Octreotide subcutaneous depot for acromegaly: A randomized, double-blind, placebo-controlled phase 3 trial, ACROINNOVA 1

Abstract

Context: Acromegaly, characterized by excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1), impacts quality of life (QoL) and mortality. Standard of care (SoC; octreotide long-acting repeatable or lanreotide autogel) treatment typically requires healthcare provider administration. CAM2029, a novel subcutaneous octreotide depot with increased bioavailability using FluidCrystal technology, enables self-administration and room-temperature storage.

Objective: Assess superiority of CAM2029 versus placebo for biochemical control in patients with controlled acromegaly.

Design: 24-week, multinational, randomized, double-blind, phase 3 trial (NCT04076462).

Setting: 45 sites; ten countries.

Patients: 72 patients on SoC with biochemical control at screening (IGF-1 ≤upper limit of normal [ULN]; mean GH <2.5 μg/L).

Interventions: Patients were randomized 2:1 to once-monthly CAM2029 (n=48) or placebo (n=24).

Main outcome measures: Primary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24 mean), with dose-reduced patients classified as non-responders; first key secondary endpoint was the same, including dose-reduced responders. Second key secondary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24) and mean GH <2.5 μg/L (Week 24).

Results: At Week 22/24 (intention-to-treat analysis), CAM2029-treated patients demonstrated superior response rates versus placebo for IGF-1 (72.2% versus 37.5%; risk difference: 34.6, 95% confidence interval: 11.3, 57.9; p=0.0018), and combined IGF-1/GH (70.0% versus 37.5%; p=0.0035). CAM2029-treated patients had well-controlled symptoms, improved QoL and treatment satisfaction versus placebo and baseline. CAM2029 was well tolerated; safety was consistent with SoC.

Conclusions: CAM2029 provides a convenient and effective treatment option for acromegaly, with superior biochemical control versus placebo. Symptom control, QoL and satisfaction were improved from baseline SoC.

Keywords: CAM2029; FluidCrystal; acromegaly; octreotide; randomized controlled trial; somatostatin receptor ligands.