Treg Immunotherapy in Crohn's Disease

NCT03185000 | Unknown Phase 1 DMC

• 1 other identifier: TRIBUTE Feasibility
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

• Rate of dose-limiting toxicities (DLTs)

  Pre-defined safety events occurring within 5 weeks post-infusion

  One period will be assessed, from Week 0 to Week 5

Secondary Outcomes (4)

• Disease Activity Score (CDAI / PRO-2) calculated by evaluation of patient's diary completion and colonoscopy findings

  CDAI / PRO-2 scores will be calculated at Week 0, Week 8, Week 21

• Biomarkers analysis (CRP, FCP) measured by blood test and stool sample analysis

  CRP and FCP will be measured throughout the study, from Week 0 to Week 21

• Mucosal Healing Score (SES-CD) calculated by evaluation of colonoscopy findings

  SES-CD scores will be calculated at screening and week 8

• Description of non-DLT adverse events

  Week 0 to 5 and beyond week 5

Other Outcomes (8)

• Analysis of lymphocyte populations circulating in blood as well as localised in the intestinal lamina propria

  Translational research samples will be collected at Week 1, 2, 3, 5, 9, 10, 11, 13, 16, 21

• Cytokine levels in blood and in intestinal lamina propria

  Translational research samples will be collected at Week 1, 2, 3, 5, 8,16, 21

• Comparison of circulating and localised cells to determine differences and similarities

  Translational research samples will be collected at Week 1, 2, 3, 5, 8,16, 21

Study Arms (1)

Immediate ATIMP (AP)

EXPERIMENTAL

Patients will receive Treg immunotherapy (TR004) infusion at Week 0.

Drug: TR004 (Treg immunotherapy)

Interventions

TR004 (Treg immunotherapy) DRUG

Administered Intravenously (IV)

Also known as: Autologous regulatory T cells (Tregs) expanded in vitro

Immediate ATIMP (AP)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide written informed consent and able to comply with the protocol requirements
• Male or female aged between 18 and 80 (inclusive) years of age at date of consent
• A diagnosis of Crohn's disease (CD) established ≥12 weeks prior to date of consent by standard clinical, radiological, endoscopic and histological criteria
• Documented moderate-to-severe CD with a Crohn's Disease Activity Index (CDAI) \>= 220 within 3 months of date of consent
• Active CD (mucosal inflammation) including ulceration, as assessed by colonoscopy at screening
• Failure to tolerate or to respond 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
• Stable doses of concomitant medications
• Normal or non-clinically significant electrocardiogram (ECG), as assessed by the Investigator at screening
• Negative serology for HIV, Hepatitis B (cAb and sAg), Hepatitis C, HTLV and Syphilis at screening
• Subject is judged by the principal investigator to be in otherwise good health based upon the results of all screening investigations in combination with medical history and physical examination

You may not qualify if:

• A diagnosis of ulcerative colitis or IBD-unclassified
• CD treatment-naïve patients, defined as patients who have never received or have refused standard CD treatment
• History of clinically significant drug or alcohol abuse in the last 12 months prior to date of consent
• Any history of major immune deficiency disorder, except Crohn's disease
• Patients with a history of pulmonary embolism or deep vein thrombosis. Current or recent history (within 1 year prior to screening) of major organ or system failure or condition, acute or chronic that in the opinion of the investigator should preclude enrollment, except Crohn's disease
• History of intestinal resection or intra-abdominal surgery within 6 months prior to date of consent
• 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
• Patients with ileostomy or colostomy
• Patients with short bowel syndrome (less than 1.5m of small bowel)
• Complication of Crohn's disease such as strictures/stenosis, penetrating disease, or any other manifestation that might require surgery.
• Patient has received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to date of consent and/or during the screening period
• 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)
• 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.
• Current medically significant infection i.e. infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to date of consent or oral anti-infectives for non-Crohn's disease related infections within 14 days prior to screening visit
• Subject with an active systemic viral infection or any active viral infection that based on the investigator's clinical assessment makes the patient unsuitable for the study

Sponsors & Collaborators

• King's College London: lead
• Guy's and St Thomas' NHS Foundation Trust: collaborator
• Medical Research Council: collaborator
• St. George's Hospital, London: collaborator
• Miltenyi biotech: collaborator

Study Sites (1)

Guy's Hospital - Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

Related Publications (3)

• Canavan JB, Scotta C, Vossenkamper A, Goldberg R, Elder MJ, Shoval I, Marks E, Stolarczyk E, Lo JW, Powell N, Fazekasova H, Irving PM, Sanderson JD, Howard JK, Yagel S, Afzali B, MacDonald TT, Hernandez-Fuentes MP, Shpigel NY, Lombardi G, Lord GM. Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease. Gut. 2016 Apr;65(4):584-94. doi: 10.1136/gutjnl-2014-306919. Epub 2015 Feb 24.

  PMID: 25715355 BACKGROUND

• Rodger B, Clough J, Vasconcelos J, Canavan JB, Macallan D, Prevost AT, Lord GM, Irving P. Protocol for a first-in-human feasibility study of T regulatory cells (TR004) for inflammatory bowel disease using (ex vivo) Treg expansion (TRIBUTE). BMJ Open. 2025 Jan 23;15(1):e092733. doi: 10.1136/bmjopen-2024-092733.

  PMID: 39855667 DERIVED

• Goldberg R, Scotta C, Cooper D, Nissim-Eliraz E, Nir E, Tasker S, Irving PM, Sanderson J, Lavender P, Ibrahim F, Corcoran J, Prevost T, Shpigel NY, Marelli-Berg F, Lombardi G, Lord GM. Correction of Defective T-Regulatory Cells From Patients With Crohn's Disease by Ex Vivo Ligation of Retinoic Acid Receptor-alpha. Gastroenterology. 2019 May;156(6):1775-1787. doi: 10.1053/j.gastro.2019.01.025. Epub 2019 Jan 30.

  PMID: 30710527 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Crohn Disease

Interventions

In Vitro Techniques

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Peter Irving, Dr

  King's College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Irving, Dr

CONTACT

+44 20 7188 2499; peter.irving@gstt.nhs.uk

Joanne Palmer Joyce

CONTACT

joanne.palmerjoyce@gstt.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: June 14, 2017
• Study Start: August 8, 2022
• Primary Completion: March 31, 2024
• Study Completion: June 30, 2025
• Last Updated: January 31, 2023

Record last verified: 2023-01

Locations

GB (1)