Study of ALXN2050 in Adult Participants With Generalized Myasthenia Gravis

Phase 2

Terminated

Conditions: Generalized Myasthenia Gravis
Myasthenia Gravis

Interventions: Drug: ALXN2050
Drug: Placebo

Registration Number: NCT05218096

Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 70

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:
1. Positive serologic test for anti AChR antibodies at the Screening Visit, and
2. Abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation, or
3. Positive response to an AChEI test (eg, edrophonium chloride test), or
4. 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.

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:
1. Intravenous immunoglobulin G or subcutaneous immunoglobulin within the 4 weeks (28 days) prior to the Screening Visit.
2. Use of tacrolimus or cyclosporine within the 4 weeks (28 days) prior to the Screening Visit.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALXN2050: 180 mg	ALXN2050	Participants will receive ALXN2050.
Placebo	Placebo	Participants will receive placebo followed by ALXN2050.
ALXN2050: 120 mg	ALXN2050	Participants will receive ALXN2050.

Primary Outcome Measures

Name	Time	Method
Percentage 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	The MG-ADL profile is an 8-item participant-reported scale that focuses on relevant symptoms and functional performance of ADL in participants with MG. The 8 items of the MG-ADL 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 of MG. Each response is graded 0 (normal) to 3 (most severe). The MG-ADL total score was calculated as the sum of the scores of the 8 items and ranges from 0 to 24, with higher scores indicating worse function.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline In Quantitative Myasthenia Gravis (QMG) Total Score At Week 8	Baseline, Week 8	The QMG Score for Disease Severity is an objective evaluation of therapy for MG and is based on quantitative testing of sentinel muscle groups. The QMG instrument consists 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 QMG total score was calculated as the sum of the scores of the 13 items and ranges from 0 to 39, with higher scores indicating more severe disease. Baseline score at each timepoint as the response variable, treatment group, study visit, and treatment-by-study visit interaction as fixed categorical effects, and baseline QMG total score as a covariate were used to calculate the least square (LS) mean and the standard error.
Change From Baseline In MG-ADL Total Score At Week 8	Baseline, Week 8	The MG-ADL profile is an 8-item participant-reported scale that focuses on relevant symptoms and functional performance of ADL in participants with MG. The 8 items of the MG-ADL 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 of MG. Each response is graded 0 (normal) to 3 (most severe). The MG-ADL total score was calculated as the sum of the scores of the 8 items and ranges from 0 to 24, with higher scores indicating worse function. Baseline score at each timepoint as the response variable, treatment group, study visit, and treatment-by-study visit interaction as fixed categorical effects, and baseline MG-ADL total score as a covariate were used to calculate the LS mean and the standard error.
Change From Baseline In Quality Of Life In Neurological Disorders (Neuro-QoL) Fatigue Score At Week 8	Baseline, Week 8	The Neuro-QoL Fatigue questionnaire is a reliable and validated brief 19-item survey of fatigue, completed by the participant. Each item is scored on a scale of 1-5, with 1 indicating "never" and 5 indicating "sometimes". The Neuro-QoL Fatigue score was calculated as the sum of the scores of the 19 items and ranges from 19-95, with higher scores indicating greater fatigue and greater impact of MG on activities. Baseline score at each timepoint as the response variable, treatment group, study visit, and treatment-by-study visit interaction as fixed categorical effects, and baseline Neuro-QoL Fatigue score as a covariate were used to calculate the LS mean and the standard error.