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 26, 2019
• Est. completion date: May 25, 2023

Study information

• Verified date: August 2023
• Source: Alexion
• 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: 18 Years 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	Clinical Trial Site	Wien
Canada	Clinical Trial Site	Calgary	Alberta
Canada	Clinical Trial Site	Edmonton	Alberta
Canada	Clinical Trial Site	London	Ontario
Canada	Clinical Trial Site	Montreal
Canada	Clinical Trial Site	Toronto	Ontario
Czechia	Clinical Trial Site	Brno
Czechia	Clinical Trial Site	Ostrava	Moravian-Silesian
Czechia	Clinical Trial Site	Prague
Czechia	Clinical Trial Site	Prague	Czech Republic
Denmark	Clinical Trial Site	Aalborg	North Jutland Region
Denmark	Clinical Trial Site	Aarhus N	Jutland
Denmark	Clinical Trial Site	Copenhagen	Hovedstaden
France	Clinical Trial Site	Garches
France	Clinical Trial Site	Lille	Cedex
France	Clinical Trial Site	Marseille	Provence-Alpes-Cote d'Azur
France	Clinical Trial Site	Nice	Provence-Alpes-Cote d'Azur
Germany	Clinical Trial Site	Berlin
Germany	Clinical Trial Site	Essen	Nordrhein-Westfalen
Germany	Clinical Trial Site	Halle	Sachsen-Anhalt
Germany	Clinical Trial Site	Hamburg
Germany	Clinical Trial Site	Hannover
Germany	Clinical Trial Site	Leipzig	Saxony
Germany	Clinical Trial Site	Münster	Nordrhein-Westfalen
Germany	Clinical Trial Site	Würzburg	Bavaria
Israel	Clinical Trial Site	Haifa	Hefa
Israel	Clinical Trial Site	Tel Aviv-Yafo	Tel-Aviv
Italy	Clinical Trial Site	Bergamo	Roma
Italy	Clinical Trial Site	Bologna	Emilia-Romagna
Italy	Clinical Trial Site	Genova	Genoa
Italy	Clinical Trial Site	Messina	Sicilia
Italy	Clinical Trial Site	Milan	Lombardia
Italy	Clinical Trial Site	Rome	Roma
Italy	Clinical Trial Site	Rome	Roma
Japan	Clinical Trial Site	Bunkyo-Ku	Tokyo
Japan	Clinical Trial Site	Bunkyo-Ku	Tokyo
Japan	Clinical Trial Site	Chuo Ku	Chiba
Japan	Clinical Trial Site	Fukuoka-shi	Fukuoka
Japan	Clinical Trial Site	Hanamaki-shi
Japan	Clinical Trial Site	Izumi-Shi	Osaka
Japan	Clinical Trial Site	Kanazawa-shi	Ishikawa
Japan	Clinical Trial Site	Kawagoe-shi	Saitama
Japan	Clinical Trial Site	Moriguchi-shi	Osaka
Japan	Clinical Trial Site	Nagasaki-shi	Nagasaki
Japan	Clinical Trial Site	Nagoya-shi	Aichi
Japan	Clinical Trial Site	Niigata-shi	Niigata
Japan	Clinical Trial Site	Osaka Sayama-shi	Osaka
Japan	Clinical Trial Site	Sapporo-shi	Sapporo
Japan	Clinical Trial Site	Sapporo-shi	Hokkaido
Japan	Clinical Trial Site	Sendai-shi	Miyagi
Japan	Clinical Trial Site	Shinjuku-Ku	Tokyo
Japan	Clinical Trial Site	Suita-shi	Osaka
Japan	Clinical Trial Site	Tokyo
Japan	Clinical Trial Site	Toyonaka-shi	Osaka
Japan	Clinical Trial Site	Ube-shi	Yamaguchi
Korea, Republic of	Clinical Trial Site	Daegu
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Yangsan	Gyeongsangnam-do
Netherlands	Clinical Trial Site	Amsterdam	Noord-Holland
Netherlands	Clinical Trial Site	Leiden	Noord-Holland
Portugal	Clinical Trial Site	Porto
Spain	Clinical Trial Site	Barakaldo	Bizkaia
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Murcia
Spain	Clinical Trial Site	Valencia
Switzerland	Clinical Trial Site	Zürich
United States	Clinical Trial Site	Atlanta	Georgia
United States	Clinical Trial Site	Augusta	Georgia
United States	Clinical Trial Site	Aurora	Colorado
United States	Clinical Trial Site	Austin	Texas
United States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Burlington	Massachusetts
United States	Clinical Trial Site	Burlington	Vermont
United States	Clinical Trial Site	Chapel Hill	North Carolina
United States	Clinical Trial Site	Charleston	South Carolina
United States	Clinical Trial Site	Charleston	South Carolina
United States	Clinical Trial Site	Charlotte	North Carolina
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Cincinnati	Ohio
United States	Clinical Trial Site	Clearwater	Florida
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Colorado Springs	Colorado
United States	Clinical Trial Site	Columbia	Missouri
United States	Clinical Trial Site	Columbus	Ohio
United States	Clinical Trial Site	Columbus	Ohio
United States	Clinical Trial Site	Cordova	Tennessee
United States	Clinical Trial Site	Dallas	Texas
United States	Clinical Trial Site	Detroit Lakes	Minnesota
United States	Clinical Trial Site	Durham	North Carolina
United States	Clinical Trial Site	East Lansing	Michigan
United States	Clinical Trial Site	East Setauket	New York
United States	Clinical Trial Site	Fairway	Kansas
United States	Clinical Trial Site	Fort Collins	Colorado
United States	Clinical Trial Site	Grand Rapids	Michigan
United States	Clinical Trial Site	Great Neck	New York
United States	Clinical Trial Site	Hershey	Pennsylvania
United States	Clinical Trial Site	Houston	Texas
United States	Clinical Trial Site	Indianapolis	Indiana
United States	Clinical Trial Site	Jacksonville	Florida
United States	Clinical Trial Site	Las Vegas	Nevada
United States	Clinical Trial Site	Las Vegas	Nevada
United States	Clinical Trial Site	Lexington	Kentucky
United States	Clinical Trial Site	Lexington	Kentucky
United States	Clinical Trial Site	Loma Linda	California
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Milwaukee	Wisconsin
United States	Clinical Trial Site	Morgantown	West Virginia
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	New Haven	Connecticut
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Orange	California
United States	Clinical Trial Site	Palo Alto	California
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Phoenix	Arizona
United States	Clinical Trial Site	Phoenix	Arizona
United States	Clinical Trial Site	Phoenix	Arizona
United States	Clinical Trial Site	Richmond	Virginia
United States	Clinical Trial Site	Rolling Meadows	Illinois
United States	Clinical Trial Site	Round Rock	Texas
United States	Clinical Trial Site	Saint Louis	Missouri
United States	Clinical Trial Site	San Antonio	Texas
United States	Clinical Trial Site	San Francisco	California
United States	Clinical Trial Site	Seattle	Washington
United States	Clinical Trial Site	Springfield	Oregon
United States	Clinical Trial Site	Sylmar	California
United States	Clinical Trial Site	Tampa	Florida
United States	Clinical Trial Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Alexion

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