A first-in-human feasibility study of T regulatory cells (TR004) for inflammatory bowel disease using (ex vivo) Treg expansion
Crohn's Disease
Current interventions as of 01/12/2022: 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. Patients randomised to AP will receive TR004 at Week 0 and Placebo at Week 8. Patients allocated to PA will receive Placebo at Week 0 and TR004 at Week 8. There will be 3 dose levels for TR004: 0.5 – 1.0 x 10^6 TR004/kg, 3.0 – 5.0 x 10^6 TR004/kg and 8.0 – 10.0 x 10^6 TR004/kg. The first pair on the trial will be dosed at 0.5 – 1.0 x 10^6 TR004/kg. The CRM algorithm program will allocate dose levels for subsequent pairs. The information will be reviewed during the DSMB meetings in order to agree on the dose level for the next pairs. Both TR004 and Placebo will be administered intravenously over 30 minutes maximum. On dosing days, patients will be closely monitored. Blood tests and vital signs will be taken at specific time points throughout the day. At Week 8, patients will also have a colonoscopy and biopsy. Patients will be discharged from the hospital the day after dosing unless there are any safety concerns. Patients will then attend outpatient follow-up visits at Weeks 1, 2, 3, 5, 9, 10, 11, 13, 16, 21 and 52 (safety FUP). During these visits, patients will be reviewed by a doctor who will examine them and asks questions about how they have been feeling, any events/reactions they may want to report or any changes in their regular medications. Clinical and research blood tests will be taken to monitor safety following the infusions and potential response to treatment. Blood pressure, heart rate, oxygen saturation, temperature and weight will be measured to monitor safety. Stool samples will be collected in order to measure in
Current participant inclusion criteria as of 01/12/2022: 1. Able and willing to provide written informed consent and able to comply with the protocol requirements 2. Male or female aged between 18 and 80 (inclusive) years of age at the date of consent 3. A diagnosis of Crohn’s disease (CD) established ≥12 weeks prior to the date of consent by standard clinical, radiological, endoscopic and histological criteria 4. Documented moderate to severe CD with a Crohn’s Disease Activity Index (CDAI) 220 within 3 months of the date of consent 5. Active CD (mucosal inflammation) including ulceration, as assessed by colonoscopy at screening 6. Failure to tolerate or to respond, or lose response to at least 2 prior lines of standard CD medication intended to induce or maintain remission, as determined by the referring gastroenterologist. Examples of such medications include, but are not limited to, azathioprine, mercaptopurine, methotrexate, vedolizumab, ustekinumab or anti-tumour necrosis factor antibody therapy. This does not include steroids and 5-ASA medications 7. Stable doses of concomitant medications, as defined in Section 5.6 8. Normal or non-clinically significant electrocardiogram (ECG), as assessed by the Investigator at screening 9. Negative stool test for Clostridium difficile and faecal culture for standard pathogens at screening. For non-pathogenic organism, inclusion will be at the discretion of the Principal Investigator (PI). 10. Negative serology for HIV – 1/2, Hepatitis B (cAb and sAg), Hepatitis C, HTLV and Syphilis at screening 11. Patient is judged by the Chief Investigator to be in otherwise good health based upon the results of all screening investigations in combination with medical history and physical examination Previous participant inclusion criteria: 1. Able and willing to provide written informed consent and able to comply with the protocol requirements 2. Male or female aged between 18 and 80 (inclusive) years of age 3. A diagnosis of Cr
Current participant exclusion criteria as of 01/12/2022: 1. A diagnosis of ulcerative colitis or IBD-unclassified 2. CD treatment-naïve patients, defined as patients who have never received or have refused standard CD treatment 3. History of clinically significant drug or alcohol abuse in the last 12 months prior to the date of consent 4. Any history of major immune deficiency disorder, except Crohn’s disease 5. Patients with a history of pulmonary embolism or deep vein thrombosis. Current or recent history (within 1 year prior to screening) of a major organ or system failure or condition, acute or chronic that in the opinion of the investigator should preclude enrolment, except Crohn’s disease 6. History of intestinal resection or intra-abdominal surgery within 6 months prior to the date of consent 7. Requirement for immediate or imminent surgical, endoscopic or radiological intervention for indications including (but not limited to) toxic megacolon, obstruction, massive haemorrhage, perforation, sepsis, or intra-abdominal or perianal abscess 8. Patients with ileostomy or colostomy 9. Patients with short bowel syndrome (less than 1.5m of the small bowel) 10. Complications of Crohn’s disease such as strictures/stenosis, penetrating disease, or any other condition that might require gastrointestinal surgery 11. Patients receiving therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to the date of consent and/or during the screening period 12. Patients who are currently using anticoagulants including but not limited to warfarin, heparin, enoxaparin, dabigatran, apixaban, rivaroxaban (note that anti-platelet agents such as aspirin up to 325mg daily or clopidogrel are permitted) 13. Use of corticosteroids on the day of leukapheresis sampling, prior to the procedure Dosing should be delayed until after the procedure has been completed. This must be checked prior to the appointment and rescheduled if use is confirmed. 14. Current medi