UC
Conditions
Keywords
UC；CAR-T
Brief summary
A Single-Center, Open-Label, Single-Arm Exploratory Clinical Study on the Use of Autologous CAR-T Cell Therapy Injection for the Treatment of Refractory and Relapsing Ulcerative Colitis: A Preliminary Exploration of 12-Week Clinical Remission with Autologous CAR-T Cell Injection in Refractory and Relapsing Ulcerative Colitis.
Detailed description
The primary objective： Preliminary Exploration of 12-Week Clinical Remission with Autologous CAR-T Cell Injection for the Treatment of Refractory and Relapsing Ulcerative Colitis. The secondary objectives： Evaluate the 12-Week and 52-Week Clinical Response Rates, Endoscopic Parameters (Endoscopic Response Rate, Endoscopic Remission Rate, Mucosal Healing), Ultrasound and Imaging (Response Rate, Remission Rate), Improvement in Quality of Life, and Safety of Autologous CAR-T Cell Therapy Injection for the Treatment of Refractory and Relapsing Ulcerative Colitis.
Interventions
DRUGBCMA CAR-T or CD19 CAR-T or CD19×BCMA
Autologous BCMA/CD19/CD19×BCMA-targeting CAR T cells, dosage 1\*10\^6/kg, intravenous injection once
Sponsors
Hebei Senlang Biotechnology Inc., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* The subject or guardian must provide voluntary informed consent; * Diagnosis based on the "Chinese Guidelines for the Diagnosis and Treatment of Ulcerative Colitis (2023, Xi'an)": Patients diagnosed with UC (based on comprehensive evaluation including clinical, imaging, pathological, and endoscopic assessments), with a follow-up period of more than 3 months; * Moderate to severe active ulcerative colitis: Patients meeting the criteria of a clinical modified Mayo score of 6-12 points and an endoscopic Mayo score (ES) ≥ 2 points (within 10 days prior to baseline); * Previous treatments with all domestically approved medications for UC, including conventional immunosuppressive drugs, biologics, and small molecule drugs, have failed; * Hematological, liver and kidney function, cardiopulmonary function, and coagulation function meet specific criteria.
Exclusion criteria
* Women who are pregnant or lactating; * Any condition that, in the judgment of the Investigator, could increase the subject's risk or compromise the interpretation of the trial results; * Diagnosed with CD (Crohn's Disease) or indeterminate colitis (IBD-unclassified), or other types of colitis or enteritis that may confound efficacy assessment; * Currently diagnosed with fulminant colitis and/or toxic megacolon; * UC limited to the rectum; * Currently or likely to require colostomy or ileostomy; * Has previously undergone total proctocolectomy or partial colectomy. * Patients who test positive for hepatitis B surface antigen (HBsAg) should be excluded; if HBsAg is negative but hepatitis B core antibody (HBcAb) is positive, and peripheral blood HBV DNA is above the detection limit, they should be excluded; patients who test positive for hepatitis C virus (HCV) antibodies and HCV RNA should be excluded; patients who test positive for human immunodeficiency virus (HIV) antibodies; patients who test positive for cytomegalovirus (CMV) DNA; patients who test positive for Epstein-Barr virus (EBV) DNA; patients who test positive for both treponemal-specific antibodies and non-specific antibodies for syphilis should be excluded. * Any uncontrolled active infection present at the time of signing the ICF. * Subjects who have had severe, opportunistic, or chronic/recurrent extra-intestinal infections within 2 months prior to screening; evidence of active/infectious herpes zoster infection within 8 weeks prior to screening; active tuberculosis or latent tuberculosis infection present at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of CRS and ICANS | 28 days | Evaluate the occurrence of cytokine release syndrome and severe neurotoxic adverse events within 28 days after CAR-T cell infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| imaging response rate: 12 weeks and 52 weeks | 1 year | Radiologic response (CTE/MRE): Improvement in bowel wall thickness, mesenteric inflammatory fat, bowel wall blood flow, and bowel wall enhancement signal compared to baseline, with perianal fistula-related VAlinf \< 6. |
| imaging remission rate: 12 weeks and 52 weeks | 1year | Radiologic remission (CTE/MRE): Complete normalization of inflammatory parameters on bowel CTE or MRE, with perianal fistula-related VAlinf = 0. |
| Clinical response rate: 12 weeks and 52 weeks | 1 year | Clinical response (based on MMS): MMS decreases by ≥2 points and ≥30% from baseline, along with a reduction in RBS by ≥1 point or an RBS absolute value ≤1. |
| Clinical remission rate: 12 weeks and 52 weeks | 1 year | Clinical remission (based on MMS): ES is 0 or 1, no fragility, RBS is 0, and SFS is 0 or 1 and not greater than baseline. |
| Endoscopic mucosal healing rate: 12 weeks and 52 weeks | 1 year | No ulcers are observed on endoscopy. |
| Endoscopic response rate: 12 weeks and 52 weeks | 1 year | Endoscopic remission: ES = 0. |
| IBDQ score assessment | 1 year | IBDQ score. |
| Pharmacokinetic data parameters | 1 year | Analysis using CAR DNA copy number measured by qPCR; the highest concentration of CAR-T cells expanded in peripheral blood after administration. |
| level of IL-6 | 1 year | Pharmacodynamics data parameter |
| Pharmacodynamics data parameter | 1 year | CRP |
| Ferritin level | 1 year | Pharmacodynamics data parameters |
| Ultrasound remission rate: 12 weeks and 52 weeks | 1 year | Ultrasound remission: Normal bowel wallthickness (small intestine \<3mm, colon \<4mm, with no complications detectable by this method |
| Ultrasound response rate: 12 weeks and 52 weeks | 1 year | Ultrasound response: Reduction in bowel wall thickness (BWT) compared to baseline |
Countries
China
Contacts
CONTACTYingdi Chen
PRINCIPAL_INVESTIGATORJianping Wang
Foresea Life Insurance Guangzhou General Hospital
Outcome results
None listed