Ignite Creation Date:
2025-12-24 @ 12:32 PM
Ignite Modification Date:
2025-12-29 @ 12:27 AM
Study NCT ID:
NCT07190261
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-09-24
First Post:
2025-09-17
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Single-arm Phase 2 Prospective Clinical Study of Enatumab in the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia
Sponsor:
Bing Han
Organization:
Study Overview
Official Title:
A Single-arm Phase 2 Prospective Clinical Study of Enatumab in the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-09
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:
None
Brief Summary:
Glucocorticoids are the first-line treatment for wAIHA, but patients are prone to recurrence after dose reduction or discontinuation of glucocorticoids. Birgens et al. 's study found that approximately 55% of patients treated with prednisolone monotherapy experienced recurrence at 36 months. The overall response rate of second-line treatment with rituximab is 70-80%, but the recurrence rate reaches 50%. The response rates of other immunosuppressants, such as cyclosporine, cyclophosphamide, and azathioprine, are relatively low, approximately 30-50%. Patients with chronic hemolysis have recurrent episodes, which affect their survival and quality of life. New treatment methods need to be explored.
Detailed Description:
Enatumab (BCMA/CD3 bispecific antibody) is a bispecific T-cell articulation antibody targeting BCMA. Its Fab segment can bind to BCMA of plasma cells, plasma blasts and multiple myeloma cells as well as CD3 of T cells. It has shown good efficacy in the treatment of relapsed/refractory multiple myeloma (MM). Enatumab can specifically bind to BCMA on myeloma cells and CD3 on T cells. Through the production and release of cytokines, it activates T cells, promotes T cell proliferation, and releases cytotoxic molecules (including granzyme and perforin), thereby inducing apoptosis of myeloma cells. Plasma cells play a significant role in the pathogenesis of autoimmune diseases and are the main cells that produce autoantibodies. In AIHA, the production of autoantibodies is closely related to the abnormal activation and proliferation of plasma cells. These autoantibodies attack red blood cells, leading to hemolysis. Therefore, theoretically speaking, enatumab may improve the condition of patients with AIHA by inhibiting or eliminating abnormal plasma cells and reducing the production of autoantibodies. At present, there have been two reports internationally on the treatment of refractory AIHA with T-cell agonists targeting BCMA. In 2025, Shi Jun et al. reported two cases where BCAM-targeted T-cell agonists (CM336) successfully treated relapsed AIHA after chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19. Patient 1 (a 10-year-old girl), with a 9-year history of Evans syndrome, still experienced recurrent hemolysis after multiple immunosuppressive treatments. Remission occurred within 14 days after the first CAR-T therapy, but recurred after 6.8 months. There was no response to the second CAR-T. Partial remission was achieved on the 13th day of CM336 treatment, and hemoglobin returned to normal on the 17th day. Case 2 (a 22-year-old female), with a 2-year history of AIHA, had no response to three immunosuppressants and splenectomy. She achieved remission within 10 days after CD19 CAR-T treatment and relapsed after 8.1 months. Partial remission was achieved on the 19th day of CM336 treatment, and hemoglobin returned to normal on the 21st day. The hemolytic indicators such as reticulocytes, LDH and indirect bilirubin in 2 patients decreased significantly and maintained remission for at least 6 months. The B cells and free light chains in the peripheral blood of the two patients decreased rapidly within 2 weeks after medication, and the B cells and plasma cells in the bone marrow were significantly cleared within 12 weeks. In terms of adverse reactions, Patient 1 developed grade 1 skin induration, and both patients presented with hypogammaglobulinemia. However, the overall safety was controllable. CM336 can effectively eliminate residual BCMA⁺ plasma cells, reverse the recurrence of multiple refractory AIHA after CAR-T, and provide a more targeted plasma cell-targeted immune strategy.
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?:
True
Is an FDA AA801 Violation?: