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NCT Number: NCT06517758

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

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.

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Key information

Conditions

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

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, CABA, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Iptacopan

Drug

Hard gelatin capsule

Matching Placebo

Other

Hard gelatin capsule

Primary outcomes

  1. Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score

    Time frame: 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.

Secondary outcomes

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

    Time frame: Baseline to Month 6

    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.

  2. 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

    Time frame: Baseline to Month 6

    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.

  3. 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

    Time frame: Baseline 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.

  4. 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

    Time frame: 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.

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

    Time frame: Baseline to 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 indicate more severe impairments.

  6. Change from baseline to Month 6 in revised MG Quality of Life Questionnaire (MG-QOL15r) survey score

    Time frame: Baseline to Month 6

    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.

  7. Incidence of adverse events

    Time frame: Baseline to Month 6

    Any significant and notable changes in clinical laboratory values, vital signs, electrocardiograms and Columbia Suicidal Severity Rating Scale.

  8. Proportion of time during which participants showed a reduction of ≥ 2 points in MG-ADL total score that was maintained up to Month 6

    Time frame: Baseline 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.

  9. Proportion of early MG-ADL responders during treatment (early responders with first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4）

    Time frame: Baseline 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.

  10. Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L)

    Time frame: Baseline to Month 6

    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.

  11. Proportion of participants with a reduction of ≥ 3 points from baseline to Month 6 in MGC total score

    Time frame: Baseline to 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 indicate more severe impairments.

  12. Change from baseline in MG-ADL total score

    Time frame: Baseline to Month 66 (end of extension phase)

    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.

  13. Proportion of participants achieving a reduction in oral corticosteroids (OCS) dose compared to Core Part that was maintained up to end of Extension Part

    Time frame: Month 6 (end of core phase) to Month 30 (end of extension phase)

    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.

  14. Incidence of adverse events

    Time frame: Baseline to Month 30 (end of extension phase)

    Any significant and notable changes in clinical laboratory values, vital signs, electrocardiograms and Columbia Suicidal Severity Rating Scale.

Study contacts

Contact information is provided by the study sponsor or research team.

Novartis Pharmaceuticals

CONTACT

[email protected]

1-888-669-6682

Novartis Pharmaceuticals

CONTACT

+41613241111

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2027
Study completion
2032
First posted
Jul 24, 2024
Registry last updated
Jun 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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