Inflammatory Bowel Diseases (IBD)
Conditions
Keywords
Ulcerative Colitis, Crohn's disease, Inflammatory Bowel Disease, IBD, UC, CD, CAR-T, Cellular Therapy
Brief summary
This is a Phase I, IIa, Single-Arm, interventional, open label, treatment study to evaluate the safety and tolerability of ICG318 CAR-T (BCMA-CD19-IL-15/IL15sushi cCAR T cells) in patients with relapsed and/or refractory inflammatory bowel disease.
Detailed description
Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease of the gastrointestinal (GI) tract. IBD may result in GI lesions as well as extraintestinal manifestations affecting the joints, skin, eyes, and biliary system. IBD is driven by humoral immune cells including B cells, plasma cells and long-lived plasma cells. ICG318 CAR-T, the investigational agent in this clinical trial, is an armored, compound chimeric antigen receptor (cCAR) composed of two independently functioning CARs that target the CD19 surface antigen and the BCMA surface antigen on B cells and plasma/long-lived plasma cells, respectively. This study is being conducted to evaluate the safety and efficacy of ICG318 CAR-T in patients with refractory IBD. A single dose of ICG318 CAR-T will be evaluated after cyclophosphamide and fludarabine lymphodepletion.
Interventions
BIOLOGICALICG318, BCMA-CD19-IL-15/IL-15 sushi Compound CAR T
Anti-BCMA, Anti-CD19 Compound CAR-T cells
Sponsors
iCell Gene Therapeutics
iCAR Bio Therapeutics Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria: 1. All subjects or legal guardians must sign an ethics committee-approved informed consent form in writing prior to initiation of any screening procedures. 2. Male or female subject over 18 years old and under 70 years old at the time of evaluation; Weight ≥ 40 kg. 3. Diagnosed with inflammatory bowel disease assessed by the investigator and the disease course has been ≥ 3 months before signing informed consent (clinical manifestations, endoscopy and histopathological reports consistent with the diagnosis of inflammatory bowel disease are required). 4. The subject has documented inadequate response, loss of response, or intolerance to at least one advanced therapy for IBD. 5. Patients with IBD during the screening period need to meet the requirements of moderate to severe IBD; UC: active ulcerative colitis, defined as per the adapted Mayo score criteria. CD: CD subjects with moderate to severe active CD, defined as interpreted by SES-CD. 6. Life expectancy greater than 6 months; 7. Female individuals with fertility (defined as all females who are physiologically capable of becoming pregnant) must provide informed consent, have a negative blood pregnancy test result, and agree to use highly effective contraception from the time of informed consent until 1 year after CAR-T cell infusion. Male individuals with fertility must agree to use effective barrier contraception from the time of informed consent until 1 year after CAR-T cell infusion, and should not donate semen or sperm during the entire study period. 8. Indeterminate colitis is permitted. Key
Exclusion criteria
1. Subjects who have previously received any BCMA and/or CD19 targeted cell therapy products or CAR-T therapy for any target before signing the informed consent form. 2. Undiagnosed type colitis, fulminant colitis, Hirschsprung-associated enterocolitis (HAEC), microscopic colitis, ischemic colitis, radiation colitis, colitis-related diverticular disease, or other colitis or enteritis type that may confound the evaluation of efficacy. 3. Subjects with malignant tumors or dysplasia on endoscopy. 4. Subjects with severely impaired vital organ function. 5. Impaired bone marrow function. 6. Active hepatitis B, HCV positive, HIV antibody positive, Treponema pallidum antibody positive, Active tuberculosis. 7. Presence of any IBD related complications determined by the investigator to interfere with the study of ICG318 CAR-T in refractory IBD. 8. History of bleeding within 30 days determined by the investigator to exclude the patient. 9. Infectious diseases: subjects with acute, life-threatening bacterial, viral or fungal infections that have not been controlled. 10. Hospitalization for IBD-related complications within 30 days prior to screening. 11） Clinically significant central nervous system disease determined by the investigator to impair the subjects ability to participate safely in this trial. 12） Subjects with prior or concurrent malignancies. Exceptions may be determined at the discretion of the investigator. 13） Vaccination within 30 days before screening and vaccination within 3 months after planned cell ICG318 CAR-T infusion. 14） Subjects who are receiving or have received another investigational drug or drugs without adequate washout time as determined by the principal investigator. 15） Those who are judged by the investigator to be unfit for leukapheresis, or whose IBD disease severity and trajectory are not compatible with infusion with ICG318 CAR-T cells, or any critical steps of the trial evaluation such as but not limited to contraindications to colonoscopy. 16） Female subjects who are pregnant or lactating. 17） Autoimmune diseases judged by the investigator to require systemic treatment and affect the evaluation of efficacy. 18） Suicidal tendencies, tobacco use, substance use, or alcohol abuse as determined by the investigator. 19） Those who have a history of a severe drug allergy, or are allergic to the test drug ingredients, excipients or combined therapeutic drugs. 20） Other conditions that the investigator believes should not participate in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events (AEs) after ICG318 CAR-T infusion. | Starting day 0 and up to 2 years after ICG318 CAR-T infusion. | Number of participants with AEs, Serious Adverse Events (SAEs), Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESI), and Dose Limiting Toxicities (DLTs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the recommended phase 2 dose (RP2D) regimen. | Starting day 0 and assessed 2 years after ICG318 CAR-T infusion. | The protocol is based on cohort schema with dose escalation from 1×10\^6/kg to 4×10\^6/kg. |
| The proportion of subjects who achieved drug-free remission. | At 6 months, 12 months, 24 months after ICG318 CAR-T infusion. | Clinical, endoscopic, and histological remission maintained without any IBD-directed therapy. |
| Fecal calprotectin levels. | 28 days, 2 months, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months after ICG318 CAR-T infusion. | — |
| Cmax | Assessed as per schedule of events up to 2 years after ICG318 CAR-T infusion. | Maximum serum concentration of ICG318 CAR-T. |
| Tmax | Assessed as per schedule of events up to 2 years after ICG318 CAR-T infusion. | Time to maximum serum concentration of ICG318 CAR-T. |
| T1/2 | Assessed as per schedule of events up to 2 years after ICG318 CAR-T infusion. | Half-life of ICG318 CAR-T serum concentration. |
| AUC | Assessed as per schedule of events up to 2 years after ICG318 CAR-T infusion. | Plasma ICG318 CAR-T concentration versus time. Total systemic exposure to ICG318 CAR-T over time. |
| Rate of B cell elimination and naïve B-Cell recovery | Assessed as per schedule of events up to 2 years after ICG318 CAR-T infusion. | B cell subsets will be assessed by flow cytometry panels and B-Cell receptor sequencing. |
| Recovery of immunoglobulins | Assessed as per schedule of events up to 2 years after ICG318 CAR-T infusion. | Immunoglobulins IgG, IgM and IgA levels. |
| The proportion of subjects who achieved clinical remission from Crohn's Disease (CD) | 3 months, 6 months, 12 months, 18 months, 24 months after ICG318 CAR-T infusion. | CD activity index (CDAI) remission |
| The proportion of subjects who achieved clinical response from CD | 3 months, 6 months, 12 months, 18 months, 24 months after ICG318 CAR-T infusion. | CDAI reduction |
| The proportion of subjects who achieved endoscopic remission from CD | 12 months, 24 months after ICG318 CAR-T. | SES-CD remission. |
| The proportion of subjects who achieved endoscopic response from CD | 12 months, 24 months after ICG318 CAR-T. | SES-CD reduction |
| Histological Remission from CD | 12 months, 24 months after ICG318 CAR-T. | Absence of inflammation on tissue samples collected from endoscopic biopsy. |
| The proportion of subjects who achieved clinical remission from Ulcerative Colitis (UC) | 3 months, 6 months, 12 months, 18 months, 24 months after ICG318 CAR-T infusion. | Adapted Mayo score remission. |
| The proportion of subjects who achieved clinical response from UC | 3 months, 6 months, 12 months, 18 months, 24 months after ICG318 CAR-T infusion. | Adapted Mayo score response. |
| The proportion of subjects who achieved endoscopic remission from UC | 12 months, 24 months after ICG318 CAR-T infusion. | Mayo Endoscopic Subscore (MES) remission. |
| The proportion of subjects who achieved endoscopic response from UC | 12 months, 24 months after ICG318 CAR-T infusion. | MES response. |
| Histological remission from UC | 12 months, 24 months after ICG318 CAR-T infusion. | Nancy Histological Index (NHI) scoring. Evaluation performed on tissue samples collected from endoscopic biopsy. |
Countries
China
Contacts
CONTACTKevin Pinz, MS
Outcome results
None listed