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

NCT06517758 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CLNP023Q123012023-507064-39-00
• Study Type: interventional
• Target: 146
• Locations: 17 countries
• Sites: 112

Brief 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.

Conditions

Generalized Myasthenia Gravis

Keywords

Myasthenia Gravis; gMG; randomized; placebo-controlled; double-blind; phase III; AChR+; SOC treatment; iptacopan; LNP023

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Change from baseline to Month 6 in Quantitative MG (QMG) total score

  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

  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

  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

  Baseline to Month 6

• Change from baseline to Month 6 in Myasthenia Gravis Composite (MGC) total score

  Baseline to Month 6

Study Arms (2)

Iptacopan

EXPERIMENTAL

Iptacopan orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months

Drug: Iptacopan

Matching Placebo

PLACEBO COMPARATOR

Placebo orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months

Other: Matching Placebo

Interventions

Matching Placebo OTHER

Hard gelatin capsule

Matching Placebo

Iptacopan DRUG

Hard gelatin capsule

Iptacopan

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (112)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

Fullerton Neuro and Headache Ctr

Fullerton, California, 92835, United States

RECRUITING

SC3 Research Pasadena

Pasadena, California, 91105, United States

RECRUITING

California Pacific Medical Center

Sacramento, California, 94115, United States

RECRUITING

Neurology Offices Of South Florida

Boca Raton, Florida, 33428, United States

WITHDRAWN

Superior Associates in Research LLC

Hialeah, Florida, 33012, United States

WITHDRAWN

Augusta University Georgia

Augusta, Georgia, 30912, United States

RECRUITING

Hawaii Pacific Neuroscience LLC

Honolulu, Hawaii, 96817, United States

WITHDRAWN

University of Chicago Medical Centr

Chicago, Illinois, 60637, United States

RECRUITING

Prairie Heart Institute

Springfield, Illinois, 62769, United States

RECRUITING

Mid Atlantic Epilepsy and Sleep Ctr

Bethesda, Maryland, 20817-1807, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Neuroscience Research Ctr

Canton, Ohio, 44718, United States

WITHDRAWN

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

WITHDRAWN

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt University Medical CenterX

Nashville, Tennessee, 37221, United States

RECRUITING

Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

RECRUITING

Central TX Neuro Consultants P A

Round Rock, Texas, 78681, United States

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Center for Neurological Disorders G

Greenfield, Wisconsin, 53228-1321, United States

RECRUITING

Novartis Investigative Site

Buenos Aires, C1012AAR, Argentina

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Novartis Investigative Site

Córdoba, X5004AOA, Argentina

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Novartis Investigative Site

Joinville, Santa Catarina, 89202-165, Brazil

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Novartis Investigative Site

São Paulo, 04038-002, Brazil

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Novartis Investigative Site

Hefei, Anhui, 230001, China

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Novartis Investigative Site

Guangzhou, Guangdong, 510515, China

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Novartis Investigative Site

Shenzhen, Guangdong, 518053, China

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Novartis Investigative Site

Shijiazhuang, Hebei, 50030, China

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Novartis Investigative Site

Changsha, Hunan, 410008, China

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Novartis Investigative Site

Suzhou, Jiangsu, 215004, China

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Novartis Investigative Site

Nanchang, Jiangxi, 330006, China

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Novartis Investigative Site

Xi'an, Shaanxi, 710075, China

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Novartis Investigative Site

Xianyang, Shaanxi, 712000, China

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Novartis Investigative Site

Beijing, 065001, China

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Novartis Investigative Site

Beijing, 100034, China

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Novartis Investigative Site

Beijing, 100730, China

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Novartis Investigative Site

Fujian, 350001, China

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Novartis Investigative Site

Jinan, 250012, China

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Novartis Investigative Site

Copenhagen, DK-2100, Denmark

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Novartis Investigative Site

Limoges, Haute Vienne, 87000, France

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Novartis Investigative Site

Garches, 92380, France

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Novartis Investigative Site

Nice, 06000, France

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Novartis Investigative Site

Paris, 75013, France

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Novartis Investigative Site

Paris, 75940, France

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Novartis Investigative Site

Würzburg, Bavaria, 97070, Germany

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Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

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Novartis Investigative Site

Bochum, 44789, Germany

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Novartis Investigative Site

Athens, 115 28, Greece

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Novartis Investigative Site

Chaïdári, 124 62, Greece

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Novartis Investigative Site

Larissa, 411 10, Greece

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Novartis Investigative Site

Pátrai, 265 04, Greece

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Novartis Investigative Site

Thessaloniki, 54636, Greece

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Novartis Investigative Site

Haifa, 3109601, Israel

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Novartis Investigative Site

Jerusalem, 9112001, Israel

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Novartis Investigative Site

Bologna, BO, 40139, Italy

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Novartis Investigative Site

Florence, FI, 50134, Italy

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Novartis Investigative Site

Genova, GE, 16132, Italy

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Novartis Investigative Site

Milan, MI, 20133, Italy

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Novartis Investigative Site

Palermo, PA, 90127, Italy

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Novartis Investigative Site

Palermo, PA, 90146, Italy

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Novartis Investigative Site

Roma, RM, 00133, Italy

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Novartis Investigative Site

Roma, RM, 00135, Italy

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Novartis Investigative Site

Roma, RM, 00189, Italy

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Novartis Investigative Site

Orbassano, TO, 10043, Italy

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Novartis Investigative Site

Naples, 80131, Italy

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Novartis Investigative Site

Narita, Chiba, 286-8520, Japan

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Novartis Investigative Site

Sapporo, Hokkaido, 0630005, Japan

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Novartis Investigative Site

Nishinomiya, Hyōgo, 6638501, Japan

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Novartis Investigative Site

Hanamaki, Iwate, 0250082, Japan

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Novartis Investigative Site

Sendai, Miyagi, 9838520, Japan

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Novartis Investigative Site

Suita, Osaka, 565-0871, Japan

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Novartis Investigative Site

Higashi-Matsuyama, Saitama, 355-0005, Japan

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Novartis Investigative Site

Shinjuku Ku, Tokyo, 160-0023, Japan

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Novartis Investigative Site

Chiba, 2608677, Japan

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Novartis Investigative Site

Fukuoka, 8128582, Japan

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Novartis Investigative Site

Fukushima, 9601295, Japan

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Novartis Investigative Site

Hiroshima, 7348551, Japan

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Novartis Investigative Site

Lublin, Lublin Voivodeship, 20-064, Poland

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Novartis Investigative Site

Warsaw, Masovian Voivodeship, 02-676, Poland

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Novartis Investigative Site

Krakow, POL, 31-505, Poland

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Novartis Investigative Site

Katowice, Silesian Voivodeship, 40-650, Poland

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Novartis Investigative Site

Bydgoszcz, 85-065, Poland

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Novartis Investigative Site

Katowice, 40-689, Poland

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Novartis Investigative Site

Krakow, 31-870, Poland

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Novartis Investigative Site

Lublin, 20-410, Poland

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Novartis Investigative Site

Poznan, 61-731, Poland

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Novartis Investigative Site

Rzeszów, 35-055, Poland

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Novartis Investigative Site

Warsaw, 01-684, Poland

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Novartis Investigative Site

Lisbon, 1349-019, Portugal

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Novartis Investigative Site

Lisbon, 1649-035, Portugal

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Novartis Investigative Site

Porto, 4099-001, Portugal

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Novartis Investigative Site

Vila Nova de Gaia, 4434 502, Portugal

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Novartis Investigative Site

Belgrade, 11000, Serbia

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Novartis Investigative Site

Niš, 18108, Serbia

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Novartis Investigative Site

Daegu, 41404, South Korea

RECRUITING

Novartis Investigative Site

Gwangju, 61469, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 03722, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 04763, South Korea

RECRUITING

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Novartis Investigative Site

Alicante, 03010, Spain

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Novartis Investigative Site

Barcelona, 08036, Spain

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Novartis Investigative Site

Lleida, 25198, Spain

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Novartis Investigative Site

Madrid, 28006, Spain

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Novartis Investigative Site

Málaga, 29010, Spain

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Novartis Investigative Site

Valencia, 46026, Spain

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Novartis Investigative Site

Inverness, Invernesshire, IV2 3RE, United Kingdom

RECRUITING

Novartis Investigative Site

Ilford, London, IG1 4HP, United Kingdom

WITHDRAWN

Novartis Investigative Site

Swinton, Manchester, M27 8FF, United Kingdom

RECRUITING

Novartis Investigative Site

Birmingham, West Midlands, B15 2TH, United Kingdom

RECRUITING

Novartis Investigative Site

Liverpool, L9 7LT, United Kingdom

WITHDRAWN

Novartis Investigative Site

London, SW17 0QT, United Kingdom

RECRUITING

Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

iptacopan

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a participant, investigator, and sponsor-blinded study. Participants, investigator staff, persons performing the assessments and the Clinical Trial Team will remain blinded to the identity of treatment from the time of randomization until database lock after all participants have completed the double-blind treatment period. The following methods will be used to ensure that blinding is properly maintained: 1. Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone involved in the study 2. The identity of the treatment will be concealed by the use of study treatments that are all identical in packaging, labeling, schedule of administration, appearance, taste, and odor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: February 12, 2024
• First Posted: July 24, 2024
• Study Start: July 31, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): May 27, 2032
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DK (1); US (19); CN (14); PT (4); ES (8); GB (7); PL (11); GR (5); FR (5); DE (3); IL (2); AR (2); KR (4); SE (2); BR (2); JP (12); IT (11)