The primary objective of this study is to evaluate the efficacy of 15-week treatment with ALXN2420 versus placebo for decreasing insulin-like growth factor IGF-1 levels, when administered in combination with somatostatin analog (SSA) therapy to adult participants with acromegaly.

Inclusion Criteria:

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

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

  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 6 weeks) are not eligible

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

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

Exclusion Criteria:

• Had surgery for pituitary adenoma within the last 6 months before Day 1 or planning to receive surgery for pituitary adenoma during the study
• Pituitary adenoma that, per Investigator's judgment, is worsening as assessed by pituitary/sellar MRI or computed tomography scan obtained ≤ 6 months prior to screening
• Pituitary adenoma causing compression of the chiasm
• Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment with dopamine agonists
• Known hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or glucocorticoid hormone replacement therapy for ≥ 3 months prior to Screening
• Active, clinically significant cardiac disease as judged by the Investigator
• History of unstable angina, stroke, or acute myocardial infarction ≤ 3 months prior to screening
• Known uncontrolled type 2 diabetes (HbA1c > 10%)
• Active malignant disease ≤ 2 years prior to screening with exception of basal and squamous cell carcinoma of the skin
• Received any type of fractionated radiotherapy or a second surgical adenectomy for pituitary adenoma within the last 3 years (5 years for conventional radiation) before starting treatment and/or are planning to receive radiotherapy or a second surgical 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 judged by the Investigator
• eGFR (CKD-EPI formula) < 30 mL/minute/1.73 m^2 documented based on recent value (< 3 months prior to randomization)
• Clinically significant abnormal values for hematology, biochemistry, coagulation, or urinalysis, as judged by the Investigator, including, but not limited to, total bilirubin > 1.5*ULN (except if in free bilirubin linked to a known Gilbert Syndrome) or AST, ALT, or alkaline phosphatase > 2*ULN

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.