Study of ALXN2050 in Adult Participants With Generalized Myasthenia Gravis

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of ALXN2050 (120 milligrams [mg], 180 mg) in participants with generalized myasthenia gravis (gMG). Safety will be monitored throughout the study.

Detailed Description
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The study consists of a blinded 8-week Primary Evaluation Period (PEP) and a blinded 26-week Extended Treatment Period (ETP). After completion of 34 weeks of treatment, participants will enter an Open-label Extension (OLE) Period for up to 1.5 years.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Evaluate the Efficacy and Safety of ALXN2050 in Adult Participants With Generalized Myasthenia Gravis

Conditions
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Generalized Myasthenia Gravis, Myasthenia Gravis

Intervention / Treatment
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* Drug: ALXN2050
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosed with MG at least 3 months (90 days) prior to the date of the Screening Visit. Confirmation of MG must be made via the following: Positive serologic test for anti AChR antibodies at the Screening Visit, and Abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation, or Positive response to an AChEI test (eg, edrophonium chloride test), or Improvement of signs or symptoms related to MG during treatment with an oral AChEI, as determined by the treating physician Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at the Screening Visit. MG-ADL total score must be ≥ 5 (with at least 50% of the score attributed to non-ocular elements) at the Screening Visit and at randomization (Day 1). Participants receiving treatment with protocol-specified immunosuppressive therapies, corticosteroids, or acetylcholinesterase inhibitors must have been receiving treatment and on a stable dose prior to the date of the Screening Visit, with no changes to the regimen expected during screening, the PEP, and/or the ETP. Key Exclusion Criteria: Estimated glomerular filtration rate ≤ 30 milliliters/minute/1.73 squared meters during Screening calculated by Chronic Kidney Disease Epidemiology Collaboration. History of thymectomy, thymomectomy, or any other thymic surgery within 12 months prior to the Screening Visit. Any untreated thymic malignancy, carcinoma, or thymoma. Participants with a history of treated thymic malignancy or carcinoma are eligible for enrollment if they meet pre-specified conditions outlined in the protocol. Clinical features consistent with Clinical Deterioration at the time of the Screening Visit or at any time during the Screening Period prior to randomization (Day 1). Use of the following within the time periods specified below: Intravenous immunoglobulin G or subcutaneous immunoglobulin within the 4 weeks (28 days) prior to the Screening Visit. Use of tacrolimus or cyclosporine within the 4 weeks (28 days) prior to the Screening Visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN2050: 180 mg<br>Participants will receive ALXN2050. | Drug: ALXN2050<br>* Oral tablet.<br>* Other names: ACH-0145228 (formerly);|
| Experimental: ALXN2050: 120 mg<br>Participants will receive ALXN2050. | Drug: ALXN2050<br>* Oral tablet.<br>* Other names: ACH-0145228 (formerly);|
| Placebo Comparator: Placebo<br>Participants will receive placebo followed by ALXN2050. | Drug: ALXN2050<br>* Oral tablet.<br>* Other names: ACH-0145228 (formerly);Drug: Placebo<br>* Oral tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion Of Participants With A Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score Reduction Of ≥ 2 Points In Any 4 Consecutive Weeks During The First 8 Weeks And Who Did Not Receive Rescue Therapy |  | Baseline through Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline In Quantitative Myasthenia Gravis (QMG) Total Score At Week 8 |  | Baseline, Week 8 | 
| Proportion Of Participants Meeting Prespecified Threshold In The QMG Total Score At Week 8 |  | Week 8 | 
| Proportion Of Participants Meeting Prespecified Threshold In The QMG Total Score In Any 4 Consecutive Weeks During The First 8 Weeks And Who Did Not Receive Rescue Therapy |  | Baseline through Week 8 | 
| Change From Baseline In MG-ADL Total Score At Week 8 |  | Baseline, Week 8 | 
| Proportion Of Participants Meeting Prespecified Threshold In The MG-ADL Total Score In Any 4 Consecutive Weeks During The First 8 Weeks And Who Did Not Receive Rescue Therapy |  | Baseline through Week 8 | 
| Proportion Of Participants Meeting Prespecified Threshold In The MG-ADL Total Score At Week 8 |  | Week 8 | 
| Change From Baseline In Quality Of Life In Neurological Disorders Fatigue Questionnaire (Neuro-QoL) Fatigue Score At Week 8 |  | Baseline, Week 8 | 
| Maximum Peak Plasma Concentration (Cmax) Of ALXN2050 Over Time |  | Baseline through Week 8 | 
| Pre-dose Concentration (Ctrough) Of ALXN2050 Over Time |  | Baseline through Week 8 | 
| Absolute Values And Change From Baseline In Plasma Concentration Of Bb Fragment Of Complement Factor B At Week 8 |  | Baseline, Week 8 | 
| Absolute Values And Change From Baseline In Serum Alternative Pathway (AP) Activity At Week 8 As Measured By Wieslab Assay |  | Baseline, Week 8 | 
| Plasma Factor D Concentration Over Time |  | Baseline through Week 8 | 
| Serum Complement Component 3 Concentration Over Time |  | Baseline through Week 8 | 
| Serum Classical Pathway Activity Over Time As Measured By CH50 |  | Baseline through Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALXN2050, gMG