Treg Immunotherapy in Crohn's Disease — TRIBUTE  

Crohn Disease Clinical Trial

Official title: A First in Human Feasibility Study of T Regulatory Cells (TR004) for Inflammatory Bowel Disease Using (ex Vivo) Treg Expansion

Status Recruiting

Clinical Trial Summary

Crohn's Disease (CD) is a condition that causes inflammation of the digestive system or gut. Crohn's can affect any part of the gut, though the most common area affected is the end of the ileum (the last part of the small intestine), or the colon.

Crohn's is a chronic condition. This means that it is ongoing and life-long, although patients may have periods of good health (remission), as well as times when symptoms are more active (relapses or flare-ups).

Current available therapies frequently fail to maintain long-term remission and may be complicated by significant side effects.

There is an unmet medical need for novel therapies. Cellular therapies are emerging as potentially attractive therapeutic strategies.

The TRIBUTE trial will use autologous regulatory T cells (Tregs) expanded in vitro.

It is hoped that the administration of this treatment to patients with active CD will change the immune responses in the gut and reduce bowel wall inflammation.

Clinical Trial Description

The TRIBUTE trial is looking at a new type of treatment for Crohn's Disease (CD), called regulatory T-cells (Tregs) immunotherapy.

Regulatory T-cells are naturally produced by the immune system. These cells have a powerful immunosuppressive action; they prevent auto-immune diseases by suppressing the over-active response that the immune system mounts against the body in these diseases. In addition it is thought that in patients with active CD, other immune cells in the gut are resistant to the normal controlling action of Tregs. Finally, we have found that Tregs that are isolated from patients and then are grown in the laboratory are more suppressive than Tregs freshly isolated from patients' blood.

Treg immunotherapy, TR004, will be unique to each patient. White blood cells will be extracted from their blood via leukapheresis. These cells will form the starting material to manufacture TR004 by expansion in a GMP accredited laboratory following a validated manufacturing process.

It will take approximately 23 days to produce enough cells for the immunotherapy treatment.

The trial aims to recruit a total of 4 patients diagnosed with moderate to severe CD. Men and women aged over 18 years who did not tolerate or did not respond to at least 2 standard treatments for the condition will be eligible to participate.

TRIBUTE is an open label first in human feasibility study of a single dose of TR004. Four participants will receive a single dose of TR004. Participants will be dosed singly. Safety data will be collected for five weeks post administration and reviewed by the DSMB before proceeding to dose the next participant. All participants will be followed up to week 21 to collect further safety and exploratory efficacy data, with additional safety monitoring at 1 and 2 years post dose. There is one dose level - 3.0 - 5.0 million TR004/kg.

Participants will be involved in the study for up to 24 months, from screening to safety follow-up at Week 104.

Eligible participants will receive one TR004 infusion at Week 0.

Patients will have a number of blood tests over the course of the trial. This will allow the doctors to monitor how safe TR004 is and how the body reacts to it.

Other tests, including vital signs such as blood pressure, heart rate and temperature, stool testing, and colonoscopy/biopsy will also be performed for this purpose and participants will have regular check-ups by the trial team. Scans such as CT scans, MRI scans or ultrasounds may be performed prior to starting the trial and participants will fill out questionnaires and diaries to monitor their progress over the course of the trial.

There are currently no known benefits to the participants in taking part in the study. While it is hoped that the treatment will reduce bowel inflammation, this may not happen. Participants may not directly benefit from taking part in this study but the information gained from their participation may help to improve the treatments available to other people with Crohn's Disease.

During the blood tests participants may experience discomfort and there is a risk of bleeding and bruising around the puncture site but this is very rarely serious.

During leukapheresis and on infusion day cannulas will be inserted in participant's veins. The cannula insertion may cause pain, bruising, or, on rare occasions, infection.

Some people find the leukapheresis uncomfortable due to having to stay in the same position for 2-3 hours. Blood calcium level may fall during the procedure and this can cause numbness and tingling in hands and feet and around the mouth. Patients can also feel cold, dizzy or sick.

A colonoscopy poses few risks. Rarely, complications of a colonoscopy may include:

• Reaction to the sedative used during the test

• Bleeding from the site where the tissue sample (biopsy) is taken

• A tear in the colon or rectum wall (perforation). The risk of this is less than 1 in 1,000.

This is the first time this particular expanded Tregs treatment will be tested in human so there may be potential unknown risks that could be serious. The anticipated risks of Treg administration are similar to those of a blood transfusion. The potential risks are likely to be lower because the cells infused will be the patient's own cells rather than cells from a blood donor. Common transfusion symptoms include a red, itchy skin rash, swelling of the hands, arms, feet, ankles and legs, dizziness and headaches. Less common symptoms include high temperature, chills and shivering.

The TRIBUTE study will be set-up and run at Guy's and St Thomas NHS Foundation Trust, London. It will be the only UK centre recruiting participants into the study. ;

Related Conditions & MeSH terms

• Crohn Disease

• NCT number: NCT03185000
• Study type: Interventional
• Source: King's College London
• Contact: Peter Irving, Dr
• Phone: +44 20 7188 2499
• Email: peter.irving@gstt.nhs.uk
• Status: Recruiting
• Phase: Phase 1
• Start date: August 8, 2022
• Completion date: June 30, 2025