ZUPREME-1 Phase 2b Trial of Petrelentide for Obesity Completes Enrollment
The amylin analog at 5 doses will be compared with placebo when added to a reduced calorie diet and increased physical activity regimen for 42 weeks, said Zealand Pharma.
The phase 2b ZUPREME-1 clinical trial that is evaluating the long-acting amylin analog petrelintide in individuals with overweight or obesity has enrolled the final participant, according to an announcement from developer Zealand Pharma.1
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The trial, which began in December 2024, has enrolled more than 480 participants and will evaluate 5 target doses of petrelentide up to 9 mg during a study period of 42 weeks, the company said. The study will assess the effects of once-weekly injectable petrelintide compared with placebo on body weight, safety, and tolerability in people with obesity or overweight with weight-related comorbidities.
During the randomized, double-blind, multinational trial, the 5 investigational doses of petrelentide will be compared with placebo when added to an intervention that follows a reduced-calorie diet and includes increased physical activity, Zealand said. The trial includes a screening phase, a dose-escalation period lasting up to 16 weeks, a maintenance period extending to week 42, and a follow-up phase through week 51.
The primary endpoint of ZUPREME-1 is the percentage change in body weight from baseline to week 28. Secondary endpoints include percentage change in body weight at week 42, change in waist circumference, and changes in metabolic measures, ie, hemoglobin A1c, high-sensitivity C-reactive protein, fasting lipids, and fasting glucose. The company has included a predetermined exploratory endpoint that will assess includes body composition changes at week 42, assessed by magnetic resonance imaging (MRI).
The long-acting amylin analog is formulated for subcutaneous administration once-a-week and has stable chemical and physical properties that Zealand said will support co-formulation with other peptides. Activation of amylin receptors is believed to induce weight reduction by restoring the body's sensitivity to leptin, increasing early satiety.2,3
Pre-clinical and clinical data suggest petrelintide may induce weight loss comparable to glucagon-like peptide-1 receptor agonists, potentially with improved tolerability, the company stated.
"We are excited to announce the rapid completion of enrollment and randomization in the Phase 2b ZUPREME-1 clinical trial with petrelintide in people with overweight or obesity, just three months after initiation," David Kendall, MD, Zealand Pharma chief medical officer said in the press announcement. "This achievement reflects both the strong interest in amylin agonists from the clinical community and highlights the importance of developing new treatment options that can leverage distinct mechanisms of action to better serve those living with overweight and obesity."
According to the announcement, Zealand remains on track to initiate a second trial of petrelentide. The phase 2b ZUPREME-2 trial, which will launch in the first half of 2025, is designed to evaluate petrelintide in individuals with overweight or obesity and type 2 diabetes.
