Autoimmune Hemolytic AnemiaPhase 2NCT07190261
A Single-arm Phase 2 Prospective Clinical Study of Enatumab in the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia
A Phase 2 study testing enatumab in people with Autoimmune Hemolytic Anemia, run by Bing Han at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Autoimmune Hemolytic Anemia
- What is being tested?
- enatumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteChina
- Study dates
- 18 Sep 2025to 18 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years old, gender not limited.
- Primary wAIHA with a clear diagnosis.
- Patients who have relapsed or are refractory after at least second-line treatment (previous treatments include at least two types of glucocorticoids, CD20 monoclonal antibodies or other immunosuppressants). Refractory is defined as failure to achieve partial remission after 6 months of treatment with a stable dose of immunosuppressants.
- The infusion of CD20 monoclonal antibody should be at least three months apart. If taking immunosuppressants such as cyclosporine and sirolimus, the medication should be discontinued for at least one month.
- Hemoglobin (HGB) ≤100g/ and ≥ 60g/L.
- Before treatment, the patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were less than 3 times the upper limit of normal (ULN), and the serum creatinine was less than 1.5 times ULN.
- Voluntarily join this study, sign the informed consent form with good compliance, and be willing to cooperate with regular follow-ups for efficacy evaluation and side effect monitoring.
Who cannot join
- (1) Those with impaired functions of organs such as the heart, liver and lungs; Patients with acute renal insufficiency.
- Patients with connective tissue diseases and other secondary AIHA. (3) There is an active infection of hepatitis B virus (HBV), hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), human immunodeficiency virus (HIV), or any uncontrolled bacterial, fungal or viral infection.
- Complicated with malignant tumors or a history of tumors. (5) When screening, the subjects had other types of uncorrected anemia, such as nutritional anemia, etc.
- Had received other BCMA-targeted or CART treatments before screening. (7) Pregnant or lactating women. (8) Activity ≥ grade 2 peripheral sensory/motor neuropathy. (9) Had received treatment with other experimental drugs within 30 days (or as required by local regulations) or within 5 half-lives (whichever is longer) prior to the first use of the intervention drug in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Peking union medical college hospital
Beijing, Shuangfuyuan, NO I., 100730
Bing Han, +86-010-69155760, hanbing_li@sina.com
About this study
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.
Read the 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.
- Conditions
- Autoimmune Hemolytic Anemia
- Being tested
- enatumab
- Keywords
- Autoimmune Hemolytic Anemia, Enatumab, Single-arm phase 2 prospective
- Medical subject headings
- Anemia, Hemolytic, Autoimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enatumabDrug
The recommended subcutaneous injection dose of this product is as follows: an incremental dose of 12mg on day 1, an incremental dose of 32mg on day 4, an initial treatment dose of 38mg on day 8, and subsequent treatment doses of 38mg in weeks 4 and 6.
| Study group | Role | What they receive |
|---|---|---|
| Enatumab treat | Experimental | The recommended subcutaneous injection dose of this product is as follows: an incremental dose of 12mg on day 1, an incremental dose of 32mg on day 4, an initial treatment dose of 38mg on day 8, and subsequent treatment doses of 38mg in weeks 4 and 6. Receives: Drug: enatumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall response rate (ORR)
The overall response rate (ORR) and complete response rate (CRR) at 3 months. The overall response rate (ORR) is defined as the ratio of patients achieving complete response (CR) plus partial response (PR)
Measured: 3 months
Secondary outcomes (1)
The incidence and severity of adverse events
Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.
Measured: 6-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2025
- Study start18 Sep 2025 (estimated)
- Primary completion18 Sep 2027 (estimated)
- Study completion18 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune Hemolytic AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bing Han
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bing Han, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07190261
- Sponsor's protocol ID
- BCMA/CD3+--R/R wAIHA
- Status last verified
- Sep 2025
- First submitted
- 17 Sep 2025
- Last updated
- 24 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: individual participant data would be accepted upon request
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm Phase 2 Prospective Clinical Study of Enatumab in the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia
- ClinicalTrials.gov ID
- NCT07190261
- Acronym / sponsor ID
- BCMA/CD3+--R/R wAIHA
- Conditions
- Autoimmune Hemolytic Anemia
- Keywords
- Autoimmune Hemolytic Anemia, Enatumab, Single-arm phase 2 prospective
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- Bing HanUniversity, hospital or other
- Study start
- 18 Sep 2025 (estimated)
- Primary completion
- 18 Sep 2027 (estimated)
- Study completion
- 18 Sep 2027 (estimated)
- First posted
- 24 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Enatumab treat | Experimental | Drug: enatumabThe recommended subcutaneous injection dose of this product is as follows: an incremental dose of 12mg on day 1, an incremental dose of 32mg on day 4, an initial treatment dose of 38mg on day 8, and subsequent treatment doses of 38mg in weeks 4 and 6. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 years old, gender not limited.
- Primary wAIHA with a clear diagnosis.
- Patients who have relapsed or are refractory after at least second-line treatment (previous treatments include at least two types of glucocorticoids, CD20 monoclonal antibodies or other immunosuppressants). Refractory is defined as failure to achieve partial remission after 6 months of treatment with a stable dose of immunosuppressants.
- The infusion of CD20 monoclonal antibody should be at least three months apart. If taking immunosuppressants such as cyclosporine and sirolimus, the medication should be discontinued for at least one month.
- Hemoglobin (HGB) ≤100g/ and ≥ 60g/L.
Key exclusion criteria (4 listed)
- (1) Those with impaired functions of organs such as the heart, liver and lungs; Patients with acute renal insufficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enatumabThe recommended subcutaneous injection dose of this product is as follows: an incremental dose of 12mg on day 1, an incremental dose of 32mg on day 4, an initial treatment dose of 38mg on day 8, and subsequent treatment doses of 38mg in weeks 4 and 6. | Drug | Enatumab treat |
Primary outcome
overall response rate (ORR)
Time frame: 3 months
The overall response rate (ORR) and complete response rate (CRR) at 3 months. The overall response rate (ORR) is defined as the ratio of patients achieving complete response (CR) plus partial response (PR)
1 secondary outcome
The incidence and severity of adverse events
Time frame: 6-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2025.
- Individual participant dataSharing planned: Yes. individual participant data would be accepted upon request
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Active, not recruitingPhase 1
CAR T-cell Therapy Targeting CD19 and BCMA in Patients With AIHA Who Have Failed ≥3 Lines of Therapy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing enatumab in people with Autoimmune Hemolytic Anemia, run by Bing Han at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall response rate (ORR) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2025.