ALXN2420 Versus Placebo in Combination With Somatostatin Analogs in Participants With Acromegaly

Inclusion Criteria:

• Documented diagnosis of acromegaly, that is, historically documented evidence of aGH-secreting pituitary adenoma based on MRI or pathology report

• Must be receiving maximum, or maximally tolerated dose per treating physicianjudgment, of long-acting SSAs (octreotide or lanreotide LAR) and meet both of thefollowing:

1. Received for ≥ 6 months prior to screening

2. Receiving a once-monthly regimen (approximately every 4 weeks). Note:participants on stable regimens of other durations (for example, every 3 or 6weeks) are not eligible

• Must be a partial responder to SSAs defined as > 20% relative IGF 1 reduction duringthe course of SSA therapy

• Serum IGF-1 levels > 1.3 to 5*ULN inclusive, as assessed at a central laboratory andadjusted for age and sex, based on average of 2 consecutive values obtained duringthe Screening Period and obtained ≥ 7 days apart

Exclusion Criteria:

• Had surgery for pituitary adenoma within the last 6 months before Day 1 or planningto receive surgery for pituitary adenoma during the study

• Pituitary adenoma that, per Investigator's judgment, is worsening as assessed bypituitary/sellar MRI or computed tomography scan obtained ≤ 6 months prior toscreening

• Pituitary adenoma causing compression of the chiasm

• Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatmentwith dopamine agonists

• Known hypothyroidism or hypocortisolism not adequately treated with a stable dose ofthyroid or glucocorticoid hormone replacement therapy for ≥ 3 months prior toScreening

• Active, clinically significant cardiac disease as judged by the Investigator

• History of unstable angina, stroke, or acute myocardial infarction ≤ 3 months priorto screening

• Known uncontrolled type 2 diabetes (HbA1c > 10%)

• Active malignant disease ≤ 2 years prior to screening with exception of basal andsquamous cell carcinoma of the skin

• Received any type of fractionated radiotherapy or a second surgical adenectomy forpituitary adenoma within the last 3 years (5 years for conventional radiation)before starting treatment and/or are planning to receive radiotherapy or a secondsurgical adenectomy during the study

• Received pegvisomant ≤ 8 weeks prior to screening

• Received dopamine agonists ≤ 4 weeks prior to screening

• Received pasireotide LAR ≤ 4 months prior to screening

• Clinically significant renal or hepatic disease at the time of screening, as judgedby the Investigator

• eGFR (CKD-EPI formula) < 30 mL/minute/1.73 m^2 documented based on recent value (< 3months prior to randomization)

• Clinically significant abnormal values for hematology, biochemistry, coagulation, orurinalysis, as judged by the Investigator, including, but not limited to, totalbilirubin > 1.5ULN (except if in free bilirubin linked to a known Gilbert Syndrome)or AST, ALT, or alkaline phosphatase > 2ULN