Tocilizumab for treating pain in chronic pancreatitis

Tocilizumab for Painful Chronic Pancreatitis: A Randomised, Placebo-Controlled, Double-blinded, Investigator Initiated Trial (TOPAC Trial)

This study is testing if tocilizumab can help reduce pain and improve quality of life for people with chronic pancreatitis.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Aalborg University Hospital (other)
• Drugs / interventions: Tocilizumab
• Locations: 1 site (Aalborg, North Denmark)
• Trial ID: NCT06426160 on ClinicalTrials.gov

What this trial studies

This placebo-controlled study aims to evaluate the effects of tocilizumab, an anti-interleukin-6 receptor antibody, on symptom burden, physical functioning, and quality of life in patients suffering from chronic pancreatitis. The study is based on recent findings that highlight the role of IL-6 in the inflammatory processes associated with chronic pancreatitis. By inhibiting IL-6 signaling, the study seeks to provide a disease-modifying treatment that could alleviate pain and inflammation. This is the first placebo-controlled trial in humans to explore immune-modulating treatments for this condition.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals with a confirmed or probable diagnosis of chronic pancreatitis who experience significant pain.

Not a fit: Patients with conditions unrelated to chronic pancreatitis or those who do not meet the diagnostic criteria for the disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce pain and improve the quality of life for patients with chronic pancreatitis.

How similar studies have performed: While this approach is novel in humans, preclinical studies have shown promising results in targeting IL-6 signaling for chronic pancreatitis treatment.

Eligibility criteria

Inclusion Criteria:

* Signed informed consent.
* Probable or definitive diagnosis of CP according to the M-ANNHEIM criteria. This entails a typical clinical history of CP, including recurrent pancreatitis or abdominal pain in combination with the following additional criteria:
* A definitive diagnosis of CP is established by one or more of the following additional criteria:
* i) Pancreatic calcification
* ii) Moderate or marked ductal lesions (according to the Cambridge classification)
* iii) Exocrine pancreatic insufficiency, defined as pancreatic steatorrhea markedly reduced by enzyme supplementation
* iv) Histological verification of CP
* A probable diagnosis of CP is established by one or more of the following additional criteria:
* i) Mild ductal alterations (according to the Cambridge classification)
* ii) Recurrent or persistent pseudocysts
* iii) Pathological test of pancreatic exocrine function (such as faecal elastase-1 test, secretin test, secretin-pancreozymin test)
* iv) Diabetes mellitus
* Abdominal pain of presumed pancreatic origin (i.e., upper abdominal pain radiating to the back).
* Evidence of ongoing pancreatic inflammatory activity, with an inflammatory pancreatic flare occurring one or more times within the past six months. An inflammatory pancreatic flare is defined as an exacerbation of pancreatic pain in combination with one or more of the following criteria:
* i) Plasma amylase levels elevated 2-fold or more than the participant's usual amylase level.
* ii) Elevated plasma levels of CRP 2-fold the upper normal level without suspicion of other sources such as infection.
* iii) Signs of pancreatic inflammation on cross-sectional imaging.
* ≥ 18 years of age
* The participant must be able to read and understand the informed consent forms.
* The participant is willing and able to comply with the scheduled visits, treatment plan, and other trial procedures.

Exclusion Criteria:

* End-stage CP indicated by severe pancreatic atrophy defined as segmented pancreas volume \<20 ml on the latest available cross-sectional imaging examination (Computed Tomography (CT) or MRI).
* Pancreatic duct obstruction by a stricture and/or stone amendable to endoscopic or surgical treatment. Patients with previous pancreatic duct decompression procedures are allowed to participate.
* Ongoing alcohol or substance abuse. The patient must document abstinence from alcohol and substance abuse for the preceding six months prior to study enrolment. Recreational alcohol consumption within the safety limits recommended by the National Danish Health Authorities (i.e., max. ten units of alcohol per week) is allowed.
* Active or recurrent infections.
* Untreated ulcers in the gastrointestinal tract (however, those who have undergone proper treatment and one month has elapsed with no recurrence of symptoms will not be excluded).
* Known hypersensitivity to Tocilizumab.
* Positive test for Tuberculosis during screening
* Positive test for Hepatitis during screening
* Severe liver disease, indicated by ALT with \>5 upper normal limits.
* Thrombocytopenia (platelet count \< 50 x 109/L).
* Neutropenia (neutrophil count \<2 x 109/L).
* Pregnancy and no contraception use, fertile women (\<55 years) must provide a urine sample for pregnancy test upon inclusion.

Where this trial is running

Aalborg, North Denmark

• Centre for Pancreatic Diseases and Mech-Sense research laboratory, Aalborg University Hospital — Aalborg, North Denmark, Denmark (RECRUITING)

Study contacts

• Principal investigator: Søren S Olesen, MD, Ph.D. — Mech-Sense, Department of Gastroenterology, Aalborg University Hospital
• Study coordinator: Rasmus Hagn-Meincke, MD

Conditions: Pancreatitis, Chronic, Inflammation, Pancreatic diseases, Digestive System Diseases