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

Generalized Myasthenia Gravis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03920293
• Other study ID #: ALXN1210-MG-306
• Secondary ID: 2018-003243-39
• Status: Completed
• Phase: Phase 3
• Start date: March 12, 2019
• Est. completion date: May 25, 2023

Study information

• Verified date: April 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: May 25, 2023
• Est. primary completion date: May 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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).

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

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.

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.

Locations

Country	Name	City	State
Austria	Research Site	Vienna
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Czechia	Research Site	Brno
Czechia	Research Site	Ostrava
Czechia	Research Site	Praha
Denmark	Research Site	Ålborg
Denmark	Research Site	Arhus C
Denmark	Research Site	Copenhagen
France	Research Site	Garches
France	Research Site	Lille
France	Research Site	Marseille
France	Research Site	Nice
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Hamburg
Germany	Research Site	Leipzig
Germany	Research Site	Münster
Germany	Research Site	Würzburg
Israel	Research Site	Haifa
Israel	Research Site	Tel Aviv
Italy	Research Site	Bergamo
Italy	Research Site	Bologna
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Roma
Italy	Research Site	Rome
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-shi
Japan	Research Site	Fukuoka City
Japan	Research Site	Hanamaki-shi
Japan	Research Site	Kawagoe-shi
Japan	Research Site	Moriguchi-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Ube-shi
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Yangsan-si
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Leiden
Portugal	Research Site	Porto
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Murcia
Switzerland	Research Site	Zürich
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Burlington	Massachusetts
United States	Research Site	Burlington	Vermont
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbia	Missouri
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Durham	North Carolina
United States	Research Site	East Lansing	Michigan
United States	Research Site	Fairfield	Connecticut
United States	Research Site	Fort Collins	Colorado
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Great Neck	New York
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Irvine	California
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kansas City	Kansas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lexington	Kentucky
United States	Research Site	Loma Linda	California
United States	Research Site	Morgantown	West Virginia
United States	Research Site	New York	New York
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Palo Alto	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Richmond	Virginia
United States	Research Site	Rolling Meadows	Illinois
United States	Research Site	Round Rock	Texas
United States	Research Site	San Francisco	California
United States	Research Site	Sylmar	California
United States	Research Site	Tampa	Florida
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Czechia,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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