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

NCT03920293 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ALXN1210-MG-3062018-003243-39
• Study Type: interventional
• Target: 175
• Locations: 15 countries
• Sites: 106

Brief Summary

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).

Conditions

Generalized Myasthenia Gravis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change From Baseline In The Quantitative Myasthenia Gravis (QMG) Total Score At Week 26

  Baseline, Week 26

• Percentage of Participants With a Quantitative Myasthenia Gravis (QMG) Total Score Reduction of at Least 5 Points At Week 26

  Week 26

• Change From Baseline In the Revised 15 Component Myasthenia Gravis Quality of Life (MG-QOL15r) At Week 26

  Baseline, Week 26

• Change From Baseline in Neurological Quality of Life (Neuro-QoL) Fatigue Score at Week 26

  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

  Week 26

Study Arms (2)

Ravulizumab

EXPERIMENTAL

Participants will receive ravulizumab for the duration of the study.

Biological: Ravulizumab

Placebo

PLACEBO COMPARATOR

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

Interventions

Ravulizumab BIOLOGICAL

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.

Also known as: ALXN1210, Ultomiris

Ravulizumab

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with Myasthenia Gravis at least 6 months (180 days) prior to the date of the Screening Visit as confirmed by specific criteria.
• Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening.
• MG-ADL profile must be ≥ 6 at screening and randomization (Day 1).
• 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).

You may not qualify if:

• Medical Conditions
• 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.
• History of thymectomy within the 12 months prior to screening.
• History of N meningitidis infection.
• 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
• Participants who have received previous treatment with complement inhibitors (for example, eculizumab).

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (106)

Research Site

Phoenix, Arizona, 85013, United States

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Phoenix, Arizona, 85018, United States

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Phoenix, Arizona, 85028, United States

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Irvine, California, 92617, United States

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Loma Linda, California, 92354, United States

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Palo Alto, California, 94304, United States

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San Francisco, California, 94115, United States

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Sylmar, California, 91342, United States

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Aurora, Colorado, 80045, United States

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Colorado Springs, Colorado, 80907, United States

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Fort Collins, Colorado, 80528, United States

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Fairfield, Connecticut, 06824, United States

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Washington D.C., District of Columbia, 20007, United States

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Jacksonville, Florida, 32209, United States

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Tampa, Florida, 33612, United States

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Chicago, Illinois, 60637, United States

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Rolling Meadows, Illinois, 60008, United States

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Indianapolis, Indiana, 46202, United States

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Kansas City, Kansas, 66160, United States

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Lexington, Kentucky, 40503, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02116, United States

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Burlington, Massachusetts, 01805, United States

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Ann Arbor, Michigan, 48109, United States

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East Lansing, Michigan, 48824, United States

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Grand Rapids, Michigan, 49525, United States

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Columbia, Missouri, 65201, United States

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Las Vegas, Nevada, 89104, United States

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Las Vegas, Nevada, 89145, United States

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Great Neck, New York, 11021, United States

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New York, New York, 10021, United States

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Chapel Hill, North Carolina, 27599, United States

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Charlotte, North Carolina, 28207, United States

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Durham, North Carolina, 27710, United States

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Cincinnati, Ohio, 45219, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43221, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Charleston, South Carolina, 29425, United States

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North Charleston, South Carolina, 29406, United States

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Austin, Texas, 78756, United States

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Dallas, Texas, 75206, United States

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Houston, Texas, 77030, United States

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Round Rock, Texas, 78681, United States

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Burlington, Vermont, 05401, United States

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Richmond, Virginia, 23298, United States

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Morgantown, West Virginia, 26506, United States

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Vienna, 1090, Austria

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Edmonton, Alberta, T6G 2G3, Canada

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London, Ontario, N6A 5A5, Canada

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Toronto, Ontario, M5G 2C4, Canada

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Montreal, Quebec, H3A 2B4, Canada

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Brno, 625 00, Czechia

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Ostrava, 708 52, Czechia

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Prague, 12800, Czechia

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Aalborg, 9100, Denmark

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Arhus C, 8000, Denmark

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Copenhagen, 2100, Denmark

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Garches, 92380, France

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Lille, 59037, France

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Marseille, 13005, France

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Nice, 6000, France

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Berlin, 10117, Germany

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Essen, 45147, Germany

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Hamburg, 20246, Germany

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Leipzig, 04103, Germany

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Münster, 48149, Germany

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Würzburg, 97070, Germany

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Haifa, 3109601, Israel

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Tel Aviv, 6423906, Israel

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Bergamo, 24127, Italy

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Bologna, 40139, Italy

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Milan, 20133, Italy

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Napoli, 80131, Italy

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Roma, 00168, Italy

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Rome, 00189, Italy

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Bunkyō City, 113-8655, Japan

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Chiba, 260-0877, Japan

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Fukuoka, 812-8582, Japan

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Hanamaki-shi, 025-0075, Japan

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Kawagoe-shi, 350-8550, Japan

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Moriguchi-shi, 570-8507, Japan

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Nagoya, 466-8560, Japan

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Niigata, 951-8585, Japan

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Osaka, 565-0871, Japan

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Sapporo, 060-8543, Japan

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Sapporo, 063-0005, Japan

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Sendai, 983-0045, Japan

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Shinjuku-ku, 160-8582, Japan

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Ube-shi, 755-8505, Japan

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Amsterdam, 1105 AZ, Netherlands

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Leiden, 2333 ZA, Netherlands

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Porto, 4099-001, Portugal

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Daegu, 41404, South Korea

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Seoul, 02841, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Seoul, 143-729, South Korea

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Yangsan, 50612, South Korea

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Barcelona, 08025, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Madrid, 28040, Spain

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Murcia, 30120, Spain

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Zurich, 8091, Switzerland

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Related Publications (4)

• Vu T, Meisel A, Mantegazza R, Annane D, Katsuno M, Aguzzi R, Enayetallah A, Beasley KN, Rampal N, Howard JF. Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis. NEJM Evid. 2022 May;1(5):EVIDoa2100066. doi: 10.1056/EVIDoa2100066. Epub 2022 Apr 26.

  PMID: 38319212 DERIVED

• Meisel A, Annane D, Vu T, Mantegazza R, Katsuno M, Aguzzi R, Frick G, Gault L, Howard JF Jr; CHAMPION MG Study Group. Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension. J Neurol. 2023 Aug;270(8):3862-3875. doi: 10.1007/s00415-023-11699-x. Epub 2023 Apr 27.

  PMID: 37103755 DERIVED

• Vu T, Ortiz S, Katsuno M, Annane D, Mantegazza R, Beasley KN, Aguzzi R, Howard JF Jr. Ravulizumab pharmacokinetics and pharmacodynamics in patients with generalized myasthenia gravis. J Neurol. 2023 Jun;270(6):3129-3137. doi: 10.1007/s00415-023-11617-1. Epub 2023 Mar 9.

  PMID: 36890354 DERIVED

• Vanoli F, Mantegazza R. Ravulizumab for the treatment of myasthenia gravis. Expert Opin Biol Ther. 2023 Mar;23(3):235-241. doi: 10.1080/14712598.2023.2185131. Epub 2023 Mar 8.

  PMID: 36852670 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

ravulizumab

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: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

+1 855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All investigative site personnel, sponsor staff, sponsor designees, staff directly associated with the conduct of the study, and all participants will be blinded to treatment assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 18, 2019
• Study Start: March 12, 2019
• Primary Completion: May 11, 2021
• Study Completion: May 25, 2023
• Last Updated: May 28, 2024
• Results First Posted: May 26, 2022

Record last verified: 2024-04

Locations

AU (1); NL (2); CA (4); CZ (3); PT (1); CH (1); US (49); JP (14); ES (4); DK (3); IL (2); FR (4); IT (6); KR (6); DE (6)