Clinical trial NCT04115293: Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis
Official title: A Phase 3, Multicenter, Randomized, Double Blind, Placebo-Controlled Study to Confirm the Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myasthenia Gravis, Generalized
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2019-10-04
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The RAISE study is a multicenter, randomized, double-blind, placebo controlled study to confirm the efficacy, safety, and tolerability of zilucoplan in subjects with generalized Myasthenia Gravis. Subjects will be randomized in a 1:1 ratio to receive daily SC doses of 0.3 mg/kg zilucoplan or placebo for 12 weeks.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of gMG \[Myasthenia Gravis Foundation of America (MGFA) Class II-IV\] at Screening
* Positive serology for acetylcholine receptor (AChR) autoantibodies
* MG-ADL Score of ≥ 6 at Screening and Baseline
* QMG score ≥ 12 at Screening and Baseline
* No change in corticosteroid dose for at least 30 days prior to Baseline or anticipated to occur during the 12-week Treatment Period
* No change in immunosuppressive therapy, including dose, for at least 30 days prior to Baseline or anticipated to occur during the 12-week Treatment Period

Exclusion Criteria:

* Thymectomy within 12 months prior to Baseline or scheduled to occur during the 12 week Treatment Period
* History of meningococcal disease
* Current or recent systemic infection within 2 weeks prior to Baseline or injection requiring intravenous (IV) antibiotics within 4 weeks prior to Baseline

Primary outcomes:
measure: Change From Baseline (CFB) to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Total Score
timeFrame: From Baseline to End of Treatment (Week 12)
Secondary outcomes:
measure: Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Total Score
timeFrame: From Baseline to End of Treatment (Week 12)
measure: Change From Baseline to Week 12 in the Myasthenia Gravis Composite (MGC) Scale Total Score
timeFrame: From Baseline to End of Treatment (Week 12)
measure: Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life Revised (MG-QoL15r) Scale Total Score
timeFrame: From Baseline to End of Treatment (Week 12)
measure: Time to First Receipt of Rescue Therapy Over the 12-week Treatment Period
timeFrame: From Baseline to End of Treatment (Week 12)
measure: Percentage of Participants Achieving Minimal Symptom Expression (MSE) at Week 12 Without Rescue Therapy
timeFrame: End of Treatment (Week 12)
measure: Percentage of Participants Achieving a ≥ 3-point Reduction in MG-ADL Score at Week 12 Without Rescue Therapy
timeFrame: End of Treatment (Week 12)
measure: Percentage of Participants Achieving a ≥5-point Reduction in QMG Score Without Rescue Therapy at Week 12
timeFrame: End of Treatment (Week 12)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Baseline (Day 1) to Safety Follow-up visit (19 Weeks [12 weeks Treatment Period plus up to 7 weeks Follow-up])
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Site 41: Diagnostic and Medical Clinic
state: Alabama
city: Phoenix
country: United States
facility: Site 116: Neuromuscular Clinic and Research Center
state: Arizona
city: Los Angeles
country: United States
facility: Site 4: University of Southern California
state: California
city: Orange
country: United States
facility: Site 31: University of California Irvine
state: California
city: Pasadena
country: United States
facility: Site 220: Investigator Site
state: California
city: San Francisco
country: United States
facility: Site 160: Forbes Norris MDA/ALS Research and Treatment Center
state: California
city: New Haven
country: United States
facility: Site 24: Yale University
state: Connecticut
city: Washington
country: United States
facility: Site 27: George Washington University
state: District of Columbia
city: Miami
country: United States
facility: Site 182: Gelasio Baras Neurology
state: Florida
city: Tampa
country: United States
facility: Site 25: University of South Florida
state: Florida
city: Augusta
country: United States
facility: Site 135: Augusta University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Site 176: Hawaii Pacific Neuroscience
state: Hawaii
city: Glenview
country: United States
facility: Site 188: North Shore Medical Group - Glenview
state: Illinois
city: Indianapolis
country: United States
facility: Site 156: Indiana University Health Neuroscience Center
state: Indiana
city: Kansas City
country: United States
facility: Site 32: Kansas University Medical Center Research Institute
state: Kansas
city: Foxboro
country: United States
facility: Site 221: Neurology Center of New England
state: Massachusetts
city: Detroit
country: United States
facility: Site 33: Detroit medical Center - University Health Center
state: Michigan
city: East Lansing
country: United States
facility: Site 49: Michigan State University
state: Michigan
city: Minneapolis
country: United States
facility: Site 127: University of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: Site 134: Neurology and Sleep Disorders Clinic
state: Missouri
city: Las Vegas
country: United States
facility: Site 117: Las Vegas Clinic
state: Nevada
city: Great Neck
country: United States
facility: Site 123: Northwell Health Neuroscience Institute
state: New York
city: New York
country: United States
facility: Site 23: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Site 47: Mount Sinai Hospital
state: New York
city: Chapel Hill
country: United States
facility: Site 22: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Site 15: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Site 122: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Site 38: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Site 40: Allegheny Neurological Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Site 128: Medical University of South Carolina
state: South Carolina
city: Cordova
country: United States
facility: Site 185: Neurology Clinic Cordova
state: Tennessee
city: Austin
country: United States
facility: Site 131: Austin Neuromuscular Center
state: Texas
city: Dallas
country: United States
facility: Site 19: University of Texas Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: Site 39: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: Site 164: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Site 154: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Site 45: Center for Neurological Disorders
state: Wisconsin
city: London
country: Canada
facility: Site 44: London Health Sciences Centre University Hospital
state: Ontario
city: Montréal
country: Canada
facility: Site 11: Montreal Neurological Institute and Hospital (McGill University)
state: Quebec
city: Angers Cedex 9
country: France
facility: Site 191: Centre Hosptitalier Universitaire d'Angers
city: Lille
country: France
facility: Site 204: Centre Hospitalier Régional Universitaire de Lille
city: Nice
country: France
facility: Site 118: Hôpital Pasteur
city: Paris
country: France
facility: Site 105: Pitié-Salpêtrière University Hospital
city: Strasbourg
country: France
facility: Site 137: Les Hôpitaux Universitaires de Strasbourg
city: Göttingen
country: Germany
facility: Site 150: Universitätsmedizin Göttingen
city: Tübingen
country: Germany
facility: Site 129: Universitätsklinikum Tübingen
city: Milan
country: Italy
facility: Site 126: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Roma
country: Italy
facility: Site 132: Università Cattolica del Sacro Cuore - Campus di Milano
city: Narita
country: Japan
facility: Site 169: International University of Health and Welfare Narita Hospital
state: Chiba
city: Chiba
country: Japan
facility: Site 151: Chiba University Hospital
city: Iwata
country: Japan
facility: Site 136: General Hanamaki Hospital
city: Kita-gun
country: Japan
facility: Site 179: Kagawa University Hospital - Collagen disease/Rheumatic int
city: Nagasaki
country: Japan
facility: Site 146: Nagasaki University Hospital
city: Sapporo
country: Japan
facility: Site 152: Hokkaido Medical Center
city: Sendai
country: Japan
facility: Site 144: Sendai Medical Center
city: Tokyo
country: Japan
facility: Site 153: Toho University Ohashi Medical Center
city: Tokyo
country: Japan
facility: Site 163: Tokyo Medical University Hospital
city: Tokyo
country: Japan
facility: Site 141: Keio University Hospital
city: Tokyo
country: Japan
facility: Site 165: Osaka University Hospital
city: Bergen
country: Norway
facility: Site 140: Haukeland University Hospital / Health Bergen
city: Oslo
country: Norway
facility: Site 143: Oslo Universitetssykehus
city: Lublin
country: Poland
facility: Site 205: Prywatny Gabinet Lekarski Urszula Chyrchel-Paszkiewicz
state: Lubelskie
city: Nowa Sól
country: Poland
facility: Site 194: Twoja Przychodnia - Centrum Medyczne Nowa Sól
state: Lubuskie
city: Łódź
country: Poland
facility: Site 214: AmiCare Centrum Medyczne
state: Lódzkie
city: Kraków
country: Poland
facility: Site 192: Krakowski Szpital Specjalistyczny im. Jana Pawła II
state: Malopolskie
city: Warszawa
country: Poland
facility: Site 201: Centrum Medyczne Pratia - Warszawa
state: Mazowieckie
city: Katowice
country: Poland
facility: Site 195: Wielospecjalistyczna Poradnia Lekarska Synapsis
state: Slaskie
city: Katowice
country: Poland
facility: Site 213: Niepubliczny Zakład Opieki Zdrowotnej NOVO-MED
state: Slaskie
city: Poznań
country: Poland
facility: Site 209: Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD
state: Wielkopolskie
city: Kraków
country: Poland
facility: Site 193: Krakowska Akademia Neurologii - Centrum Neurologii Kliniczne
city: Kraków
country: Poland
facility: Site 211: Specjalistyczne Gabinety Sp. z o.o.
city: Lublin
country: Poland
facility: Site 210: Clinhouse Centrum Medyczne
city: Barcelona
country: Spain
facility: Site 133: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Site 168: Hospital de la Santa Creu i Sant Pau
city: Bilbao
country: Spain
facility: Site 138: Hospital Universitario de Basurto
city: Oxford
country: United Kingdom
facility: Site 119: Oxford University Hospitals NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Site 130: Royal Hallamshire Hospital
Study officials:
affiliation: 0018445992273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: Howard JF Jr, Bresch S, Genge A, Hewamadduma C, Hinton J, Hussain Y, Juntas-Morales R, Kaminski HJ, Maniaol A, Mantegazza R, Masuda M, Sivakumar K, Smilowski M, Utsugisawa K, Vu T, Weiss MD, Zajda M, Boroojerdi B, Brock M, de la Borderie G, Duda PW, Lowcock R, Vanderkelen M, Leite MI; RAISE Study Team. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023 May;22(5):395-406. doi: 10.1016/S1474-4422(23)00080-7.
citation: Weiss MD, Freimer M, Leite MI, Maniaol A, Utsugisawa K, Bloemers J, Boroojerdi B, Howard E, Savic N, Howard JF Jr. Improvement of fatigue in generalised myasthenia gravis with zilucoplan. J Neurol. 2024 May;271(5):2758-2767. doi: 10.1007/s00415-024-12209-3. Epub 2024 Feb 24.
citation: de la Borderie G, Chimits D, Boroojerdi B, Brock M, Duda PW, Grimson F, Mahoney P, Strimenopoulou F, Cutter G, Aban I, Brauner S, Petersson M, Howard JF Jr, Bennett N. Maintenance of zilucoplan efficacy in patients with generalised myasthenia gravis up to 24 weeks: a model-informed analysis. Ther Adv Neurol Disord. 2024 Sep 21;17:17562864241279125. doi: 10.1177/17562864241279125. eCollection 2024.