Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis

Myasthenia Gravis, Generalized Clinical Trial

— RAISE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04115293
• Other study ID #: RA101495-02.301
• Status: Completed
• Phase: Phase 3
• Start date: September 17, 2019
• Est. completion date: December 30, 2021

Study information

• Verified date: May 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis
• Myasthenia Gravis, Generalized

Intervention

Drug:
• zilucoplan (RA101495)
Daily subcutaneous (SC) injection
• Placebo
Daily subcutaneous (SC) injection

Locations

Country	Name	City	State
Canada	Site 44: London Health Sciences Centre University Hospital	London	Ontario
Canada	Site 11: Montreal Neurological Institute and Hospital (McGill University)	Montréal	Quebec
France	Site 191: Centre Hosptitalier Universitaire d'Angers	Angers Cedex 9
France	Site 204: Centre Hospitalier Régional Universitaire de Lille	Lille
France	Site 118: Hôpital Pasteur	Nice
France	Site 105: Pitié-Salpêtrière University Hospital	Paris
France	Site 137: Les Hôpitaux Universitaires de Strasbourg	Strasbourg
Germany	Site 150: Universitätsmedizin Göttingen	Göttingen
Germany	Site 129: Universitätsklinikum Tübingen	Tübingen
Italy	Site 126: Fondazione IRCCS Istituto Neurologico Carlo Besta	Milan
Italy	Site 132: Università Cattolica del Sacro Cuore - Campus di Milano	Roma
Japan	Site 151: Chiba University Hospital	Chiba
Japan	Site 136: General Hanamaki Hospital	Iwata
Japan	Site 179: Kagawa University Hospital - Collagen disease/Rheumatic int	Kita-gun
Japan	Site 146: Nagasaki University Hospital	Nagasaki
Japan	Site 169: International University of Health and Welfare Narita Hospital	Narita	Chiba
Japan	Site 152: Hokkaido Medical Center	Sapporo
Japan	Site 144: Sendai Medical Center	Sendai
Japan	Site 141: Keio University Hospital	Tokyo
Japan	Site 153: Toho University Ohashi Medical Center	Tokyo
Japan	Site 163: Tokyo Medical University Hospital	Tokyo
Japan	Site 165: Osaka University Hospital	Tokyo
Norway	Site 140: Haukeland University Hospital / Health Bergen	Bergen
Norway	Site 143: Oslo Universitetssykehus	Oslo
Poland	Site 195: Wielospecjalistyczna Poradnia Lekarska Synapsis	Katowice	Slaskie
Poland	Site 213: Niepubliczny Zaklad Opieki Zdrowotnej NOVO-MED	Katowice	Slaskie
Poland	Site 192: Krakowski Szpital Specjalistyczny im. Jana Pawla II	Kraków	Malopolskie
Poland	Site 193: Krakowska Akademia Neurologii - Centrum Neurologii Kliniczne	Kraków
Poland	Site 211: Specjalistyczne Gabinety Sp. z o.o.	Kraków
Poland	Site 214: AmiCare Centrum Medyczne	Lódz	Lódzkie
Poland	Site 205: Prywatny Gabinet Lekarski Urszula Chyrchel-Paszkiewicz	Lublin	Lubelskie
Poland	Site 210: Clinhouse Centrum Medyczne	Lublin
Poland	Site 194: Twoja Przychodnia - Centrum Medyczne Nowa Sól	Nowa Sól	Lubuskie
Poland	Site 209: Niepubliczny Zaklad Opieki Zdrowotnej NEURO - KARD	Poznan	Wielkopolskie
Poland	Site 201: Centrum Medyczne Pratia - Warszawa	Warszawa	Mazowieckie
Spain	Site 133: Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Site 168: Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Site 138: Hospital Universitario de Basurto	Bilbao
United Kingdom	Site 119: Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	Site 130: Royal Hallamshire Hospital	Sheffield
United States	Site 135: Augusta University Medical Center	Augusta	Georgia
United States	Site 131: Austin Neuromuscular Center	Austin	Texas
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 164: University of Virginia Health System	Charlottesville	Virginia
United States	Site 122: Cleveland Clinic	Cleveland	Ohio
United States	Site 134: Neurology and Sleep Disorders Clinic	Columbia	Missouri
United States	Site 38: Ohio State University	Columbus	Ohio
United States	Site 185: Neurology Clinic Cordova	Cordova	Tennessee
United States	Site 19: University of Texas Southwestern	Dallas	Texas
United States	Site 33: Detroit medical Center - University Health Center	Detroit	Michigan
United States	Site 15: Duke University	Durham	North Carolina
United States	Site 49: Michigan State University	East Lansing	Michigan
United States	Site 221: Neurology Center of New England	Foxboro	Massachusetts
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 176: Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Site 156: Indiana University Health Neuroscience Center	Indianapolis	Indiana
United States	Site 156: University of Kansas Medical Center	Kansas City	Kansas
United States	Site 32: Kansas University Medical Center Research Institute	Kansas City	Kansas
United States	Site 117: Las Vegas Clinic	Las Vegas	Nevada
United States	Site 4: University of Southern California	Los Angeles	California
United States	Site 182: Gelasio Baras Neurology	Miami	Florida
United States	Site 45: Center for Neurological Disorders	Milwaukee	Wisconsin
United States	Site 127: University of Minnesota	Minneapolis	Minnesota
United States	Site 41: Diagnostic and Medical Clinic	Mobile	Alabama
United States	Site 24: Yale University	New Haven	Connecticut
United States	Site 23: Hospital for Special Surgery	New York	New York
United States	Site 47: Mount Sinai Hospital	New York	New York
United States	Site 31: University of California Irvine	Orange	California
United States	Site 220: Investigator Site	Pasadena	California
United States	Site 116: Neuromuscular Clinic and Research Center	Phoenix	Arizona
United States	Site 40: Allegheny Neurological Associates	Pittsburgh	Pennsylvania
United States	Site 39: University of Utah	Salt Lake City	Utah
United States	Site 160: Forbes Norris MDA/ALS Research and Treatment Center	San Francisco	California
United States	Site 154: University of Washington	Seattle	Washington
United States	Site 25: University of South Florida	Tampa	Florida
United States	Site 27: George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Ra Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Japan,  Norway,  Poland,  Spain,  United Kingdom, 

References & Publications (1)

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, Lowco — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline (CFB) to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Total Score	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.	From Baseline to End of Treatment (Week 12)
Secondary	Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Total Score	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.	From Baseline to End of Treatment (Week 12)
Secondary	Change From Baseline to Week 12 in the Myasthenia Gravis Composite (MGC) Scale Total Score	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.	From Baseline to End of Treatment (Week 12)
Secondary	Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life Revised (MG-QoL15r) Scale Total Score	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.	From Baseline to End of Treatment (Week 12)
Secondary	Time to First Receipt of Rescue Therapy Over the 12-week Treatment Period	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.	From Baseline to End of Treatment (Week 12)
Secondary	Percentage of Participants Achieving Minimal Symptom Expression (MSE) at Week 12 Without Rescue Therapy	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.	End of Treatment (Week 12)
Secondary	Percentage of Participants Achieving a = 3-point Reduction in MG-ADL Score at Week 12 Without Rescue Therapy	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.	End of Treatment (Week 12)
Secondary	Percentage of Participants Achieving a =5-point Reduction in QMG Score Without Rescue Therapy at 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.	End of Treatment (Week 12)
Secondary	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	From Baseline (Day 1) to Safety Follow-up visit (19 Weeks [12 weeks Treatment Period plus up to 7 weeks Follow-up])