ALXN2420 Versus Placebo in Combination With Somatostatin Analogs in Participants With Acromegaly (ASTERIA)

Alexion Pharmaceuticals

Status and phase: Begins enrollment in 1 month; Phase 2

Conditions: Acromegaly

Treatments: Drug: ALXN2420; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07037420

D7890C00001

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 3 patient groups, including a placebo group

ALXN2420

Experimental group

Description:

During the Primary Evaluation Period, participants will receive the first dose of ALXN2420 via SC injection on Day 1, followed by daily administration thereafter for a total of 15 weeks.

Treatment:

Drug: ALXN2420

Placebo

Placebo Comparator group

Description:

During the Primary Evaluation Period, participants will receive the first dose of placebo via SC injection on Day 1, followed by daily administration thereafter for a total of 15 weeks.

Treatment:

Drug: Placebo

Open-label Extension Period

Experimental group

Description:

During the Open-label Extension (OLE) Period, participants in the ALXN2420 treatment groups will continue receiving ALXN2420 treatment and participants in the placebo groups will crossover to receive ALXN2420 at Week 15. At the Week 15 Visit, the dose level and the dosing regimen of ALXN2420 will be determined for each participant based on the Week 13 IGF-1 level. The OLE Period assessments will be performed at Weeks 19, 26, 32, 39, 45, and 52.

Treatment:

Drug: ALXN2420