Treg Immunotherapy in Crohn's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 6 February 2023
• Main ID: NCT03185000
• Date of registration: 13/04/2017
• Prospective Registration: Yes
• Primary sponsor: King's College London
• Public title: Treg Immunotherapy in Crohn's Disease TRIBUTE
• Scientific title: A First in Human Feasibility Study of T Regulatory Cells (TR004) for Inflammatory Bowel Disease Using (ex Vivo) Treg Expansion
• Date of first enrolment: August 8, 2022
• Target sample size: 4
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03185000
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: Peter Irving, Dr
• Affiliation: King's College London

• Name: Peter Irving, Dr

Key inclusion & exclusion criteria

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 at date of consent

3. A diagnosis of Crohn's disease (CD) established =12 weeks prior to 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 date of consent

5. Active CD (mucosal inflammation) including ulceration, as assessed by colonoscopy at
screening

6. 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

7. Stable doses of concomitant medications

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, Hepatitis B (cAb and sAg), Hepatitis C, HTLV and Syphilis
at screening

11. 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

Exclusion Criteria:

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
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 major organ or system failure or
condition, acute or chronic that in the opinion of the investigator should preclude
enrollment, except Crohn's disease

6. History of intestinal resection or intra-abdominal surgery within 6 months prior to
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 small bowel)

10. Complication of Crohn's disease such as strictures/stenosis, penetrating disease, or
any other manifestation that might require surgery.

11. 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

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 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

15. 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

16. History of tuberculosis (TB), unless there is documented evidence of completion of a
full course of anti-TB treatment prior to screening. For patients with latent TB, as
defined by a physician specialised in TB, they must have received prophylactic
treatment for 4 weeks minimum prior to dosing

17. History of moderate to severe congestive heart failure (NYHA class III or IV), recent
cerebrovascular accident (within 6 months of screening) and any other condition which,
in the opinion of the investigator, would put the subject at risk by participation in
the study

18. Subject with a previous history (within 12 months of consent) of dysplasia of the
gastrointestinal tract, or found to have dysplasia in any biopsy performed during the
screening endoscopy unless this is deemed to be a sporadic adenoma and has been
completely removed

19. Significant laboratory abnormalities:

Hb < 100g/L or WBC < 3.5 x 109/L or Plt < 100 x 109/L Creatinine > 1.5x ULN Total
bilirubin > 34 µmol/L or ALT > 2x ULN or GGT > 2xULN. Elevated unconjugated bilirubin
related to Gilbert's syndrome is allowed

20. Anti-TNF or ustekinumab therapy within 8 weeks of study dosing (day 0). Vedolizumab
therapy within 5 half-lives (15 weeks) of dosing. Exposure to cyclosporine or
tacrolimus within 2 weeks of date of consent

21. Patient currently receiving total parenteral nutrition (TPN) or plan to receive TPN at
any time during the course of the study

22. Received another investigational drug within 60 days of anticipated study date of
consent or 5 half lives whichever is greater

23. Patient who previously received stem cell transplantation

24. Current evidence of dysplasia or history of malignancy within the last 5 years of date
of consent (except successfully treated squamous cell or basal cell carcinoma, without
metastases or localised carcinoma in situ of the cervix)

25. Pregnant and lactating patients (females of childbearing potential with a positive
serum pregnancy test at screening visit 1 or day -1 at week 0)

26. Female patients of childbearing potential (i.e. not post-menopausal or surgically
sterilised) who are not willing to use effective methods of contraception (included
but not limited to hormonal contraception, Intrauterine devices, sexual abstinence,
vasectomised partner) to prevent


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn Disease

Intervention(s)

Drug: TR004 (Treg immunotherapy)

Primary Outcome(s)

Rate of dose-limiting toxicities (DLTs) [Time Frame: One period will be assessed, from Week 0 to Week 5]

Secondary Outcome(s)

Mucosal Healing Score (SES-CD) calculated by evaluation of colonoscopy findings [Time Frame: SES-CD scores will be calculated at screening and week 8]

Description of non-DLT adverse events [Time Frame: Week 0 to 5 and beyond week 5]

Disease Activity Score (CDAI / PRO-2) calculated by evaluation of patient's diary completion and colonoscopy findings [Time Frame: 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 [Time Frame: CRP and FCP will be measured throughout the study, from Week 0 to Week 21]

Secondary ID(s)

TRIBUTE Feasibility

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Miltenyi biotech

Guy's and St Thomas' NHS Foundation Trust

Medical Research Council

St. George's Hospital, London