BACKGROUND: Chronic pancreatitis (CP) is a fibro-inflammatory disease that damages the pancreas, leading to severe abdominal pain and metabolic complications. Activated macrophages and pancreatic stellate cells drive CP progression, and their activity is regulated by complex immune signals, including interleukin-6 (IL-6). Preclinical studies suggest that blocking IL-6 signalling may have pain-relieving effects in CP. Based on these findings, we hypothesise that tocilizumab, an anti-IL-6 receptor antibody, will reduce abdominal pain and improve physical functioning and quality of life in patients with CP. Additionally, we expect tocilizumab to decrease pancreatic inflammation, fibrosis, and systemic inflammation, as well as normalise pain processing. METHODS: The TOPAC trial is a phase 2, randomised, placebo-controlled, double-blinded, investigator-initiated trial conducted at Aalborg University Hospital, Denmark. Patients with painful CP and suspicion of sustained pancreatic inflammation (n = 36) will be randomised (1:1) to receive intravenous tocilizumab (8 mg/kg) or a corresponding placebo every 4 weeks for 24 weeks. The primary endpoint is the difference between the two groups in the change of the Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) score from baseline to 24 weeks. Secondary outcomes include questionnaires focused on quality of life, physical/daily functioning, and the severity of pain and its impact on functioning. Additionally, safety is a key secondary endpoint. Exploratory outcomes include soluble biomarkers of inflammation and fibrosis, multiparametric pancreatic magnetic resonance imaging, quantitative sensory testing and neurophysiological measurements of the pain processing. CONCLUSIONS: This placebo-controlled clinical trial aims to study the potential clinical benefits of blocking IL-6 signalling in painful CP.