Generalized Myasthenia Gravis Myasthenia Gravis

Primary Outcome Measures : 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 Secondary Outcome Measures : Change From Baseline In Quantitative Myasthenia Gravis (QMG) Total Score At Week 8 [ Time Frame: Baseline, Week 8 ] Proportion Of Participants Meeting Prespecified Threshold In The QMG Total Score At Week 8 [ Time Frame: 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 [ Time Frame: Baseline through Week 8 ] Change From Baseline In MG-ADL Total Score At Week 8 [ Time Frame: 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 [ Time Frame: Baseline through Week 8 ] Proportion Of Participants Meeting Prespecified Threshold In The MG-ADL Total Score At Week 8 [ Time Frame: Week 8 ] Change From Baseline In Quality Of Life In Neurological Disorders Fatigue Questionnaire (Neuro-QoL) Fatigue Score At Week 8 [ Time Frame: Baseline, Week 8 ] Maximum Peak Plasma Concentration (Cmax) Of ALXN2050 Over Time [ Time Frame: Baseline through Week 8 ] Pre-dose Concentration (Ctrough) Of ALXN2050 Over Time [ Time Frame: Baseline through Week 8 ] Absolute Values And Change From Baseline In Plasma Concentration Of Bb Fragment Of Complement Factor B At Week 8 [ Time Frame: Baseline, Week 8 ] Absolute Values And Change From Baseline In Serum Alternative Pathway (AP) Activity At Week 8 As Measured By Wieslab Assay [ Time Frame: Baseline, Week 8 ] Plasma Factor D Concentration Over Time [ Time Frame: Baseline through Week 8 ] Serum Complement Component 3 Concentration Over Time [ Time Frame: Baseline through Week 8 ] Serum Classical Pathway Activity Over Time As Measured By CH50 [ Time Frame: Baseline through Week 8 ]

ALXN2050

ALXN2050

tablet

60 mg/tablet

Proportion of participants with an 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

Age
1. Participant must be at least 18 years of age at the time of signing the informed consent
form (ICF).
Type of Participant and Disease Characteristics
2. Diagnosed with MG at least 3 months (90 days) prior to the date of the Screening Visit.
a. Confirmation of MG must be made via the following:
b. Positive serologic test for anti-AChR antibodies at the Screening Visit, and
c. Abnormal neuromuscular transmission demonstrated by single fiber
electromyography or repetitive nerve stimulation, or
d. Positive response to an AChEI test (eg, edrophonium chloride test), or
e. Improvement of signs or symptoms related to MG during treatment with an oral
AChEI, as determined by the treating physician
3. Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at the
Screening Visit.
4. 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).
Note: Enrollment of participants with MG-ADL total score < 7 will be limited to
approximately 10% of the total enrollment.
5. Participants receiving treatment with any of the following must have been receiving
treatment and on a stable dose for the time periods specified below prior to the date of the
Screening Visit, with no changes to the regimen expected during screening, the PEP,
and/or the ETP:
Sex
6. Male or female participant.
7. Female participants of childbearing potential and male participants must follow
protocol-specified contraception guidance (Section 10.4.2).
Informed Consent
8. Capable of giving signed informed consent as described in Section 10.1.3, which includes
compliance with the requirements and restrictions listed in the ICF and in this protocol.
Other Inclusions
9. Vaccinated against meningococcal infection (Neisseria meningitidis) within 3 years prior
to, or at the time of, randomization (Day 1).
Participants who initiate study intervention less than 2 weeks after receiving a
meningococcal vaccine must receive appropriate prophylactic antibiotics until at least
2 weeks after the vaccination against N meningitidis.

Medical Conditions
1. Any medical condition (eg, cardiac, pulmonary, renal, oncologic, or psychiatric) that, in
the opinion of the Investigator or the Medical Monitor, might interfere with participation
in the study, pose any added risk to the participant, or confound the assessment of the
participant.
2. History of thymectomy, thymomectomy, or any other thymic surgery within 12 months
prior to the Screening Visit.
3. Any untreated thymic malignancy, carcinoma, or thymoma.
Participants with a history of treated thymic malignancy or carcinoma are eligible for
enrollment if they meet the following conditions:
a. Treatment completed > 5 years prior to the Screening Visit
b. No known recurrence within the 5 years prior to the Screening Visit
c. No radiological indication of recurrence in a computed tomography (CT) or magnetic
resonance imaging (MRI) scan, including administration of IV contrast, performed
within 6 months of randomization (Day 1)
Participants with a history of treated benign thymoma are eligible if they meet the
following conditions:
d. Histopathological or equivalent records indicating the diagnosis of benign thymoma
e. Treatment completed > 12 months prior to the Screening Visit
f. No known recurrence within the 12 months prior to the Screening Visit
g. No radiological indication of recurrence in a CT or MRI scan, including
administration of IV contrast, performed within 6 months of randomization (Day 1)
h. If adequate records confirming the diagnosis of benign thymoma are not available,
the participant must satisfy the eligibility criteria for thymic malignancy or carcinoma
stated above.
4. Clinical features that, in the opinion of the Investigator, are consistent with
Clinical Deterioration at the time of the Screening Visit or at any time during the
Screening Period prior to randomization (Day 1).
5. History of seizure.
6. History of N meningitidis infection.
7. Evidence of human immunodeficiency virus (HIV antibody positive) infection at the
Screening Visit.
8. History of hypersensitivity to any ingredient contained in the study intervention.
9. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to
the Screening Visit.
10. Evidence of hepatitis B (positive hepatitis surface antigen [HBsAg] or positive core
antibody [anti-HBc]) with negative surface antibody [anti-HBs] or hepatitis C viral
infection (HCV antibody positive, except for patients with documented successful
treatment and documented sustained virologic response [SVR]) at Screening.
11. History of malignancy within 5 years of the Screening Visit, with the exception of
nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no
evidence of recurrence.
12. History of persistent or recurrent infections prior to the Screening Visit.
13. Active systemic bacterial, viral, or fungal infection within 14 days prior to study
intervention administration on Day 1.
14. Presence of fever as documented by a temperature ≥ 38°C (100.4°F) within 7 days prior
to administration of study intervention on Day 1.
15. History or presence of any risk factors for Torsades de Pointes (eg, heart
failure/cardiomyopathy or family history of Long QT Syndrome), a screening QT interval
corrected using Fridericia's formula (QTcF) > 450 msec for males and > 470 msec for
females, or receiving medications known to significantly increase the QTc.
16. Laboratory abnormalities at the Screening Visit, including:
a. Alanine aminotransferase > 2 × the upper limit of normal (ULN)
b. Direct bilirubin > 2 × ULN
17. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 and/or are on dialysis.
18. Any other clinically significant laboratory abnormality that, in the opinion of the
Investigator, would make the participant inappropriate for the study or put the participant
at undue risk.