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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
85 Years
Healthy volunteers
No
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
Primary outcome measure(s)
Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score — Baseline to Month 6 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.
Trial sites (116)
Facility
City
Region
Status
Honor Health Research Institute
Scottsdale
Arizona
Fullerton Neuro and Headache Ctr
Fullerton
California
California Pacific Medical Center
Sacramento
California
Augusta University Georgia
Augusta
Georgia
University of Chicago Medical Centr
Chicago
Illinois
Prairie Heart Institute
Springfield
Illinois
Mid Atlantic Epilepsy and Sleep Ctr
Bethesda
Maryland
Massachusetts General Hospital
Boston
Massachusetts
Henry Ford Health System
Detroit
Michigan
Duke University Medical Center
Durham
North Carolina
Penn Presbyterian Medical Center
Philadelphia
Pennsylvania
Vanderbilt University Medical CenterX
Nashville
Tennessee
Nerve and Muscle Center of Texas
Houston
Texas
Novartis Investigative Site
CABA
Buenos Aires
Novartis Investigative Site
Córdoba
Córdoba Province
Novartis Investigative Site
Rosario
Santa Fe Province
Novartis Investigative Site
Buenos Aires
Argentina
Novartis Investigative Site
Caba
Argentina
Novartis Investigative Site
Caba
Argentina
Novartis Investigative Site
Capital Federal
Argentina
Novartis Investigative Site
Córdoba
Argentina
Novartis Investigative Site
Camperdown
Sydney
Novartis Investigative Site
Porto Alegre
Rio Grande do Sul
Novartis Investigative Site
Porto Alegre
Rio Grande do Sul
Novartis Investigative Site
Joinville
Santa Catarina
Novartis Investigative Site
Bahia
Brazil
Novartis Investigative Site
São Paulo
Brazil
Novartis Investigative Site
Hefei
Anhui
Novartis Investigative Site
Guangzhou
Guangdong
Novartis Investigative Site
Shenzhen
Guangdong
Novartis Investigative Site
Shijiazhuang
Hebei
Novartis Investigative Site
Changsha
Hunan
Novartis Investigative Site
Suzhou
Jiangsu
Novartis Investigative Site
Xi'an
Shaanxi
Novartis Investigative Site
Xianyang
Shaanxi
Novartis Investigative Site
Beijing
China
Novartis Investigative Site
Beijing
China
Novartis Investigative Site
Beijing
China
Novartis Investigative Site
Fujian
China
Novartis Investigative Site
Jinan
China
+ 76 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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