Clinical trial NCT06517758: A Phase III Study to Investigate Efficacy, Safety and Tolerability of Iptacopan Compared With Placebo in Participants Aged 18 to 75 Years With gMG.
Official 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 (gMG), Followed by an Open Label Extension Phase
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Generalized Myasthenia Gravis
Keywords: Myasthenia Gravis
gMG
randomized
placebo-controlled
double-blind
phase III
AChR+
SOC treatment
iptacopan
LNP023
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-07-24
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

Detailed description: The study consists of a 6-month double-blind treatment period for the primary efficacy and safety analysis followed by a 24 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.

Eligibility criteria: Inclusion Criteria:

* Adult patients with generalized Myasthenia Gravis (age 18-75 years)
* Positive serology testing for AChR+ antibody at screening
* Myasthenia Gravis Foundation of America (MGFA) Class II-IV gMG and likely not in need v 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 edrophonium chloride test
* 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 not optimally controlled for ≥ 6 months on
* just one NSIST; or
* two or more NSISTs; or
* on frequent (at least quarterly) plasmapheresis, plasma exchange, or intravenous immunoglobulin to control symptoms despite treatment with steroids and NSISTs; or
* one of the following gMG treatments:
* a FcRN antagonist approved for gMG
* rituximab
* other approved gMG therapies excluding complement inhibitors.
* Consistent with all other iptacopan trials, participants will have to be vaccinated against Neisseria meningitidis and Streptococcus pneumoniae. In addition, participants will be vaccinated against Haemophilus influenzae, depending on the local regulations and on the availability of this vaccine in the countries of study conduct. The vaccination will be performed at least 2 weeks prior to first dosing with iptacopan, covering as many serotypes as possible. If iptacopan treatment will start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment must be initiated and administered until 2 weeks post vaccination.

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): serologic panel test results indicative of an active (acute or chronic) infection; Active Hepatitis C Virus (HCV): serology positive for HCV-Ab; 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, unless they are using effective methods of contraception during dosing of study treatment.
* 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 outcomes:
measure: Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: Change from baseline to Month 6 in Quantitative MG (QMG) total score
timeFrame: Baseline to Month 6
measure: Proportion of participants with ≥ 5 points reduction from baseline to Month 6 of QMG total score without rescue medication and strongly confounding prohibited medication
timeFrame: Baseline to Month 6
measure: 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
timeFrame: Baseline to Month 6
measure: Change from baseline to Month 6 in Myasthenia Gravis Composite (MGC) total score
timeFrame: Baseline to Month 6
measure: Change from baseline to Month 6 in revised MG Quality of Life Questionnaire (MG-QOL15r) survey score
timeFrame: Baseline to Month 6
measure: Incidence of adverse events
timeFrame: Baseline to Month 6
measure: Proportion of time patients showed a reduction from baseline of ≥ 2 points in MG-ADL score, up to the end of the study
timeFrame: Baseline to Month 6
measure: Proportion of early MG-ADL responders during treatment (early responders with first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4）
timeFrame: Baseline to Month 6
measure: Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L)
timeFrame: Baseline to Month 6
measure: Change from baseline in MG-ADL total score
timeFrame: Baseline to Month 30 (end of extension phase)
measure: Proportion of participants achieving a reduction from core part in oral corticosteroids (OCS) dose till the end of extension part
timeFrame: Month 6 (end of core phase) to Month 30 (end of extension phase)
measure: Incidence of adverse events
timeFrame: Baseline to Month 30 (end of extension phase)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Fullerton
country: United States
facility: Fullerton Neuro and Headache Ctr
state: California
city: Pasadena
country: United States
facility: SC3 Research Pasadena
state: California
city: Boca Raton
country: United States
facility: Neurology Offices Of South Florida
state: Florida
city: Hialeah
country: United States
facility: Superior Associates in Research LLC
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience LLC
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago Medical Centr
state: Illinois
city: Springfield
country: United States
facility: Prairie Heart Institute
state: Illinois
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Canton
country: United States
facility: Neuroscience Research Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical CenterX
state: Tennessee
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: Round Rock
country: United States
facility: Central TX Neuro Consultants P A
state: Texas
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shenzhen
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shijiazhuang
country: China
facility: Novartis Investigative Site
state: Hebei
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Xianyang
country: China
facility: Novartis Investigative Site
state: Shaanxi
city: Xian
country: China
facility: Novartis Investigative Site
state: Shaanxi
city: Beijing
country: China
facility: Novartis Investigative Site
city: Fujian
country: China
facility: Novartis Investigative Site
city: Jinan
country: China
facility: Novartis Investigative Site
city: Chaidari
country: Greece
facility: Novartis Investigative Site
state: Attiki
city: Larissa
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Narita
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukushima city
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Nishinomiya
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Hanamaki
country: Japan
facility: Novartis Investigative Site
state: Iwate
city: Sendai-shi
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Higashimatsuyama
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Shinjuku Ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
state: Lubelskie
city: Katowice
country: Poland
facility: Novartis Investigative Site
state: Slaskie
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Vila Nova De Gaia
country: Portugal
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Pozuelo de Alarcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Inverness
country: United Kingdom
facility: Novartis Investigative Site
state: Invernesshire
city: Ilford
country: United Kingdom
facility: Novartis Investigative Site
state: London
city: Swinton
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: