Treg Immunotherapy in Crohn’s Disease
- Conditions
- Crohn's DiseaseDigestive System
- Registration Number
- ISRCTN97547683
- Lead Sponsor
- King's College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 4
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 Crohn’s disease (CD) established =3 months prior to 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 screening
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 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, 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
12. Clinical Blood Tests prior to dosing, assessed on Day-1 at Week 0 and Week
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 medically significant infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to consent or oral anti-infectives for non-Crohn’s disease-related infections within 14 days prior to consent
15. Participants 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 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 patient at risk by participating in the study
18. Patient with a previous history (within 12 months of the consent) of dysplasia of the gastrointestinal tract, or found to have dysplasia during the screening endoscopy unless this is deemed to be a sporadic adenoma and has been completely removed
19. Significant laboratory abnormalities, assessed on Day-1 at Week 0:
19.1. Hb < 100g/L or WBC < 3.5 x 109/L or Plt < 100 x 109/L
19.2. Creatinine > 1.5x ULN
19.3. Total bilirubin > 34 µmol/L or ALT > 2x ULN or GGT > 2xULN. Elevated unconjugated bilirubin related to Gilbert’s syndrome
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Current primary outcome measure as of 01/12/2022:Number of dose-limiting toxicities measured using the criteria defined in the protocol for 24 hours post-dosing, and at weeks 1, 2, 3 and 5 safety follow-up visitsPrevious primary outcome measures:1. Rate of dose limiting toxicities (DLTs) occurring 5 weeks post-infusions – two periods will be assessed, from Week 0 to Week 5 and from Week 8 to Week 132. Determination of Maximum Tolerated Dose (MTD), defined as the dose associated with a target DLT rate of 25%, is assessed by recording the rate of DLTs occurring between W0 and W5 and between W8 and W13
- Secondary Outcome Measures
Name Time Method