OXTEND-03
Research type
Research Study
Full title
A Phase 3 randomized 3-arm trial (double-blind Debio 4126, placebo control, and open-label Debio 4126), to assess the efficacy and safety of Debio 4126, a 12-week octreotide formulation, in patients with acromegaly previously treated with somatostatin analogs
IRAS ID
1011515
Contact name
Sophie Larnaudie
Contact email
Sponsor organisation
Debiopharm International S.A.
Eudract number
2024-516616-24
Research summary
This is a randomized, 3-arm placebo-controlled trial of Debio 4126, in patients with acromegaly who are receiving a stable dose of octreotide or lanreotide and have a hormone in the blood called insulin-like growth factor 1 (IGF-1) at levels not higher than the normal range. Acromegaly is a rare chronic disorder that affects individuals of all racial groups and ages, typically being diagnosed between 40-50 years old, with a slightly higher prevalence in women than in men. This condition is characterized by the excessive secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), primarily caused by a benign pituitary GH-secreting adenoma in over 95% of cases.
The overproduction of GH and IGF-1 leads to increased cellular proliferation and differentiation, resulting in tissue remodeling, organ enlargement (organomegaly), and metabolic disturbances. Diagnosis of acromegaly involves clinical examination and biochemical assessments, with patients often experiencing abnormal growth of bone and soft tissue, as well as dysregulated glucose metabolism, increasing their risk for cardiovascular disease and mortality.
Given the chronic and potentially life-threatening nature of acromegaly, treatment is necessary for nearly all patients. Options include surgery as the first-line therapy, medical interventions, or pituitary radiation in cases where other treatments have been ineffective. The goal of treatment is to achieve a normal range of IGF-1 levels for the patient's age, as normalization of IGF-1 is considered the most crucial biochemical marker for diagnosing and assessing treatment success.
Octreotide and lanreotide are currently the preferred medical treatments for managing GH and IGF-1 levels and reducing pituitary tumour volume. These medications have shown efficacy as both adjuvant and first-line therapies.
Octreotide, the first synthetic SSA approved by the FDA in 1988, was initially available as an immediate-release formulation for subcutaneous injection every 8 to 12 hours. Since 1998, a long-acting release formulation has been available for intramuscular injection every 4 weeks. In 2020, an oral formulation of octreotide was introduced for twice-daily dosing. Octreotide's structure includes amino acids essential for receptor binding, with a high affinity for SSTR2.
Pharmacologically, octreotide acts similarly to SST, inhibiting GH, glucagon, and insulin. It has been shown to significantly reduce GH and/or IGF-1 levels in patients with acromegaly, often leading to normalization of these hormone levels.
Debio 4126 is a 12-week extended-release octreotide formulation, meaning it has a slow release in the body, which is expected to maintain a low level of IGF-1 for a period of 12 weeks.
The trial will consist of 3 parallel arms:
• Arm A – double-blind Debio 4126 treatment, followed by open-label Debio 4126 treatment
• Arm B – double-blind placebo treatment, followed by open-label Debio 4126 treatment
• Arm C – open-label Debio 4126 treatment
Double-blind means that no one will know which treatment is administered. Open-label means that everybody will know that they receive the study drug. A placebo treatment has no therapeutic effect but it looks like the trial drug and is administered in the same way.REC name
South Central - Oxford B Research Ethics Committee
REC reference
25/SC/0074
Date of REC Opinion
14 Apr 2025
REC opinion
Further Information Favourable Opinion