Efficacy and Safety Evaluation of ALXN2420 with Somatostatin Analogs in Adult Acromegaly: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2025-521243-20-00
- Protocol
- ALXN2420-Acro-201
- Sponsor
- Alexion Pharmaceuticals Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of 15 weeks of ALXN2420 treatment versus placebo in reducing IGF-1 levels when administered in combination with somatostatin analogs in adults with acromegaly. Secondary objectives include the assessment of:
- improvement in disease symptoms;
- impact on health-related quality of life;
- changes in global impression of severity and global impression of change.
Participants
This clinical trial involves 28 adult participants diagnosed with acromegaly. The study population includes both males and females, with ages ranging from 18 to 80 years. Eligible individuals must have a documented pituitary adenoma through magnetic resonance imaging or pathology. Participants are required to be receiving a once-monthly regimen of long-acting somatostatin analogues for at least 6 months at a maximum or maximally tolerated dose. Inclusion necessitates being a partial responder to these analogues, defined by a relative reduction in insulin-like growth factor 1 of more than 20%. Additionally, serum levels of IGF-1 must be between 1.3 and 5 times the upper limit of normal, as adjusted for age and sex.
Plans and Procedures
This Phase 2, randomized, double-blind, placebo-controlled, multicenter, dose range-finding study is designed to evaluate the efficacy, safety, and pharmacokinetics of ALXN2420, a growth hormone receptor antagonist, in combination with somatostatin analogs for the treatment of acromegaly. Participants will receive either ALXN2420 administered via subcutaneous injection or a matching placebo alongside background therapy. The primary objective is to assess the percentage change from baseline in serum IGF-1 levels after 15 weeks of treatment. The study includes a screening period to confirm eligibility, followed by a 15-week treatment period. Secondary endpoints include the number of participants achieving specific IGF-1 levels, changes in disease-specific symptoms and quality of life scores, and the assessment of treatment-emergent adverse events and antidrug antibodies. The overall trial duration is estimated to conclude by December 31, 2027.
Treatment
The experimental treatment consists of ALXN2420, a growth hormone receptor antagonist, provided as a solution for injection. This substance is administered via subcutaneous injection.
A matching placebo for ALXN2420 is utilized in the study design.
Background therapy includes somatostatin analogs. This regimen consists of octreotide acetate administered through intramuscular injection at a dose of 40 mg, or lanreotide acetate administered via subcutaneous route at a dose of 120 mg.
Efficacy
The efficacy of ALXN2420 in participants with acromegaly is assessed through several parameters at Week 15. The primary endpoint is the percentage change from baseline in serum IGF-1 level. Secondary efficacy assessments include the number of participants achieving serum IGF-1 levels ≤1.3 upper limit of normal (ULN) or ≤1.0 ULN. Additionally, changes from baseline are evaluated for symptoms using a disease specific questionnaire, 36-item Short Form Survey (SF-36) summary scores and subscores, EuroQol 5-Dimension 5-Level (EQ-5D-5L), and Acromegaly Quality of Life (AcroQoL).
Further assessment of clinical status includes the Patient Global Impression of Severity (PGIS) scale to measure the global impression of severity and the Patient Global Impression of Change (PGIC) scale to measure the global impression of change. These measures are all recorded at the 15-week timepoint following administration in combination with somatostatin analogs.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 1_Aged 18 to 80 years (inclusive) at Screening
- 2_Documented diagnosis of acromegaly, that is, historically documented evidence of a GH secreting pituitary adenoma based on MRI or pathology report
- 3_ Receiving maximum, or maximally tolerated dose per treating physician judgment, of long-acting SSAs and meet both of the following: - Received for ≥ 6 months prior to Screening - Receiving a once-monthly regimen (approximately every 4 weeks)
- 4_partial responder to SSAs at Screening, defined as > 20% relative IGF-1 reduction during the course of SSA therapy
- 5_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
- 1_Participants are excluded if they have any of the following medical conditions: 1. Had surgery for pituitary adenoma within the last 6 months before Day 1 or planning to receive surgery for pituitary adenoma during the study 2. Pituitary adenoma that, per Investigator’s judgement, is worsening as assessed by pituitary/sellar MRI or computed tomography scan obtained ≤ 6 months prior to Screening 3. Pituitary adenoma causing compression of the chiasm 4. Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment with dopamine agonists 5. Known hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or glucocorticoid hormone replacement therapy for ≥ 3 months prior to Screening 6. Active, clinically significant cardiac disease as judged by the Investigator 7. History of unstable angina, stroke, or acute myocardial infarction ≤ 3 months prior to Screening 8. Known uncontrolled Type 2 diabetes (HbA1c >10%) 9. Active malignant disease ≤ 2 years prior to Screening with exception of basal and squamous cell carcinoma of the skin
- 2_Participants are excluded in case of Clinically significant renal or hepatic disease at the time of Screening, as judged by the Investigator or: - eGFR (CKD-EPI formula) < 30 mL/minute/1.73 m2 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
- 3_Participants are excluded if received any of the following: - 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 - pegvisomant ≤ 8 weeks prior to Screening - dopamine agonists ≤ 4 weeks prior to Screening - pasireotide long-acting release ≤ 4 months prior to Screening
- 4_Known allergy or sensitivity to ALXN2420 or any of the excipients
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Recruiting | 01 Sept 2025 | 3 |
 Hungary | Not Recruiting | 01 Sept 2025 | 5 |
 Italy | Not Recruiting | 01 Sept 2025 | 8 |
 Lithuania | Not Recruiting | 01 Sept 2025 | 3 |
 The Netherlands | Not Recruiting | 01 Sept 2025 | — |
 Poland | Not Recruiting | 01 Sept 2025 | 4 |
 Romania | Not Recruiting | 01 Sept 2025 | 5 |
| Netherlands | — | — | 4 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ALXN2420 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 00 | 52 | PRD12432760 |
OCTREOTIDE ACETATE | Other | — | INTRAMUSCULAR | 40 | 52 | SUB03490MIG |
OCTREOTIDE ACETATE | Other | — | INTRAMUSCULAR | 40 | 52 | SUB03490MIG |
LANREOTIDE ACETATE | Other | — | SUBCUTANEOUS | 120 | 52 | SUB14326MIG |
LANREOTIDE ACETATE | Other | — | SUBCUTANEOUS | 120 | 52 | SUB14326MIG |
matching placebo for ALXN2420 | Placebo | N/A | — | — | — | N/A |
LANREOTIDE ACETATE | Other | — | SUBCUTANEOUS | 120 | 52 | SUB14326MIG |
OCTREOTIDE ACETATE | Other | — | INTRAMUSCULAR | 40 | 52 | SUB03490MIG |