Complex perianal fistula in inactive/mildly active intraluminal Crohn's disease
Conditions
Interventions
Group 1 (Dose escalation):Conventional therapy + administration of 4x10000000 cells
Group 2 (Dose escalation):Conventional therapy + administration of 12x10000000 cells
Group 3 (Dose escalation):Conventional therapy + administration of 16x10000000 cells
Group 1 (Expansion stage):Administration is based on conventional treatment, and dosage is determined according to the results of dose escalation stage
Group 2 (Expansion stage):Administration is based on conventional treatment, and dosage is determined according to the results of dose escalation stage
Placebo group:Placebo injection (acellular active ingredient) on the basis of conventional treatment
Sponsors
The Sixth Affiliated Hospital of Sun Yat-Sen University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >18 years, with good general health, no gender limit; 2. Those diagnosed with Crohn's disease according to WHO criteria, the time of diagnosis is not less than 6 months; 3. According to the AGA classification method or Parks classification method, the diagnosis of complex Crohn's disease anal fistula, and the number of external orifices =2; 4. Patients judged to be inactive/mildly active, that is, CDAI scale evaluation <220; 5. Patients who do not respond well to standard therapy, including those who have been treated with at least one of the following standard therapies (to the antibiotics ciprofloxacin, metronidazole, immunomodulators, or anti-TNF therapy) without or insufficient response (not seen partial or complete closure of the fistula, or the development of a new fistula during induction therapy), diminished efficacy (recurrence of a fully closed fistula during maintenance therapy, or worsening of a partially closed fistula during maintenance therapy), or intolerance (regardless of duration of dosing) , or patients with anal fistula in Crohn's disease who must stop treatment due to unacceptable side effects); Standard therapy includes: (1) Received the antibiotic ciprofloxacin or metronidazole for at least 4 weeks; (2) Receive immunosuppressive therapy (such as azathioprine, 6-mercaptopurine, methotrexate, etc.) for at least 12 weeks; (3) Received anti-TNF drugs (including infliximab, adalimumab, certolizumab, polyethylene glycol, etc.) for at least 12 weeks; (4) Received anti-IL-12/23 therapy (ustekinumab) for at least 16 weeks; (5) Received the anti-integrin drug vedolizumab for at least 14 weeks and natalizumab for at least 12 weeks; 6. Voluntarily sign the informed consent and abide by the relevant rules and regulations.
Exclusion criteria
Exclusion criteria: 1. Severe proctitis or dominant active bowel disease requiring immediate treatment through colonoscopy; 2. Patients with abscess effusion larger than 2 cm and did not receive drainage treatment within 2-3 weeks before enrollment; 3. Patients with rectal or anal stenosis, artificial anus, rectovaginal fistula, common anal fistula or enterocutaneous fistula; 4. Patients who require surgery in the perianal region for reasons other than fistulas at the time of enrollment, or patients who are expected to require such surgery in this region within 26 weeks of enrollment; 5. Patients who have received or are receiving steroid therapy within 4 weeks before receiving treatment; 6. Patients who have received cell therapy in the past; 7. Patients who are allergic to test drugs or excipients and possible impurities (penicillin, streptomycin, amphotericin B, recombinant trypsin, DMSO); 8. Patients who cannot undergo radiological examinations: anesthesia intolerance or contraindications to MRI scanning (eg, pacemaker, hip replacement or severe claustrophobia, hypersensitivity to gadolinium, etc.); 9. Patients with malignant tumors (except basal cell carcinoma or skin squamous cell carcinoma), or patients with a history of malignant tumors (except that the tumor disease has been in remission in the past 5 years); 10. Those who have cardiopulmonary disease and the investigator thinks that it is too severe to participate in the trial; 11. Those who suffer from any other type of medical or mental illness and the investigator considers unsuitable to participate in the trial; 12. Patients with congenital or acquired immunodeficiency (human immunodeficiency virus antibody HIV-Ab positive) or hepatitis B surface antigen HbsAg, hepatitis C virus antibody HCV-Ab, syphilis specific antibody TP-Ab results positive; 13. Serum creatinine >= 1.5 times the upper limit of normal, creatinine clearance rate = 1.5 times the upper limit of normal, AST or ALT greater than 2.5 times the upper limit of normal; 14. Patients who have undergone major surgery or severe trauma within the past 6 months; 15. Those who have a history of alcoholism within 6 months before screening; 16. Pregnant, breastfeeding patients or patients who do not agree to use non-drug contraception during the trial; 17. Patients deemed unsuitable for participation in this clinical trial by other investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Combined response rate;MRI fistula healing rate;Decreased number of draining fistulas;Fistula closure rate;Recurrence rate;Perianal Disease Activity Index PDAI;Crohn's Disease Activity Index CDAI;Quality of Life Analysis in Patients with Inflammatory Bowel Disease (IBDQ Scale);Adverse events (AE, SAE);Vital signs;Physical examination;Laboratory tests;12-lead ECG; | — |
Countries
China
Contacts
Public ContactWu Xiaojian
Outcome results
None listed