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

NCT04115293 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RA101495-02.301
• Study Type: interventional
• Target: 174
• Locations: 10 countries
• Sites: 77

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.

Conditions

Myasthenia Gravis, Generalized

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Total Score

  From Baseline to End of Treatment (Week 12)

• Change From Baseline to Week 12 in the Myasthenia Gravis Composite (MGC) Scale Total Score

  From Baseline to End of Treatment (Week 12)

• 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)

• Time to First Receipt of Rescue Therapy Over the 12-week Treatment Period

  From Baseline to End of Treatment (Week 12)

• Percentage of Participants Achieving Minimal Symptom Expression (MSE) at Week 12 Without Rescue Therapy

  End of Treatment (Week 12)

Study Arms (2)

0.3 mg/kg zilucoplan (RA101495)

EXPERIMENTAL

Drug: zilucoplan (RA101495)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

zilucoplan (RA101495) DRUG

Daily subcutaneous (SC) injection

0.3 mg/kg zilucoplan (RA101495)

Placebo DRUG

Daily subcutaneous (SC) injection

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ra Pharmaceuticals, Inc.: lead

Study Sites (77)

Site 41: Diagnostic and Medical Clinic

Mobile, Alabama, 36604, United States

Location

Site 116: Neuromuscular Clinic and Research Center

Phoenix, Arizona, 85028, United States

Location

Site 4: University of Southern California

Los Angeles, California, 90033, United States

Location

Site 31: University of California Irvine

Orange, California, 92868, United States

Location

Site 220: Investigator Site

Pasadena, California, 91101, United States

Location

Site 160: Forbes Norris MDA/ALS Research and Treatment Center

San Francisco, California, 94115, United States

Location

Site 24: Yale University

New Haven, Connecticut, 06510, United States

Location

Site 27: George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Site 182: Gelasio Baras Neurology

Miami, Florida, 33175, United States

Location

Site 25: University of South Florida

Tampa, Florida, 33612, United States

Location

Site 135: Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Site 176: Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Site 188: North Shore Medical Group - Glenview

Glenview, Illinois, 60026-1339, United States

Location

Site 156: Indiana University Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

Site 32: Kansas University Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

Site 221: Neurology Center of New England

Foxborough, Massachusetts, 02035, United States

Location

Site 33: Detroit medical Center - University Health Center

Detroit, Michigan, 48202, United States

Location

Site 49: Michigan State University

East Lansing, Michigan, 48824, United States

Location

Site 127: University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Site 134: Neurology and Sleep Disorders Clinic

Columbia, Missouri, 65212, United States

Location

Site 117: Las Vegas Clinic

Las Vegas, Nevada, 89145, United States

Location

Site 123: Northwell Health Neuroscience Institute

Great Neck, New York, 11021, United States

Location

Site 23: Hospital for Special Surgery

New York, New York, 10021, United States

Location

Site 47: Mount Sinai Hospital

New York, New York, 10029, United States

Location

Site 22: University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Site 15: Duke University

Durham, North Carolina, 27710, United States

Location

Site 122: Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Site 38: Ohio State University

Columbus, Ohio, 43210, United States

Location

Site 40: Allegheny Neurological Associates

Pittsburgh, Pennsylvania, 15212, United States

Location

Site 128: Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Site 185: Neurology Clinic Cordova

Cordova, Tennessee, 38018, United States

Location

Site 131: Austin Neuromuscular Center

Austin, Texas, 78756, United States

Location

Site 19: University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Site 39: University of Utah

Salt Lake City, Utah, 84132, United States

Location

Site 164: University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Site 154: University of Washington

Seattle, Washington, 98195, United States

Location

Site 45: Center for Neurological Disorders

Milwaukee, Wisconsin, 53215, United States

Location

Site 44: London Health Sciences Centre University Hospital

London, Ontario, N6A 5A5, Canada

Location

Site 11: Montreal Neurological Institute and Hospital (McGill University)

Montreal, Quebec, H3A 2B4, Canada

Location

Site 191: Centre Hosptitalier Universitaire d'Angers

Angers, France

Location

Site 204: Centre Hospitalier Régional Universitaire de Lille

Lille, France

Location

Site 118: Hôpital Pasteur

Nice, 06000, France

Location

Site 105: Pitié-Salpêtrière University Hospital

Paris, 75013, France

Location

Site 137: Les Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Site 150: Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Site 129: Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Site 126: Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Site 132: Università Cattolica del Sacro Cuore - Campus di Milano

Roma, 20123, Italy

Location

Site 169: International University of Health and Welfare Narita Hospital

Narita, Chiba, 286-8520, Japan

Location

Site 151: Chiba University Hospital

Chiba, 260-8677, Japan

Location

Site 136: General Hanamaki Hospital

Iwata, 025-0075, Japan

Location

Site 179: Kagawa University Hospital - Collagen disease/Rheumatic int

Kita-gun, Japan

Location

Site 146: Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

Site 152: Hokkaido Medical Center

Sapporo, 063-0005, Japan

Location

Site 144: Sendai Medical Center

Sendai, 983-8520, Japan

Location

Site 153: Toho University Ohashi Medical Center

Tokyo, 153-8515, Japan

Location

Site 163: Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

Location

Site 141: Keio University Hospital

Tokyo, 160-8582, Japan

Location

Site 165: Osaka University Hospital

Tokyo, 565-0871, Japan

Location

Site 140: Haukeland University Hospital / Health Bergen

Bergen, 5021, Norway

Location

Site 143: Oslo Universitetssykehus

Oslo, 0450, Norway

Location

Site 209: Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD

Poznan, Greater Poland Voivodeship, 61-853, Poland

Location

Site 192: Krakowski Szpital Specjalistyczny im. Jana Pawła II

Krakow, Lesser Poland Voivodeship, 31-202, Poland

Location

Site 205: Prywatny Gabinet Lekarski Urszula Chyrchel-Paszkiewicz

Lublin, Lublin Voivodeship, 20-093, Poland

Location

Site 194: Twoja Przychodnia - Centrum Medyczne Nowa Sól

Nowa Sól, Lubusz Voivodeship, 67-100, Poland

Location

Site 214: AmiCare Centrum Medyczne

Lodz, Lódzkie, 90-644, Poland

Location

Site 201: Centrum Medyczne Pratia - Warszawa

Warsaw, Masovian Voivodeship, 01-868, Poland

Location

Site 195: Wielospecjalistyczna Poradnia Lekarska Synapsis

Katowice, Silesian Voivodeship, 40-123, Poland

Location

Site 213: Niepubliczny Zakład Opieki Zdrowotnej NOVO-MED

Katowice, Silesian Voivodeship, 40-650, Poland

Location

Site 193: Krakowska Akademia Neurologii - Centrum Neurologii Kliniczne

Krakow, Poland

Location

Site 211: Specjalistyczne Gabinety Sp. z o.o.

Krakow, Poland

Location

Site 210: Clinhouse Centrum Medyczne

Lublin, 20-093, Poland

Location

Site 133: Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Site 168: Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Site 138: Hospital Universitario de Basurto

Bilbao, 48013, Spain

Location

Site 119: Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

Location

Site 130: Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 37059508 RESULT

• 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.

  PMID: 38400914 RESULT

• 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.

  PMID: 39314260 RESULT

• Hewamadduma C, Freimer M, Genge A, Leite MI, Utsugisawa K, Vu T, Boroojerdi B, Grimson F, Savic N, Vanderkelen M, Howard JF Jr; RAISE-XT study team. Changes in corticosteroid and non-steroidal immunosuppressive therapy with long-term zilucoplan treatment in generalized myasthenia gravis. J Neurol. 2025 Jun 12;272(7):457. doi: 10.1007/s00415-025-13113-0.

  PMID: 40504283 RESULT

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

zilucoplan

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

001 844 599 2273

Study Officials

• UCB Cares

  0018445992273 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 4, 2019
• Study Start: September 17, 2019
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: July 16, 2025
• Results First Posted: January 17, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

PL (11); GB (2); JP (11); IT (2); DE (2); NO (2); ES (3); US (37); CA (2); FR (5)