Evaluation of Tocilizumab in the Management of Painful Chronic Pancreatitis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
- Trial ID
- 2023-510084-35-00
- Sponsor
- Aalborg University Hospital
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy of **tocilizumab** in reducing symptom burden, specifically chronic pancreatitis (CP)-related pain, and improving physical functioning and quality of life in patients with CP, compared to a placebo. This is clinically relevant as chronic pancreatitis is a debilitating condition characterized by persistent pain and impaired quality of life, and current treatment options are limited.
Secondary objectives include assessing whether the clinical effects of tocilizumab are associated with a decrease in pancreatic inflammation and fibrosis, as well as systemic inflammation. Additionally, the study aims to determine if the pain-relieving effect of tocilizumab leads to the normalization of pain processing in CP patients.
Participants
The clinical trial involves participants diagnosed with **chronic pancreatitis**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a probable or definitive diagnosis of chronic pancreatitis according to the M-ANNHEIM criteria, which includes a typical clinical history of the disease. The trial does not involve a vulnerable population. Participants must be able to read and understand informed consent forms and be willing to comply with scheduled visits and trial procedures. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **tocilizumab** in reducing symptom burden and improving physical functioning and quality of life in patients with **chronic pancreatitis**. This is a randomized, double-blind, placebo-controlled trial, conducted over a period of 24 weeks. Participants will be randomly assigned to receive either tocilizumab or a placebo, with the primary endpoint being the difference in the COMPAT-SF score between the two groups after 24 weeks. Secondary endpoints include assessments using the EORTC-QLQ-C30 questionnaire, the Brief Pain Inventory Short Form, and the Patient Global Impression of Change, among others.
The trial will commence with an inclusion (screening) visit, where participants will be evaluated against the inclusion criteria, which include a probable or definitive diagnosis of chronic pancreatitis according to the M-ANNHEIM criteria, and the ability to comply with trial procedures. Following successful screening, participants will undergo baseline assessments before randomization. Study visits will occur at regular intervals, including key follow-up visits at weeks 12 and 24, to monitor treatment adherence, collect data on pain scores, quality of life, and any adverse events. The end-of-study visit will coincide with the final assessment at week 24.
Participant involvement is expected to last for the entire 24-week duration of the trial. However, conditions that may lead to early termination from the study include non-compliance with the treatment regimen, withdrawal of consent, or the occurrence of significant adverse events. The trial is set to begin recruitment in March 2024, with an estimated completion date in March 2027. The trial is categorized as a Phase 4 therapeutic exploratory and confirmatory clinical trial, not classified as low intervention.
Treatment
The clinical trial involves the administration of two primary treatments. The first treatment is **RoActemra**, a **tocilizumab**-based medication, which is provided as a 20 mg/mL concentrate for solution for infusion. This pharmaceutical form is specifically designed for **intravenous infusion**. The maximum daily dose is set at 25.57 mg/kg, with a total maximum dose of 800 mg per treatment cycle. The treatment period is limited to a maximum of 24 weeks. Tocilizumab is a protein-based active substance, and its administration is monitored to ensure compliance with the dosing schedule. The product is manufactured by Roche Registration GmbH and is authorized under the marketing authorization number EU/1/08/492/005.
The second treatment used in the trial is **Natriumklorid "B. Braun"**, which contains **sodium chloride** as the active substance. This is provided in the form of a solution for injection/infusion, suitable for administration via **infusion**. The maximum daily dose is 100 mL, with a total maximum dose of 100 mL per treatment cycle, also over a period of up to 24 weeks. Sodium chloride is a chemically derived substance, and its administration is similarly monitored to ensure adherence to the prescribed dosing regimen. This product is manufactured by B. Braun Melsungen AG and is authorized in Denmark under the marketing authorization number 13341.
In this trial, **tocilizumab** serves as the experimental treatment, while **sodium chloride** acts as the comparator or placebo treatment. Both treatments are administered under controlled conditions to evaluate the efficacy of tocilizumab in reducing symptom burden and improving quality of life in patients with chronic pancreatitis. Participant compliance is closely monitored throughout the trial to ensure the integrity of the study results.
Efficacy
Efficacy in the clinical trial titled "Tocilizumab for Painful Chronic Pancreatitis: A Randomised, Placebo-controlled, Double-blinded, Investigator-initiated Trial (TOPAC trial)" will be assessed using both primary and secondary endpoints. The primary endpoint is the total score of the COMPAT-SF questionnaire, with the primary outcome being the difference in this score between the tocilizumab and placebo-treated groups after 24 weeks. This assessment will provide a measure of the overall symptom burden related to chronic pancreatitis.
Secondary endpoints include several validated instruments and measures to evaluate various aspects of patient health and treatment impact. These include the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30) questionnaire, the Brief Pain Inventory Short Form (mBPI-SF) for pain severity and interference scores, and the Patient Global Impression of Change (PGIC) questionnaire. These assessments will be conducted at weeks 12 and 24 to compare the treatment groups. Additionally, the average daily pain score, CP prognosis score (COPPS), use of analgesics, adherence to treatment, and frequency of adverse events will be evaluated at specified time points, particularly at week 24.
Inclusion and Exclusion 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 (specific details for definitive (New ID 3) and for probable (New ID 4))
- 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, and/or (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), and/or (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 of 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, and/or (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 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.
- Severe liver disease, indicated by ALT with >5 upper normal limit.
- Thrombocytopenia (platelet count < 50 x 109/L).
- Neutropenia (neutrophil count <2 x 109/L).
- Pregnancy, fertile women (<55 years) must provide a urine sample for pregnancy test upon inclusion.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Recruiting | 01 Mar 2024 | 36 |
Sites & Investigators
Research sites
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Natriumklorid ”B. Braun” | Placebo | SOLUTION FOR INJECTION/INFUSION | INFUSION | 100 | 24 | PRD563912 |
RoActemra 20 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 25.57 | 24 | PRD2154624 |