Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis
- Conditions
- Myasthenia Gravis, Generalized
- Interventions
- Drug: Placebo
- Registration Number
- NCT04115293
- Lead Sponsor
- Ra Pharmaceuticals, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 174
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.3 mg/kg zilucoplan (RA101495) zilucoplan (RA101495) - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Change From Baseline (CFB) to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Total Score From Baseline to End of Treatment (Week 12) The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and their effects on daily activities. Each item in the scale scored 0 to 3 (0=None, 3=severe disease) point scale. The total score was the sum of all individual item scores and ranged from 0 to 24. Higher scores indicated more severe disability due to MG. A decrease from Baseline score indicated improvement.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Total Score From Baseline to End of Treatment (Week 12) The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consisted of 13 items. Each item in the scale scored on a 0 to 3-point scale, ranging from 0 (no weakness) to 3 (severe weakness), summing up to the overall score range from 0 to 39. Higher scores indicated more severe impairment. A decrease from Baseline score indicated improvement.
Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life Revised (MG-QoL15r) Scale Total Score From Baseline to End of Treatment (Week 12) The MG-QoL15r is a 15-item patient-reported outcome measure designed to assess quality of life in patients with MG. Each item in the scale scored on a 0 to 2-point scale (0=Not much at all, 1=Somewhat, 2=Very much). The total score was the sum of the 15 individual item scores, ranging from 0 to 30. Higher scores indicated more severe impact of the disease on aspects of the patient's life. A decrease from Baseline score indicated improvement.
Time to First Receipt of Rescue Therapy Over the 12-week Treatment Period From Baseline to End of Treatment (Week 12) Time to first receipt of rescue therapy over the 12-week treatment period (in days) was defined as the date of first rescue therapy use minus date of first Investigational Medicinal Product (IMP) + 1.
Change From Baseline to Week 12 in the Myasthenia Gravis Composite (MGC) Scale Total Score From Baseline to End of Treatment (Week 12) The total MGC score was sum of responses to 10 individual items : 1. Ptosis upward gaze (0 to 3), 2. Double vision on lateral gaze, left or right (0, to 4), 3. Eye closure (0 to 2), 4. Talking (0 to 6), 5. Chewing (0 to 6), 6. Swallowing \[0 to 6\], 7. Breathing (0 to 9), 8. Neck flexion or extension (0 to 4), 9. Shoulder abduction (0 to 5), 10. Hip flexion (0 to 5). The higher score for each item indicated severity. The total score ranged 0 to 50 with higher score indicative of severe disease activity). A decrease from Baseline score showed improvement.
Percentage of Participants Achieving Minimal Symptom Expression (MSE) at Week 12 Without Rescue Therapy End of Treatment (Week 12) Percentage of Participants achieving MSE was defined as achieving a MG-ADL value of a 0 (No MG symptoms) or 1 (Mild MG symptoms) at Week 12 and not having taken rescue therapy. Any participant with an event of death, myasthenic crisis or rescue therapy was considered as non-responders. Any other missing data was imputed using the missing at Random (MAR) assumption.
Percentage of Participants Achieving a ≥ 3-point Reduction in MG-ADL Score at Week 12 Without Rescue Therapy End of Treatment (Week 12) Percentage of participants achieving a ≥ 3-point reduction in MG-ADL Score at Week 12 without rescue therapy were reported. The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and their effects on daily activities. Each item in the scale scored on a 0 to 3 (0=None, 3=severe disease) point scale. The total score was the sum of all individual item scores and ranged from 0 to 24. Higher scores indicated more severe disability due to MG. Any participant with an event of death, myasthenic crisis or rescue therapy was considered as non-responders. Any other missing data was imputed using the MAR assumption.
Percentage of Participants Achieving a ≥5-point Reduction in QMG Score Without Rescue Therapy at Week 12 End of Treatment (Week 12) Percentage of participants achieving a ≥5-point reduction in QMG Score without rescue therapy at Week 12 were reported. The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consisted of 13 items. Each item in the scale scored on a 0 to 3-point scale, ranging from 0 (no weakness) to 3 (severe weakness), summing up to the overall score range from 0 to 39. Higher scores indicated more severe impairment. Any participant with an event of death, myasthenic crisis or rescue therapy was considered as non-responders. Any other missing data was imputed using the MAR assumption.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline (Day 1) to Safety Follow-up visit (19 Weeks [12 weeks Treatment Period plus up to 7 weeks Follow-up]) A TEAE is defined as an AE starting on or after the time of first administration of IMP and up to and including 40 days after the final dose (or last contact depending on which occurs first). Adverse events starting before the date of the first administration of IMP were not considered TEAEs.
Trial Locations
- Locations (77)
Site 4: University of Southern California
🇺🇸Los Angeles, California, United States
Site 188: North Shore Medical Group - Glenview
🇺🇸Glenview, Illinois, United States
Site 123: Northwell Health Neuroscience Institute
🇺🇸Great Neck, New York, United States
Site 40: Allegheny Neurological Associates
🇺🇸Pittsburgh, Pennsylvania, United States
Site 19: University of Texas Southwestern
🇺🇸Dallas, Texas, United States
Site 154: University of Washington
🇺🇸Seattle, Washington, United States
Site 156: Indiana University Health Neuroscience Center
🇺🇸Indianapolis, Indiana, United States
Site 32: Kansas University Medical Center Research Institute
🇺🇸Kansas City, Kansas, United States
Site 160: Forbes Norris MDA/ALS Research and Treatment Center
🇺🇸San Francisco, California, United States
Site 116: Neuromuscular Clinic and Research Center
🇺🇸Phoenix, Arizona, United States
Site 119: Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom
Site 130: Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Site 182: Gelasio Baras Neurology
🇺🇸Miami, Florida, United States
Site 220: Investigator Site
🇺🇸Pasadena, California, United States
Site 221: Neurology Center of New England
🇺🇸Foxboro, Massachusetts, United States
Site 39: University of Utah
🇺🇸Salt Lake City, Utah, United States
Site 49: Michigan State University
🇺🇸East Lansing, Michigan, United States
Site 38: Ohio State University
🇺🇸Columbus, Ohio, United States
Site 127: University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Site 23: Hospital for Special Surgery
🇺🇸New York, New York, United States
Site 122: Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Site 15: Duke University
🇺🇸Durham, North Carolina, United States
Site 137: Les Hôpitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France
Site 191: Centre Hosptitalier Universitaire d'Angers
🇫🇷Angers Cedex 9, France
Site 118: Hôpital Pasteur
🇫🇷Nice, France
Site 164: University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Site 204: Centre Hospitalier Régional Universitaire de Lille
🇫🇷Lille, France
Site 126: Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milan, Italy
Site 132: Università Cattolica del Sacro Cuore - Campus di Milano
🇮🇹Roma, Italy
Site 211: Specjalistyczne Gabinety Sp. z o.o.
🇵🇱Kraków, Poland
Site 205: Prywatny Gabinet Lekarski Urszula Chyrchel-Paszkiewicz
🇵🇱Lublin, Lubelskie, Poland
Site 44: London Health Sciences Centre University Hospital
🇨🇦London, Ontario, Canada
Site 45: Center for Neurological Disorders
🇺🇸Milwaukee, Wisconsin, United States
Site 25: University of South Florida
🇺🇸Tampa, Florida, United States
Site 135: Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Site 41: Diagnostic and Medical Clinic
🇺🇸Mobile, Alabama, United States
Site 31: University of California Irvine
🇺🇸Orange, California, United States
Site 33: Detroit medical Center - University Health Center
🇺🇸Detroit, Michigan, United States
Site 134: Neurology and Sleep Disorders Clinic
🇺🇸Columbia, Missouri, United States
Site 47: Mount Sinai Hospital
🇺🇸New York, New York, United States
Site 169: International University of Health and Welfare Narita Hospital
🇯🇵Narita, Chiba, Japan
Site 105: Pitié-Salpêtrière University Hospital
🇫🇷Paris, France
Site 150: Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Site 129: Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Site 151: Chiba University Hospital
🇯🇵Chiba, Japan
Site 153: Toho University Ohashi Medical Center
🇯🇵Tokyo, Japan
Site 165: Osaka University Hospital
🇯🇵Tokyo, Japan
Site 133: Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Site 138: Hospital Universitario de Basurto
🇪🇸Bilbao, Spain
Site 168: Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Site 195: Wielospecjalistyczna Poradnia Lekarska Synapsis
🇵🇱Katowice, Slaskie, Poland
Site 210: Clinhouse Centrum Medyczne
🇵🇱Lublin, Poland
Site 140: Haukeland University Hospital / Health Bergen
🇳🇴Bergen, Norway
Site 193: Krakowska Akademia Neurologii - Centrum Neurologii Kliniczne
🇵🇱Kraków, Poland
Site 163: Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Site 152: Hokkaido Medical Center
🇯🇵Sapporo, Japan
Site 143: Oslo Universitetssykehus
🇳🇴Oslo, Norway
Site 213: Niepubliczny Zakład Opieki Zdrowotnej NOVO-MED
🇵🇱Katowice, Slaskie, Poland
Site 209: Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD
🇵🇱Poznań, Wielkopolskie, Poland
Site 117: Las Vegas Clinic
🇺🇸Las Vegas, Nevada, United States
Site 185: Neurology Clinic Cordova
🇺🇸Cordova, Tennessee, United States
Site 11: Montreal Neurological Institute and Hospital (McGill University)
🇨🇦Montréal, Quebec, Canada
Site 136: General Hanamaki Hospital
🇯🇵Iwata, Japan
Site 214: AmiCare Centrum Medyczne
🇵🇱Łódź, Lódzkie, Poland
Site 192: Krakowski Szpital Specjalistyczny im. Jana Pawła II
🇵🇱Kraków, Malopolskie, Poland
Site 201: Centrum Medyczne Pratia - Warszawa
🇵🇱Warszawa, Mazowieckie, Poland
Site 27: George Washington University
🇺🇸Washington, District of Columbia, United States
Site 179: Kagawa University Hospital - Collagen disease/Rheumatic int
🇯🇵Kita-gun, Japan
Site 146: Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Site 144: Sendai Medical Center
🇯🇵Sendai, Japan
Site 141: Keio University Hospital
🇯🇵Tokyo, Japan
Site 194: Twoja Przychodnia - Centrum Medyczne Nowa Sól
🇵🇱Nowa Sól, Lubuskie, Poland
Site 131: Austin Neuromuscular Center
🇺🇸Austin, Texas, United States
Site 24: Yale University
🇺🇸New Haven, Connecticut, United States
Site 22: University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Site 128: Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Site 176: Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States