Safety and Efficacy Study of Ravulizumab in Adults With Generalized Myasthenia Gravis

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Ravulizumab in Complement-Inhibitor-Naïve Adult Patients With Generalized Myasthenia Gravis

The primary purpose of this study is to evaluate the safety and efficacy of ravulizumab for the treatment of participants with generalized myasthenia gravis (gMG).

Study Overview

• Status: Completed
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Biological: Ravulizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Research Site
    • Toronto, Ontario, Canada, M5G 2C4
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Ostrava, Czechia, 708 52
    • Research Site
  • Praha, Czechia, 12800
    • Research Site
• Denmark
  • Arhus C, Denmark, 8000
    • Research Site
  • Copenhagen, Denmark, 2100
    • Research Site
  • Ålborg, Denmark, 9100
    • Research Site
• France
  • Garches, France, 92380
    • Research Site
  • Lille, France, 59037
    • Research Site
  • Marseille, France, 13005
    • Research Site
  • Nice, France, 6000
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Hamburg, Germany, 20246
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • Münster, Germany, 48149
    • Research Site
  • Würzburg, Germany, 97070
    • Research Site
• Israel
  • Haifa, Israel, 3109601
    • Research Site
  • Tel Aviv, Israel, 6423906
    • Research Site
• Italy
  • Bergamo, Italy, 24127
    • Research Site
  • Bologna, Italy, 40139
    • Research Site
  • Milano, Italy, 20133
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Rome, Italy, 00189
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8655
    • Research Site
  • Chiba-shi, Japan, 260-0877
    • Research Site
  • Fukuoka City, Japan, 812-8582
    • Research Site
  • Hanamaki-shi, Japan, 025-0075
    • Research Site
  • Kawagoe-shi, Japan, 350-8550
    • Research Site
  • Moriguchi-shi, Japan, 570-8507
    • Research Site
  • Nagoya-shi, Japan, 466-8560
    • Research Site
  • Niigata-shi, Japan, 951-8585
    • Research Site
  • Osaka, Japan, 565-0871
    • Research Site
  • Sapporo-shi, Japan, 060-8543
    • Research Site
  • Sapporo-shi, Japan, 063-0005
    • Research Site
  • Sendai-shi, Japan, 983-0045
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site
  • Ube-shi, Japan, 755-8505
    • Research Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 02841
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Seoul, Korea, Republic of, 143-729
    • Research Site
  • Yangsan-si, Korea, Republic of, 50612
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
  • Leiden, Netherlands, 2333 ZA
    • Research Site
• Portugal
  • Porto, Portugal, 4099-001
    • Research Site
• Spain
  • Barcelona, Spain, 08025
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08907
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Murcia, Spain, 30120
    • Research Site
• Switzerland
  • Zürich, Switzerland, 8091
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Research Site
    • Phoenix, Arizona, United States, 85013
      • Research Site
    • Phoenix, Arizona, United States, 85028
      • Research Site
  • California
    • Irvine, California, United States, 92617
      • Research Site
    • Loma Linda, California, United States, 92354
      • Research Site
    • Palo Alto, California, United States, 94304
      • Research Site
    • San Francisco, California, United States, 94115
      • Research Site
    • Sylmar, California, United States, 91342
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
    • Colorado Springs, Colorado, United States, 80907
      • Research Site
    • Fort Collins, Colorado, United States, 80528
      • Research Site
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Research Site
    • Tampa, Florida, United States, 33612
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
    • Rolling Meadows, Illinois, United States, 60008
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Research Site
    • Burlington, Massachusetts, United States, 01805
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
    • East Lansing, Michigan, United States, 48824
      • Research Site
    • Grand Rapids, Michigan, United States, 49525
      • Research Site
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Research Site
    • Las Vegas, Nevada, United States, 89145
      • Research Site
  • New York
    • Great Neck, New York, United States, 11021
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
    • Charlotte, North Carolina, United States, 28207
      • Research Site
    • Durham, North Carolina, United States, 27710
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Research Site
    • Cleveland, Ohio, United States, 44195
      • Research Site
    • Columbus, Ohio, United States, 43221
      • Research Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site
    • North Charleston, South Carolina, United States, 29406
      • Research Site
  • Texas
    • Austin, Texas, United States, 78756
      • Research Site
    • Dallas, Texas, United States, 75206
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • Round Rock, Texas, United States, 78681
      • Research Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with Myasthenia Gravis at least 6 months (180 days) prior to the date of the Screening Visit as confirmed by specific criteria.
2. Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening.
3. MG-ADL profile must be ≥ 6 at screening and randomization (Day 1).
4. Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug to reduce the risk of meningococcal infection (N meningitidis).

Exclusion Criteria:

Medical Conditions

1. Any active or untreated thymoma. History of thymic carcinoma or thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before screening.
2. History of thymectomy within the 12 months prior to screening.
3. History of N meningitidis infection.

4. Use of the following within the time period specified below:

   • IV immunoglobulin within 4 weeks of randomization
   • Use of plasma exchange within 4 weeks of randomization
   • Use of rituximab within 6 months of screening
5. Participants who have received previous treatment with complement inhibitors (for example, eculizumab).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ravulizumab; Participants will receive ravulizumab for the duration of the study.	Biological: Ravulizumab; Concentrated sterile, preservative-free aqueous solution (10 milligrams [mg]/milliliter [mL]) in single-use, 30-mL vial for intravenous (IV) infusion. Single loading dose on Day 1, followed by regular maintenance dosing beginning on Day 15, based on weight.; Other Names: Ultomiris; ALXN1210
Placebo Comparator: Placebo; Participants will receive placebo during the 26-week randomized-controlled period of the study, after which they will enter the open-label extension period of the study and receive ravulizumab.	Drug: Placebo; Matching, sterile, preservative-free aqueous solution in single-use, 30-mL vial for IV infusion. Single loading dose on Day 1, followed by regular maintenance dosing beginning on Day 15, based on weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In Myasthenia Gravis-Activities Of Daily Living (MG-ADL) Total Score At Week 26	The MG-ADL is an 8-point questionnaire that focused on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MGADL questionnaire were derived from symptom-based components of the original 13-item QMG scale to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response was graded 0 (normal) to 3 (most severe). The range of total MG-ADL score was 0 to 24. A decrease in score indicated improvement. Estimates were based on Mixed Effect Repeated Measures (MMRM) that included treatment group, stratification factor region, and MG-ADL total score at baseline, study visit, and study visit by treatment group interaction.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In The Quantitative Myasthenia Gravis (QMG) Total Score At Week 26	The QMG scoring system consisted of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item); each graded 0 to 3, with 3 being the most severe. The range of total QMG score is 0 to 39. The QMG scoring system was considered to be an objective evaluation of therapy for MG and was based on quantitative testing of sentinel muscle groups. A decrease in score indicated improvement. Estimates were based on MMRM that included treatment group, stratification factor region, and QMG total score at baseline, study visit, and study visit by treatment group interaction.	Baseline, Week 26
Percentage of Participants With a Quantitative Myasthenia Gravis (QMG) Total Score Reduction of at Least 5 Points At Week 26	The QMG scoring system consisted of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item); each graded 0 to 3, with 3 being the most severe. The range of total QMG score is 0 to 39. A decrease in score indicated improvement. Percentage of participants with a ≥5-point reduction in the QMG total score are reported. Estimates were based on a generalized linear mixed model (GLMM) that included treatment group, stratification factor region and QMG total score at baseline, study visit and study visit by treatment group interaction.	Week 26
Change From Baseline in Neurological Quality of Life (Neuro-QoL) Fatigue Score at Week 26	The Neuro-QOL Fatigue is a reliable and validated brief 19-item survey of fatigue, completed by the participant. Each items was rated on a scale of 1 to 5, with 5 being the most severe. The range of total score is 19 to 95. Higher scores indicated greater fatigue and greater impact of MG on activities. Estimates were based on MMRM that included treatment group, stratification factor region and Neuro-QoL Fatigue score at baseline, study visit, and study visit by treatment group interaction.	Baseline, Week 26
Percentage of Participants With a Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score Reduction of at Least 3 Points At Week 26	The MG-ADL is an 8-point questionnaire that focused on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MGADL questionnaire were derived from symptom-based components of the original 13-item QMG scale to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response was graded 0 (normal) to 3 (most severe). The range of total MG-ADL score was 0 to 24. A decrease in score indicated improvement. Percentage of participants with a ≥3-point reduction in the MG-ADL total score are reported. Estimates were based on a GLMM that included treatment group, stratification factor region and MG-ADL total score at baseline, study visit and study visit by treatment group interaction.	Week 26
Change From Baseline In the Revised 15 Component Myasthenia Gravis Quality of Life (MG-QOL15r) At Week 26	The revised Myasthenia Gravis Qualify of Life 15-item scale (MG-QOL15r) is a health-related QoL evaluative instrument specific to participants with MG. The MG-QOL15r was designed to provide information about participants' perception of impairment and disability, determine the degree to which disease manifestations are tolerated, and to be administered and interpreted easily. Each item was graded on a scale of 0 to 2, with 2 being the most severe. The range of MG-QOL15r score is 0 to 30. Higher scores indicated greater extent of and dissatisfaction with MG-related dysfunction. Estimates are based on MMRM that included treatment group, stratification factor region and MG-QOL15r score at baseline, study visit and study visit by treatment group interaction.	Baseline, Week 26

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): May 11, 2021
• Study Completion (Actual): May 25, 2023

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): May 28, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Ravulizumab
• Other Study ID Numbers: ALXN1210-MG-306; 2018-003243-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No