Acromegaly
Conditions
Keywords
Acromegaly, ALXN2420, Somatostatin Analog, insulin-like growth factor 1, IGF-1, SSA therapy, GHRA, Growth Hormone Receptor Antagonist
Brief summary
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.
Interventions
DRUGALXN2420
ALXN2420 will be administered via subcutaneous (SC) injection
DRUGPlacebo
Placebo will be administered via SC injection.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage Change From Baseline in Serum IGF-1 Level at Week 15 | Baseline, Week 15 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Who Achieve Serum IGF-1 Level ≤1.3 Upper Limit of Normal (ULN) at Week 15 | Week 15 |
| Number of Participants Who Achieve of Serum IGF-1 Level ≤1.0 ULN at Week 15 | Week 15 |
| Change from Basline in Symptoms as assessed by disease specific questionnaire, at Week 15 | Baseline, Week 15 |
| Change From Baseline in Serum IGF-1 Level at Week 15 | Baseline, Week 15 |
| Change From Baseline in 36-item Short Form Survey (SF-36) Summary Scores and Subscores at Week 15 | Baseline, Week 15 |
| Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) at Week 15 | Baseline, Week 15 |
| Change From Baseline in Acromegaly Quality of Life (AcroQoL) at Week 15 | Baseline, Week 15 |
| Change From Baseline in Global Impression of Severity at Week 15 as Assessed by Patient Global Impression of Severity (PGIS) Scale | Baseline, Week 15 |
| Global Impression of Change at Week 15 as Assessed by Patient Global Impression of Change (PGIC) Scale | Week 15 |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Study Intervention Discontinuation or Interruption | Baseline (Day 1) through Week 15 |
| Plasma Concentration of ALXN2420 | Baseline (Day 1) through Week 15 |
| Number of Participants With Antidrug Antibodies (ADAs) | Baseline (Day 1) through Week 15 |
Countries
Italy, Lithuania, Romania, United States
Outcome results
None listed