISTs; or
• an approved FcRN antagonist approved for gMG; or
• rituximab or
• other approved gMG disease modifying therapies excluding complement inhibitors.
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster was required, the vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated at the start of study treatment and continued until at least 2 weeks after vaccination or booster was completed.

Note: For US sites participating in Study CLNP023Q12301, the completion of the meningococcal vaccination or booster is required for patients with gMG prior to initiating study treatment, irrespective of prophylactic antibiotic use.

Exclusion Criteria:

• Have been treated with intravenous immunoglobulin (IVIG)/plasma exchange (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.

• Participants with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including patients who test positive for an active viral infection at screening with: Active Hepatitis B Virus (HBV); Active Hepatitis C Virus (HCV);

  • Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with a cluster of differentiation 4 (CD4) count

    • 200 cells/mm3
• Female participants who are pregnant or lactating, or are intending to become pregnant.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using effective methods of contraception during dosing of study treatment and an additional one week following cessation of study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms).
• Active systemic bacterial, viral (including COVID-19) or fungal infection or any major episode of infection that required hospitalization or injectable antimicrobial therapy within 14 days prior to study drug administration.
• History of recurrent invasive infections caused by encapsulated organisms, e.g., N. meningitidis and S. pneumoniae.
• Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iptacopan; Iptacopan orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months	Drug: Iptacopan; Hard gelatin capsule
Placebo Comparator: Matching Placebo; Placebo orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months	Other: Matching Placebo; Hard gelatin capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 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

Outcome Measure	Measure Description	Time Frame
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
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 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
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)
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.	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/or 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
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	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
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 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 participants with a reduction of ≥ 3 points from baseline to Month 6 in 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 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 66 (end of extension phase)
Proportion of participants achieving a reduction in oral corticosteroids (OCS) dose compared to Core Part that was maintained up to 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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): May 27, 2032

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Myasthenia Gravis; phase III; randomized; placebo-controlled; double-blind; gMG; LNP023; iptacopan; AChR+; SOC treatment
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis; iptacopan
• Other Study ID Numbers: CLNP023Q12301; 2023-507064-39-00 (Other Identifier: EUCTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No