Ignite Creation Date:
2025-12-24 @ 1:57 PM
Ignite Modification Date:
2025-12-28 @ 5:03 AM
Study NCT ID:
NCT06475495
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-26
First Post:
2024-06-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis
Sponsor:
Charite University, Berlin, Germany
Organization:
Study Overview
Official Title:
Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis. Two-stage Interventional, Prospective, Randomized, Controlled, Open Label, Parallel-group Phase I/II Trial in Patients With Active, ACPA-positive and Treatment Refractory Rheumatoid Arthritis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COMPARE
Brief Summary:
The goal of this phase I/II clinical trial is to compare B-cell depletion by rituximab and anti-CD 19 CAR-T therapy in patients with rheumatoid arthritis. The main questions it aims to answer are:
* To assess the safety of anti-CD19 CAR T cell therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-I)
* To assess the safety of anti-CD19 CAR T cell therapy and of rituximab in subjects with active, ACPA positive and treatment refractory RA (Phase-II)
* To assess ACPA seroconversion after anti-CD19 CAR T cell or rituximab therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-II)
Participants in the test-arm will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR T-cell immunotherapy. In the comparator group patients will receive 2x1 g Rituximab i.v.
Follow-up time (both arms) is 52 weeks with regular visits at the site.
* To assess the safety of anti-CD19 CAR T cell therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-I)
* To assess the safety of anti-CD19 CAR T cell therapy and of rituximab in subjects with active, ACPA positive and treatment refractory RA (Phase-II)
* To assess ACPA seroconversion after anti-CD19 CAR T cell or rituximab therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-II)
Participants in the test-arm will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR T-cell immunotherapy. In the comparator group patients will receive 2x1 g Rituximab i.v.
Follow-up time (both arms) is 52 weeks with regular visits at the site.
Detailed Description:
This study aims to investigate the use of either rituximab as an established therapy or KYV101 (a fully human anti-CD19 CAR T cell therapy) in ACPA-positive RA patients who are refractory to previous treatments. This study is designed to determine and compare (i) the safety of these two B-cell targeted therapies, (ii) their clinical efficacy, (iii) their impact on the immunological status of the patient and in particular on ACPA positivity, and (iv) their ability to induce long-term (deep) clinical and molecular remission and drug-free survival.
The investigational product (IMP), KYV-101, is an autologous fully-human anti-CD19 CAR T-cell immunotherapy. . Before IMP infusion, patients will receive a premedication of 4 mg Dimetindenmaleat iv or equivalent antihistamine and 1000 mg oral acetaminophene. Prophylactic doses of acyclovir of 400mg 2x daily as well as cotrimoxazole 960mg 3x weekly will be administered orally following CAR T cell infusion until week 24. Tocilizumab 8mg/kg will be administered intravenously when required for treatment of IMP-related cytokine release syndrome. Dexamethasone as needed will be administered intravenously when required for treatment of neurological adverse event (ICANS).
In the control arm in phase II, rituximab will be administered. Rituximab, a chimeric monoclonal antibody targeting CD20, induces B cell depletion and is authorized for treatment of RA. A dose of 1000 mg will be administered intravenously at baseline and at day 14 as per summary of product characteristics. The need for further courses will be evaluated 24 weeks after baseline where retreatment of 1000 mg rituximab may be initiated if residual disease activity remains.
Follow-up time (both arms) is 52 weeks with regular visits at the site.
The investigational product (IMP), KYV-101, is an autologous fully-human anti-CD19 CAR T-cell immunotherapy. . Before IMP infusion, patients will receive a premedication of 4 mg Dimetindenmaleat iv or equivalent antihistamine and 1000 mg oral acetaminophene. Prophylactic doses of acyclovir of 400mg 2x daily as well as cotrimoxazole 960mg 3x weekly will be administered orally following CAR T cell infusion until week 24. Tocilizumab 8mg/kg will be administered intravenously when required for treatment of IMP-related cytokine release syndrome. Dexamethasone as needed will be administered intravenously when required for treatment of neurological adverse event (ICANS).
In the control arm in phase II, rituximab will be administered. Rituximab, a chimeric monoclonal antibody targeting CD20, induces B cell depletion and is authorized for treatment of RA. A dose of 1000 mg will be administered intravenously at baseline and at day 14 as per summary of product characteristics. The need for further courses will be evaluated 24 weeks after baseline where retreatment of 1000 mg rituximab may be initiated if residual disease activity remains.
Follow-up time (both arms) is 52 weeks with regular visits at the site.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2024-514955-13-00 | CTIS | None | View |