Tocilizumab for Painful Chronic Pancreatitis (TOPAC-trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aalborg University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

21 May 2024 → ongoing

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

We hypothesise that treatment with tocilizumab, compared with a placebo, will reduce symptom burden (CP-related pain) and improve physical functioning and quality of life in patients with CP.

Secondary objectives 1

1. In addition, we hypothesise that the clinical effects will be linked to a decrease in pancreatic inflammation and fibrosis as well as systemic inflammation. We also hypothesise that the pain-relieving effect of tocilizumab will lead to the normalisation of pain processing in CP patients.

Conditions and MedDRA coding

Chronic pancreatitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed informed consent
2. 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))
3. 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.
4. 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
5. Abdominal pain of presumed pancreatic origin (i.e., upper abdominal pain radiating to the back).
6. 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
7. ≥ 18 years of age
8. The participant must be able to read and understand the informed consent forms
9. The participant is willing and able to comply with the scheduled visits, treatment plan, and other trial procedures

Exclusion criteria 10

1. 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).
2. 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.
3. 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.
4. Active or recurrent infections.
5. 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).
6. Known hypersensitivity to Tocilizumab.
7. Severe liver disease, indicated by ALT with >5 upper normal limit.
8. Thrombocytopenia (platelet count < 50 x 109/L).
9. Neutropenia (neutrophil count <2 x 109/L).
10. Pregnancy, fertile women (<55 years) must provide a urine sample for pregnancy test upon inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome assessment parameter is the total score of the COMPAT-SF questionnaire (31). The primary endpoint is the difference between the tocilizumab and placebo-treated groups in the COMPAT-SF score after 24 weeks.

Secondary endpoints 7

1. The European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30) questionnaire between treatment groups (tocilizumab vs. placebo) at weeks 12 and 24.
2. The Brief Pain Inventory Short Form (mBPI-SF) pain severity and interference scores between treatment groups (tocilizumab vs. placebo) at weeks 12 and 24.
3. The average daily pain score (registered in the mBPI-SF) between treatment groups (tocilizumab vs. placebo) at week 24.
4. The Patient Global Impression of Change (PGIC) questionnaire between treatment groups (tocilizumab vs. placebo) at week 24.
5. The CP prognosis score (COPPS)-score between treatment groups (tocilizumab vs. placebo) at week 24.
6. Use of analgesics, including opioid-based therapies (type and dose).
7. Adherence to treatment and frequency of adverse events.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aalborg University Hospital

Sponsor organisation

Aalborg University Hospital

Address

Moelleparkvej 4

City

Aalborg

Postcode

9000

Country

Denmark

Scientific contact point

Organisation

Aalborg University Hospital

Contact name

Søren Schou Olesen

Public contact point

Organisation

Aalborg University Hospital

Contact name

Søren Schou Olesen

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications